Search results for: accelerated pathways

Authors: M. D. Haneef, R. B. Randall, Z. Peng

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Journal bearings used in IC engines are prone to premature failures and are likely to fail earlier than the rated life due to highly impulsive and unstable operating conditions and frequent starts/stops. Vibration signature extraction and wear debris analysis techniques are prevalent in the industry for condition monitoring of rotary machinery. However, both techniques involve a great deal of technical expertise, time and cost. Limited literature is available on the application of these techniques for fault detection in reciprocating machinery, due to the complex nature of impact forces that confounds the extraction of fault signals for vibration based analysis and wear prediction. This work is an extension of a previous study, in which an engine simulation model was developed using a MATLAB/SIMULINK program, whereby the engine parameters used in the simulation were obtained experimentally from a Toyota 3SFE 2.0 litre petrol engines. Simulated hydrodynamic bearing forces were used to estimate vibrations signals and envelope analysis was carried out to analyze the effect of speed, load and clearance on the vibration response. Three different loads 50/80/110 N-m, three different speeds 1500/2000/3000 rpm, and three different clearances, i.e., normal, 2 times and 4 times the normal clearance were simulated to examine the effect of wear on bearing forces. The magnitude of the squared envelope of the generated vibration signals though not affected by load, but was observed to rise significantly with increasing speed and clearance indicating the likelihood of augmented wear. In the present study, the simulation model was extended further to investigate the bearing wear behavior, resulting as a consequence of different operating conditions, to complement the vibration analysis. In the current simulation, the dynamics of the engine was established first, based on which the hydrodynamic journal bearing forces were evaluated by numerical solution of the Reynold’s equation. Also, the essential outputs of interest in this study, critical to determine wear rates are the tangential velocity and oil film thickness between the journal and bearing sleeve, which if not maintained appropriately, have a detrimental effect on the bearing performance. Archard’s wear prediction model was used in the simulation to calculate the wear rate of bearings with specific location information as all determinative parameters were obtained with reference to crank rotation. Oil film thickness obtained from the model was used as a criterion to determine if the lubrication is sufficient to prevent contact between the journal and bearing thus causing accelerated wear. A limiting value of 1 µm was used as the minimum oil film thickness needed to prevent contact. The increased wear rate with growing severity of operating conditions is analogous and comparable to the rise in amplitude of the squared envelope of the referenced vibration signals. Thus on one hand, the developed model demonstrated its capability to explain wear behavior and on the other hand it also helps to establish a correlation between wear based and vibration based analysis. Therefore, the model provides a cost-effective and quick approach to predict the impending wear in IC engine bearings under various operating conditions.

Keywords: condition monitoring, IC engine, journal bearings, vibration analysis, wear prediction

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Authors: Bonnie R. Brammall, Rhonda M. Garad, Helena J. Teede, Cheryce L. Harrison

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Introduction: Reproductive aged women are at high-risk for accelerated weight gain and obesity development, with pregnancy recognised as a critical contributory life phase. Healthy lifestyle interventions during the preconception and antenatal period improve maternal and infant health outcomes. Yet, interventions from preconception through to postpartum and translation and implementation into real-world healthcare settings remain limited. OptimalMe is a randomised, hybrid implementation effectiveness study of evidence-based healthy lifestyle intervention. Here, we report engagement, acceptability of the intervention during preconception, and self-reported behaviour change outcomes as a result of the preconception phase of the intervention. Methods: Reproductive aged women who upgraded their private health insurance to include pregnancy and birth cover, signalling a pregnancy intention, were invited to participate. Women received access to an online portal with preconception health and lifestyle modules, goal-setting and behaviour change tools, monthly SMS messages, and two coaching sessions (randomised to video or phone) prior to pregnancy. Results: Overall n=527 expressed interest in participating. Of these, n=33 did not meet inclusion criteria, n=8 were not contactable for eligibility screening, and n=177 failed to engage after the screening, leaving n=309 who were enrolled in OptimalMe and randomised to intervention delivery method. Engagement with coaching sessions dropped by 25% for session two, with no difference between intervention groups. Women had a mean (SD) age of 31.7 (4.3) years and, at baseline, a self-reported mean BMI of 25.7 (6.1) kg/m², with 55.8% (n=172) of a healthy BMI. Behaviour was sub-optimal with infrequent self-weighing (38.1%), alcohol consumption prevalent (57.1%), sub-optimal pre-pregnancy supplementation (61.5%), and incomplete medical screening. Post-intervention 73.2% of women reported engagement with a GP for preconception care and improved lifestyle behaviour (85.5%), since starting OptimalMe. Direct pre-and-post comparison of individual participant data showed that of 322 points of potential change (up-to-date cervical screening, elimination of high-risk behaviours [alcohol, drugs, smoking], uptake of preconception supplements and improved weighing habits) 158 (49.1%) points of change were achieved. Health coaching sessions were found to improve accountability and confidence, yet further personalisation and support were desired. Engagement with video and phone sessions was comparable, having similar impacts on behaviour change, and both methods were well accepted and increased women's accountability. Conclusion: A low-intensity digital health and lifestyle program with embedded health coaching can improve the uptake of preconception care and lead to self-reported behaviour change. This is the first program of its kind to reach an otherwise healthy population of women planning a pregnancy. Women who were otherwise healthy showed divergence from preconception health and lifestyle objectives and benefited from the intervention. OptimalMe shows promising results for population-based behaviour change interventions that can improve preconception lifestyle habits and increase engagement with clinical health care for pregnancy preparation.

Keywords: preconception, pregnancy, preventative health, weight gain prevention, self-management, behaviour change, digital health, telehealth, intervention, women's health

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Authors: S. Thomet, S. De-Paoli, F. Ghaffari, J. M. Daveau, P. Roche, O. Romain

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In this paper, we present a hardware module dedicated to understanding the fail reason of a System on Chip (SoC) exposed to a particle beam. Impact of Single-Event Effects (SEE) on processor-based SoCs is a concern that has increased in the past decade, particularly for terrestrial applications with automotive safety increasing requirements, as well as consumer and industrial domains. The SEE created by the impact of a particle on an SoC may have consequences that can end to instability or crashes. Specific hardening techniques for hardware and software have been developed to make such systems more reliable. SoC is then qualified using cosmic ray Accelerated Soft-Error Rate (ASER) to ensure the Soft-Error Rate (SER) remains in mission profiles. Understanding where errors are occurring is another challenge because of the complexity of operations performed in an SoC. Common techniques to monitor an SoC running under a beam are based on non-intrusive debug, consisting of recording the program counter and doing some consistency checking on the fly. To detect and understand SEE, we have developed a module embedded within the SoC that provide support for recording probes, hardware watchpoints, and a memory mapped register bank dedicated to software usage. To identify CPU failure modes and the most important resources to probe, we have carried out a fault injection campaign on the RTL model of the SoC. Probes are placed on generic CPU registers and bus accesses. They highlight the propagation of errors and allow identifying the failure modes. Typical resulting errors are bit-flips in resources creating bad addresses, illegal instructions, longer than expected loops, or incorrect bus accesses. Although our module is processor agnostic, it has been interfaced to a RISC-V by probing some of the processor registers. Probes are then recorded in a ring buffer. Associated hardware watchpoints are allowing to do some control, such as start or stop event recording or halt the processor. Finally, the module is also providing a bank of registers where the firmware running on the SoC can log information. Typical usage is for operating system context switch recording. The module is connected to a dedicated debug bus and is interfaced to a remote controller via a debugger link. Thus, a remote controller can interact with the monitoring module without any intrusiveness on the SoC. Moreover, in case of CPU unresponsiveness, or system-bus stall, the recorded information can still be recovered, providing the fail reason. A preliminary version of the module has been integrated into a test chip currently being manufactured at ST in 28-nm FDSOI technology. The module has been triplicated to provide reliable information on the SoC behavior. As the primary application domain is automotive and safety, the efficiency of the module will be evaluated by exposing the test chip under a fast-neutron beam by the end of the year. In the meantime, it will be tested with alpha particles and electromagnetic fault injection (EMFI). We will report in the paper on fault-injection results as well as irradiation results.

Keywords: fault injection, SoC fail reason, SoC soft error rate, terrestrial application

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Authors: Supriya Ambawat, Subaran Singh, C. Tara Satyavathi, B. S. Rajpurohit, Ummed Singh, Balraj Singh

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Pearl millet [Pennisetum glaucum (L.) R. Br.] is an important staple food of the arid and semiarid tropical regions of Asia, Africa, and Latin America. It is rightly termed as nutricereal as it has high nutrition value and a good source of carbohydrate, protein, fat, ash, dietary fiber, potassium, magnesium, iron, zinc, etc. Pearl millet has low prolamine fraction and is gluten free which is useful for people having a gluten allergy. It has several health benefits like reduction in blood pressure, thyroid, diabe¬tes, cardiovascular and celiac diseases but its direct consumption as food has significantly declined due to several reasons. Keeping this in view, it is important to reorient the ef¬forts to generate demand through value-addition and quality improvement and create awareness on the nutritional merits of pearl millet. In India, through Indian Council of Agricultural Research-All India Coordinated Research Project on Pearl millet, multilocational coordinated trials for developed hybrids were conducted at various centers. The gene banks of pearl millet contain varieties with high levels of iron and zinc which were used to produce new pearl millet varieties with elevated iron levels bred with the high‐yielding varieties. Thus, using breeding approaches and biochemical analysis, a total of 167 hybrids and 61 varieties were identified and released for cultivation in different agro-ecological zones of the country which also includes some biofortified hybrids rich in Fe and Zn. Further, using several biotechnological interventions such as molecular markers, next-generation sequencing (NGS), association mapping, nested association mapping (NAM), MAGIC populations, genome editing, genotyping by sequencing (GBS), genome wide association studies (GWAS) advancement in millet improvement has become possible by identifying and tagging of genes underlying a trait in the genome. Using DArT markers very high density linkage maps were constructed for pearl millet. Improved HHB67 has been released using marker assisted selection (MAS) strategies, and genomic tools were used to identify Fe-Zn Quantitative Trait Loci (QTL). The draft genome sequence of millet has also opened various ways to explore pearl millet. Further, genomic positions of significantly associated simple sequence repeat (SSR) markers with iron and zinc content in the consensus map is being identified and research is in progress towards mapping QTLs for flour rancidity. The sequence information is being used to explore genes and enzymatic pathways responsible for rancidity of flour. Thus, development and application of several biotechnological approaches along with biofortification can accelerate the genetic gain targets for pearl millet improvement and help improve its quality.

Keywords: Biotechnological approaches, genomic tools, malnutrition, MAS, nutricereal, pearl millet, sequencing.

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Authors: Pule P. Mpopetsi, Warren M. Potts, Nicola James, Amber Childs

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Increased CO₂ production and the consequent ocean acidification (OA) have been identified as one of the greatest threats to both calcifying and non-calcifying marine organisms. Traditionally, marine fishes, as non-calcifying organisms, were considered to have a higher tolerance to near-future OA conditions owing to their well-developed ion regulatory mechanisms. However, recent studies provide evidence to suggest that they may not be as resilient to near-future OA conditions as previously thought. In addition, earlier life stages of marine fishes are thought to be less tolerant than juveniles and adults of the same species as they lack well-developed ion regulatory mechanisms for maintaining homeostasis. This study focused on the effects of near-future OA on larval Argyrosomus japonicus, an estuarine-dependent marine fish species, in order to identify the tipping point of tolerance for the larvae of this species. Larval A. japonicus in the present study were reared from the egg up to 22 days after hatching (DAH) under three treatments. The three treatments, (pCO₂ 353 µatm; pH 8.03), (pCO₂ 451 µatm; pH 7.93) and (pCO₂ 602 µatm; pH 7.83) corresponded to levels predicted to occur in year 2050, 2068 and 2090 respectively under the Intergovernmental Panel on Climate Change (IPCC) Representative Concentration Pathways (IPCC RCP) 8.5 model. Size-at-hatch, growth, development, and metabolic responses (standard and active metabolic rates and metabolic scope) were assessed and compared between the three treatments throughout the rearing period. Five earlier larval life stages (hatchling – flexion/post-flexion) were identified by the end of the experiment. There were no significant differences in size-at-hatch (p > 0.05), development or the active metabolic (p > 0.05) or metabolic scope (p > 0.05) of fish in the three treatments throughout the study. However, the standard metabolic rate was significantly higher in the year 2068 treatment but only at the flexion/post-flexion stage which could be attributed to differences in developmental rates (including the development of the gills) between the 2068 and the other two treatments. Overall, the metabolic scope was narrowest in the 2090 treatment but varied according to life stage. Although not significantly different, metabolic scope in the 2090 treatment was noticeably lower at the flexion stage compared to the other two treatments, and the development appeared slower, suggesting that this could be the stage most prone to OA. The study concluded that, in isolation, OA levels predicted to occur between 2050 and 2090 will not negatively affect size-at-hatch, growth, development, and metabolic responses of larval A. japonicus up to 22 DAH (flexion/post-flexion stage). The present study also identified the tipping point of tolerance (where negative impacts will begin) in larvae of the species to be between the years 2090 and 2100.

Keywords: climate change, ecology, marine, ocean acidification

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Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

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Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

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Authors: Ashish Sinha, Pushpend Agrawal

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Background: Patients with undiagnosed pulmonary TB predominantly act as reservoirs for its transmission through 10-15 secondary infections in the next 1-5 Yrs. Delays in the diagnosis and treatment may worsen the disease with increase the risk of death. Factors responsible for such delays by tracking patient pathways to treatment may help in planning better interventions. The provision of ‘free diagnosis and treatment’ forms the cornerstone of the National Tuberculosis Elimination Programme (NTEP). OOPE is defined as the money spent by the patient during TB care other than public health facilities. Free TB care at all health facilities could reduce out-of-pocket expenses to the minimum possible levels. Material and Methods: This cross-sectional study was conducted among randomly selected 252 TB patients from Nov – Oct 2022 by taking in-depth interviews following informed verbal consent. We documented their journey from initial symptoms until they reached the public health facility, along with their ‘out-of-pocket expenditure’ (OOPE) pertaining to TB care. Results: Total treatment delay was 91±72 days on average (median: 77days, IQR: 45-104 days), while the isolated patient delay was 31±45 days (median: 15 days, IQR: 0 days to 43 days); diagnostic delay; 57±60 days (median: 42days, IQR 14-78 days), treatment delay 19 ± 18 days (median: 15days, IQR: 11-19 days). A patient delay (> 30 days) was significantly associated with ignorance about classic symptoms of pulmonary TB, adoption of self-medication, illiteracy, and middle and lower social class. Diagnostic delay was significantly higher among those who contacted private health facilities, were unaware of signs and symptoms, had >2 consultations, and not getting an appropriate referral for TB care. Most (97%) of the study participants interviewed claimed to have incurred some expenditure.Median total expenses were 6155(IQR: 2625-15175) rupees. More than half 141 (56%) of the study participants had expenses >5000 rupees. Median transport expenses were 525(IQR: 200-1012) rupees; Median consultation expenses were 700(IQR: 200-1600) rupees; Median investigation expenses were 1000(IQR: 0-3025) rupees and the Median medicine expenses were 3350(IQR: 1300-7525).OOPE for consultation, investigation, and medicine was observed to be significantly higher among patients who ignored classical signs& symptoms of TB, repeated visits to private health facilities, and due to self-medication practices. Transport expenses and delays in seeking care at facilities were observed to have an upward trend with OOP Expenses (r =1). Conclusion: Delay in TB care due to low awareness about signs and symptoms of TB and poor seeking care, lack of proper consultation, and appropriate referrals reported by the study subjects indicate the areas which need proper attention by the program managers. Despite a centrally sponsored programme, the financial burden on TB patients is still in the unacceptable range. OOPE could be reduced as low as possible by addressing the responsible factors linked to it.

Keywords: patient pathway, delay, pulmonary tuberculosis, out of pocket expenses

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Authors: Zubair Ahmed, Andrea Barbieri

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The need to reduce energy consumption has prompted a considerable research effort for developing alternative energy-efficient lighting systems to replace conventional light sources (i.e., incandescent and fluorescent lamps). Organic light emitting device (OLED) technology offers the distinctive possibility to fabricate large area flat devices by vacuum or solution processing. Lanthanide β-diketonates complexes, due to unique photophysical properties of Ln(III) ions, have been explored as emitting layers in OLED displays and in solid-state lighting (SSL) in order to achieve high efficiency and color purity. For such applications, the excellent photoluminescence quantum yield (PLQY) and stability are the two key points that can be achieved simply by selecting the proper organic ligands around the Ln ion in a coordination sphere. Regarding the strategies to enhance the PLQY, the most common is the suppression of the radiationless deactivation pathways due to the presence of high-frequency oscillators (e.g., OH, –CH groups) around the Ln centre. Recently, a different approach to maximize the PLQY of Ln(β-DKs) has been proposed (named 'Escalate Coordination Anisotropy', ECA). It is based on the assumption that coordinating the Ln ion with different ligands will break the centrosymmetry of the molecule leading to less forbidden transitions (loosening the constraints of the Laporte rule). The OLEDs based on such complexes are available, but with low efficiency and stability. In order to get efficient devices, there is a need to develop some new Ln complexes with enhanced PLQYs and stabilities. For this purpose, the Ln complexes, both visible and (NIR) emitting, of variant coordination structures based on the various fluorinated/non-fluorinated β-diketones and O/N-donor neutral ligands were synthesized using a one step in situ method. In this method, the β-diketones, base, LnCl₃.nH₂O and neutral ligands were mixed in a 3:3:1:1 M ratio in ethanol that gave air and moisture stable complexes. Further, they were characterized by means of elemental analysis, NMR spectroscopy and single crystal X-ray diffraction. Thereafter, their photophysical properties were studied to select the best complexes for the fabrication of stable and efficient OLEDs. Finally, the OLEDs were fabricated and investigated using these complexes as emitting layers along with other organic layers like NPB,N,N′-Di(1-naphthyl)-N,N′-diphenyl-(1,1′-biphenyl)-4,4′-diamine (hole-transporting layer), BCP, 2,9-Dimethyl-4,7-diphenyl-1,10-phenanthroline (hole-blocker) and Alq3 (electron-transporting layer). The layers were sequentially deposited under high vacuum environment by thermal evaporation onto ITO glass substrates. Moreover, co-deposition techniques were used to improve charge transport in the devices and to avoid quenching phenomena. The devices show strong electroluminescence at 612, 998, 1064 and 1534 nm corresponding to ⁵D₀ →⁷F₂(Eu), ²F₅/₂ → ²F₇/₂ (Yb), ⁴F₃/₂→ ⁴I₉/₂ (Nd) and ⁴I1₃/₂→ ⁴I1₅/₂ (Er). All the devices fabricated show good efficiency as well as stability.

Keywords: electroluminescence, lanthanides, paramagnetic NMR, photoluminescence

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Authors: Shang Yee Chong

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Perioperative pain is a complex mechanism activated by various nociceptive, neuropathic, and inflammatory pathways. Opioids have long been a mainstay for analgesia in this period, even as we are continuously moving towards a multimodal model to improve pain control while minimising side effects. Dexmedetomidine, a potent alpha-2 agonist, is a useful sedative and hypnotic agent. Its use in the intensive care unit has been well described, and it is increasingly an adjunct intraoperatively for its opioid sparing effects and to decrease pain scores. We describe a case of a general surgical patient in whom minimal opioids was required with dexmedetomidine use. The patient was a 61-year-old Indian gentleman with a history of hyperlipidaemia and type 2 diabetes mellitus, presenting with rectal adenocarcinoma detected on colonoscopy. He was scheduled for a robotic ultra-low anterior resection. The patient was induced with intravenous fentanyl 75mcg, propofol 160mg and atracurium 40mg. He was intubated conventionally and mechanically ventilated. Anaesthesia was maintained with inhalational desflurane and anaesthetic depth was measured with the Masimo EEG Sedline brain function monitor. An initial intravenous dexmedetomidine dose (bolus) of 1ug/kg for 10 minutes was given prior to anaesthetic induction and thereafter, an infusion of 0.2-0.4ug/kg/hr to the end of surgery. In addition, a bolus dose of intravenous lignocaine 1.5mg/kg followed by an infusion at 1mg/kg/hr throughout the surgery was administered. A total of 10mmol of magnesium sulphate and intravenous paracetamol 1000mg were also given for analgesia. There were no significant episodes of bradycardia or hypotension. A total of intravenous phenylephrine 650mcg was given throughout to maintain the patient’s mean arterial pressure within 10-15mmHg of baseline. The surgical time lasted for 5 hours and 40minutes. Postoperatively the patient was reversed and extubated successfully. He was alert and comfortable and pain scores were minimal in the immediate post op period in the postoperative recovery unit. Time to first analgesia was 4 hours postoperatively – with paracetamol 1g administered. This was given at 6 hourly intervals strictly for 5 days post surgery, along with celecoxib 200mg BD as prescribed by the surgeon regardless of pain scores. Oral oxycodone was prescribed as a rescue analgesic for pain scores > 3/10, but the patient did not require any dose. Neither was there nausea or vomiting. The patient was discharged on postoperative day 5. This case has reinforced the use of dexmedetomidine as an adjunct in general surgery cases, highlighting its excellent opioid-sparing effects. In the entire patient’s hospital stay, the only dose of opioid he received was 75mcg of fentanyl at the time of anaesthetic induction. The patient suffered no opioid adverse effects such as nausea, vomiting or postoperative ileus, and pain scores varied from 0-2/10. However, intravenous lignocaine infusion was also used in this instance, which would have helped improve pain scores. Paracetamol, lignocaine, and dexmedetomidine is thus an effective, opioid-sparing combination of multi-modal analgesia for major abdominal surgery cases.

Keywords: analgesia, dexmedetomidine, general surgery, opioid sparing

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Authors: B. Philip, J. Littlewood, R. Radford, N. Evans, T. Whyman, D. P. Jones

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UK buildings and energy infrastructures are heavily dependent on natural gas, a large proportion of which is used for domestic space heating. However, approximately half of the gas consumed in the UK is imported. Improving energy security and reducing carbon emissions are major government drivers for reducing gas dependency. In order to do so there needs to be a wholesale shift in the energy provision to householders without impacting on thermal comfort levels, convenience or cost of supply to the end user. Heat pumps are seen as a potential alternative in modern well insulated homes, however, can the same be said of older homes? A large proportion of housing stock in Britain was built prior to 1919. The age of the buildings bears testimony to the quality of construction; however, their thermal performance falls far below the minimum currently set by UK building standards. In recent years significant sums of money have been invested to improve energy efficiency and combat fuel poverty in some of the most deprived areas of Wales. Increasing energy efficiency of older properties remains a significant challenge, which cannot be achieved through insulation and air-tightness interventions alone, particularly when alterations to historically important architectural features of the building are not permitted. This paper investigates the energy demand of pre-1919 dwellings in a former Welsh mining village, the feasibility of meeting that demand using water from the disused mine workings to supply a district heat network and potential barriers to success of the scheme. The use of renewable solar energy generation and storage technologies, both thermal and electrical, to reduce the load and offset increased electricity demand, are considered. A wholistic surveying approach to provide a more accurate assessment of total household heat demand is proposed. Several surveying techniques, including condition surveys, air permeability, heat loss calculations, and thermography were employed to provide a clear picture of energy demand. Additional insulation can bring unforeseen consequences which are detrimental to the fabric of the building, potentially leading to accelerated dilapidation of the asset being ‘protected’. Increasing ventilation should be considered in parallel, to compensate for the associated reduction in uncontrolled infiltration. The effectiveness of thermal performance improvements are demonstrated and the detrimental effects of incorrect material choice and poor installation are highlighted. The findings show estimated heat demand to be in close correlation to household energy bills. Major areas of heat loss were identified such that improvements to building thermal performance could be targeted. The findings demonstrate that the use of heat pumps in older buildings is viable, provided sufficient improvement to thermal performance is possible. Addition of passive solar thermal and photovoltaic generation can help reduce the load and running cost for the householder. The results were used to predict future heat demand following energy efficiency improvements, thereby informing the size of heat pumps required.

Keywords: heat demand, heat pump, renewable energy, retrofit

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Authors: Tarek Saadawi, Rosario Gennaro, Jonathan Akeley

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There is rapidly growing demand for professionals to fill positions in Cybersecurity. This is recognized as a national priority both by government agencies and the private sector. Cybersecurity is a very wide technical area which encompasses all measures that can be taken in an electronic system to prevent criminal or unauthorized use of data and resources. This requires defending computers, servers, networks, and their users from any kind of malicious attacks. The need to address this challenge has been recognized globally but is particularly acute in the New York metropolitan area, home to some of the largest financial institutions in the world, which are prime targets of cyberattacks. In New York State alone, there are currently around 57,000 jobs in the Cybersecurity industry, with more than 23,000 unfilled positions. The Cybersecurity Program at City College is a collaboration between the Departments of Computer Science and Electrical Engineering. In Fall 2020, The City College of New York matriculated its first students in theCybersecurity Master of Science program. The program was designed to fill gaps in the previous offerings and evolved out ofan established partnership with Facebook on Cybersecurity Education. City College has designed a program where courses, curricula, syllabi, materials, labs, etc., are developed in cooperation and coordination with industry whenever possible, ensuring that students graduating from the program will have the necessary background to seamlessly segue into industry jobs. The Cybersecurity Program has created multiple pathways for prospective students to obtain the necessary prerequisites to apply in order to build a more diverse student population. The program can also be pursued on a part-time basis which makes it available to working professionals. Since City College’s Cybersecurity M.S. program was established to equip students with the advanced technical skills needed to thrive in a high-demand, rapidly-evolving field, it incorporates a range of pedagogical formats. From its outset, the Cybersecurity program has sought to provide both the theoretical foundations necessary for meaningful work in the field along with labs and applied learning projects aligned with skillsets required by industry. The efforts have involved collaboration with outside organizations and with visiting professors designing new courses on topics such as Adversarial AI, Data Privacy, Secure Cloud Computing, and blockchain. Although the program was initially designed with a single asynchronous course in the curriculum with the rest of the classes designed to be offered in-person, the advent of the COVID-19 pandemic necessitated a move to fullyonline learning. The shift to online learning has provided lessons for future development by providing examples of some inherent advantages to the medium in addition to its drawbacks. This talk will address the structure of the newly-implemented Cybersecurity Master’s Program and discuss the innovations, challenges, and possible future directions.

Keywords: cybersecurity, new york, city college, graduate degree, master of science

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Authors: W. S. Barber, S. L. King

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This paper reports on a pilot project to develop a collaborative partnership between a community college in rural northern Ontario, Canada, and an urban university in the greater Toronto area in Oshawa, Canada. Partner institutions will collaborate to address learning needs of university applicants whose goals are to attain an undergraduate university BA in Educational Studies and Digital Technology degree, but who may not live in a geographical location that would facilitate this pathways process. The UOIT BA degree is attained through a 2+2 program, where students with a 2 year college diploma or equivalent can attain a four year undergraduate degree. The goals reported on the project are as: 1. Our aim is to expand the BA program to include an additional stream which includes serious educational games, simulations and virtual environments, 2. Develop fully (using both synchronous and asynchronous technologies) online learning modules for use by university applicants who otherwise are not geographically located close to a physical university site, 3. Assess the digital competencies of all students, including members of local, distance and Indigenous communities using a validated tool developed and tested by UOIT across numerous populations. This tool, the General Technical Competency Use and Scale (GTCU) will provide the collaborating institutions with data that will allow for analyzing how well students are prepared to succeed in fully online learning communities. Philosophically, the UOIT BA program is based on a fully online learning communities model (FOLC) that can be accessed from anywhere in the world through digital learning environments via audio video conferencing tools such as Adobe Connect. It also follows models of adult learning and mobile learning, and makes a university degree accessible to the increasing demographic of adult learners who may use mobile devices to learn anywhere anytime. The program is based on key principles of Problem Based Learning, allowing students to build their own understandings through the co-design of the learning environment in collaboration with the instructors and their peers. In this way, this degree allows students to personalize and individualize the learning based on their own culture, background and professional/personal experiences. Using modified flipped classroom strategies, students are able to interrogate video modules on their own time in preparation for one hour discussions occurring in video conferencing sessions. As a consequence of the program flexibility, students may continue to work full or part time. All of the partner institutions will co-develop four new modules, administer the GTCU and share data, while creating a new stream of the UOIT BA degree. This will increase accessibility for students to bridge from community colleges to university through a fully digital environment. We aim to work collaboratively with Indigenous elders, community members and distance education instructors to increase opportunities for more students to attain a university education.

Keywords: aboriginal, college, competencies, digital, universities

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Authors: Elias Jemal Abdella

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The Blue Nile River is an important shared resource of Ethiopia, Sudan and also, because it is the major contributor of water to the main Nile River, Egypt. Despite the potential benefits of regional cooperation and integrated joint basin management, all three countries continue to pursue unilateral plans for development. Besides, there is great uncertainty about the likely impacts of climate change in water availability for existing as well as proposed irrigation and hydropower projects in the Blue Nile Basin. The main objective of this study is to quantitatively assess the impact of climate change on the hydrological regime of the upper Blue Nile basin, western Ethiopia. Three models were combined, a dynamic Coordinated Regional Climate Downscaling Experiment (CORDEX) regional climate model (RCM) that is used to determine climate projections for the Upper Blue Nile basin for Representative Concentration Pathways (RCPs) 4.5 and 8.5 greenhouse gas emissions scenarios for the period 2021-2050. The outputs generated from multimodel ensemble of four (4) CORDEX-RCMs (i.e., rainfall and temperature) were used as input to a Soil and Water Assessment Tool (SWAT) hydrological model which was setup, calibrated and validated with observed climate and hydrological data. The outputs from the SWAT model (i.e., projections in river flow) were used as input to a Water Evaluation and Planning (WEAP) water resources model which was used to determine the water resources implications of the changes in climate. The WEAP model was set-up to simulate three development scenarios. Current Development scenario was the existing water resource development situation, Medium-term Development scenario was planned water resource development that is expected to be commissioned (i.e. before 2025) and Long-term full Development scenario were all planned water resource development likely to be commissioned (i.e. before 2050). The projected change of mean annual temperature for period (2021 – 2050) in most of the basin are warmer than the baseline (1982 -2005) average in the range of 1 to 1.4oC, implying that an increase in evapotranspiration loss. Subbasins which already distressed from drought may endure to face even greater challenges in the future. Projected mean annual precipitation varies from subbasin to subbasin; in the Eastern, North Eastern and South western highland of the basin a likely increase of mean annual precipitation up to 7% whereas in the western lowland part of the basin mean annual precipitation projected to decrease by 3%. The water use simulation indicates that currently irrigation demand in the basin is 1.29 Bm3y-1 for 122,765 ha of irrigation area. By 2025, with new schemes being developed, irrigation demand is estimated to increase to 2.5 Bm3y-1 for 277,779 ha. By 2050, irrigation demand in the basin is estimated to increase to 3.4 Bm3y-1 for 372,779 ha. The hydropower generation simulation indicates that 98 % of hydroelectricity potential could be produced if all planned dams are constructed.

Keywords: Blue Nile River, climate change, hydropower, SWAT, WEAP

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Authors: Amirah Azzeri, Fatiha H. Shabaruddin, Scott A. McDonald, Rosmawati Mohamed, Maznah Dahlui

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Objective: A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to Sofosbuvir/Daclatasvir (SOF/DAC) is available through compulsory licensing, with future access to Sofosbuvir/Velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes, particularly for cirrhotic stages, but has higher drug acquisition costs compared to SOF/DAC. It has been proposed that a stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a five-year budget impact analysis from the provider perspective of the proposed stratified treatment cascade for HCV treatment in Malaysia. Method: A disease progression model that was developed based on model-predicted HCV epidemiology data in Malaysia was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. The model projections estimated the annual numbers of patients in care and the numbers of patients to be initiated on DAA treatment nationally. Healthcare costs associated with DAA therapy and disease stage monitoring was included to estimate the downstream cost implications. For scenario B, the estimated treatment uptake of SOF/VEL for cirrhotic patients were 25%, 50%, 75%, 100% and 100% for 2018, 2019, 2020, 2021 and 2022 respectively. Healthcare costs were estimated based on standard clinical pathways for DAA treatment described in recent guidelines. All costs were reported in US dollars (conversion rate US$1=RM4.09, the price year 2018). Scenario analysis was conducted for 5% and 10% reduction of SOF/VEL acquisition cost anticipated from the competitive market pricing of generic DAA in Malaysia. Results: The stratified treatment cascade with SOF/VEL in Scenario B was found to be cost-saving compared to Scenario A. A substantial portion of the cost reduction was due to the costs associated with DAA therapy which resulted in USD 40 thousand (year 1) to USD 443 thousand (year 5) savings annually, with cumulative savings of USD 1.1 million after 5 years. Cost reductions for disease stage monitoring were seen in year three onwards which resulted in cumulative savings of USD 1.1 thousand. Scenario analysis estimated cumulative savings of USD 1.24 to USD 1.35 million when the acquisition cost of SOF/VEL was reduced. Conclusion: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can results in a budget impact reduction in overall healthcare expenditure in Malaysia compared to treatment with SOF/DAC. The better clinical efficacy with SOF/VEL is expected to halt patients’ HCV disease progression and may reduce downstream costs of treating advanced disease stages. The findings of this analysis may be useful to inform healthcare policies for HCV treatment in Malaysia.

Keywords: Malaysia, direct acting antiviral, compulsory licensing, voluntary licensing

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Authors: Rose Branch-Allen, John Jayachandran

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Background and purpose: Canada is a pluralistic, multicultural society with an ethno-cultural composition that has been shaped over time by immigrants and their descendants. Although Canada welcomes these immigrants, many will endure hardship and assimilation difficulties. Despite these life hurdles, surveys consistently disclose high life satisfaction for all Canadians. Most research studies on Life Satisfaction/ Subjective Wellbeing (SWB) have focused on one main determinant and a variety of social demographic variables to delineate the determinants of life satisfaction. However, very few research studies examine life satisfaction from a holistic approach. In addition, we need to understand the causal pathways leading to life satisfaction, and develop theories that explain why certain variables differentially influence the different components of SWB. The aim this study was to utilize a holistic approach to construct a causal model and identify major determinants of life satisfaction. Data and measures: This study utilized data from the General Social Survey, with a sample size of 19, 597. The exogenous concepts included age, gender, marital status, household size, socioeconomic status, ethnicity, location, immigration status, religiosity, and neighborhood. The intervening concepts included health, social contact, leisure, enjoyment, work-family balance, quality time, domestic labor, and sense of belonging. The endogenous concept life satisfaction was measured by multiple indicators (Cronbach’s alpha = .83). Analysis: Several multiple regression models were run sequentially to estimate path coefficients for the causal model. Results: Overall, above average satisfaction with life was reported for respondents with specific socio-economic, demographic and lifestyle characteristics. With regard to exogenous factors, respondents who were female, younger, married, from high socioeconomic status background, born in Canada, very religious, and demonstrated high level of neighborhood interaction had greater satisfaction with life. Similarly, intervening concepts suggested respondents had greater life satisfaction if they had better health, more social contact, less time on passive leisure activities and more time on active leisure activities, more time with family and friends, more enjoyment with volunteer activities, less time on domestic labor and a greater sense of belonging to the community. Conclusions and Implications: Our results suggest that a holistic approach is necessary for establishing determinants of life satisfaction, and that life satisfaction is not merely comprised of positive or negative affect rather understanding the causal process of life satisfaction. Even though, most of our findings are consistent with previous studies, a significant number of causal connections contradict some of the findings in literature today. We have provided possible explanation for these anomalies researchers encounter in studying life satisfaction and policy implications.

Keywords: causal model, holistic approach, life satisfaction, socio-demographic variables, subjective well-being

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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Authors: Kelly Jaunzems

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Social media is a powerful instrument of communication, enabling the presentation of information in multiple forms and modes, amplifying the interactions between people, organisations, and stakeholders, and increasing the range of communication channels available. Younger generations are highly engaged with social media and more likely to use this channel than any other to seek information. Given this, it may appear extraordinary that occupational safety and health professionals have yet to seriously engage with social media for communicating safety messages to younger audiences who, in many industries, might be statistically more likely to encounter more workplace harm or injury. Millennials, defined as those born between 1981-2000, have distinctive characteristics that also impact their interaction patterns rendering many traditional occupational safety and health communication channels sub-optimal or near obsolete. Used to immediate responses, 280-character communication, shares, likes, and visual imagery, millennials struggle to take seriously the low-tech, top-down communication channels such as safety noticeboards, toolbox meetings, and passive tick-box online inductions favoured by traditional OSH professionals. This paper draws upon well-established communication findings, which argue that it is important to know a target audience and reach them using their preferred communication pathways, particularly if the aim is to impact attitudes and behaviours. Health practitioners have adopted social media as a communication channel with great success, yet safety practitioners have failed to follow this lead. Using a digital ethnography approach, this paper examines seven organisations’ Facebook posts from two one-month periods one year apart, one in 2018 and one in 2019. Each of the years informs organisation-based case studies. Comparing, contrasting, and drawing upon these case studies, the paper discusses and evaluates the (non) use of social media communication of safety information in terms of user engagement, shareability, and overall appeal. The success of health practitioners’ use of social media provides a compelling template for the implementation of social media into organisations’ safety communication strategies. Highly visible content such as that found on social media allows an organization to become more responsive and engage in two-way conversations with their audience, creating more engaged and participatory conversations around safety. Further, using social media to address younger audiences with a range of tonal qualities (for example, the use of humour) can achieve cut through in a way that grim statistics fail to do. On the basis of 18 months of interviews, filed work, and data analysis, the paper concludes with recommendations for communicating safety information via social media. It proposes exploration of the social media communication formula that, when utilised by safety practitioners, may create an effective social media presence. It is anticipated that such social media use will increase engagement, expand the number of followers and reduce the likelihood and severity of safety-related incidents. The tools offered may provide a path for safety practitioners to reach a disengaged generation of workers to build a cohesive and inclusive conversation around ways to keep people safe at work.

Keywords: social media, workplace safety, communication strategies, young workers

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

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Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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Authors: Islam Sherif, Ahmed Ashour, Ahmed Hassan, Hatem Osman

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Anterior Cruciate Ligament (ACL) injuries are common among athletes and individuals participating in sports with sudden stops, pivots, and changes in direction. Arthroscopic surgery is the gold standard for ACL reconstruction, aiming to restore knee stability and function. Recent years have witnessed significant advancements in arthroscopic surgery techniques, graft materials, and technological innovations, revolutionizing the field of ACL reconstruction. This presentation delves into the latest advancements in arthroscopic surgery techniques for ACL reconstruction and their potential impact on patient outcomes. Traditionally, autografts from the patellar tendon, hamstring tendon, or quadriceps tendon have been commonly used for ACL reconstruction. However, recent studies have explored the use of allografts, synthetic scaffolds, and tissue-engineered grafts as viable alternatives. This abstract evaluates the benefits and potential drawbacks of each graft type, considering factors such as graft incorporation, strength, and risk of graft failure. Moreover, the application of augmented reality (AR) and virtual reality (VR) technologies in surgical planning and intraoperative navigation has gained traction. AR and VR platforms provide surgeons with detailed 3D anatomical reconstructions of the knee joint, enhancing preoperative visualization and aiding in graft tunnel placement during surgery. We discuss the integration of AR and VR in arthroscopic ACL reconstruction procedures, evaluating their accuracy, cost-effectiveness, and overall impact on surgical outcomes. Beyond graft selection and surgical navigation, patient-specific planning has gained attention in recent research. Advanced imaging techniques, such as MRI-based personalized planning, enable surgeons to tailor ACL reconstruction procedures to each patient's unique anatomy. By accounting for individual variations in the femoral and tibial insertion sites, this personalized approach aims to optimize graft placement and potentially improve postoperative knee kinematics and stability. Furthermore, rehabilitation and postoperative care play a crucial role in the success of ACL reconstruction. This abstract explores novel rehabilitation protocols, emphasizing early mobilization, neuromuscular training, and accelerated recovery strategies. Integrating technology, such as wearable sensors and mobile applications, into postoperative care can facilitate remote monitoring and timely intervention, contributing to enhanced rehabilitation outcomes. In conclusion, this presentation provides an overview of the cutting-edge advancements in arthroscopic surgery techniques for ACL reconstruction. By embracing innovative graft materials, augmented reality, patient-specific planning, and technology-driven rehabilitation, orthopedic surgeons and sports medicine specialists can achieve superior outcomes in ACL injury management. These developments hold great promise for improving the functional outcomes and long-term success rates of ACL reconstruction, benefitting athletes and patients alike.

Keywords: arthroscopic surgery, ACL, autograft, allograft, graft materials, ACL reconstruction, synthetic scaffolds, tissue-engineered graft, virtual reality, augmented reality, surgical planning, intra-operative navigation

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Authors: Casta Guillaume, Robert Jagers, Deborah Rivas-Drake

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Civically engaged youth are critical to maintaining and/or improving the functioning of local, national and global communities and their institutions. The present study investigated how school climate and academic beliefs (academic self-efficacy and school belonging) may inform emergent civic behaviors (emergent citizenship) among self-identified middle school youth of color (African American, Multiracial or Mixed, Latino, Asian American or Pacific Islander, Native American, and other). Study aims: 1) Understand whether and how school climate is associated with civic engagement behaviors, directly and indirectly, by fostering a positive sense of connection to the school and/or engendering feelings of self-efficacy in the academic domain. Accordingly, we examined 2) The association of youths’ sense of school connection and academic self-efficacy with their personally responsible and participatory civic behaviors in school and community contexts—both concurrently and longitudinally. Data from two subsamples of a larger study of social/emotional development among middle school students were used for longitudinal and cross sectional analysis. The cross-sectional sample included 324 6th-8th grade students, of which 43% identified as African American, 20% identified as Multiracial or Mixed, 18% identified as Latino, 12% identified as Asian American or Pacific Islander, 6% identified as Other, and 1% identified as Native American. The age of the sample ranged from 11 – 15 (M = 12.33, SD = .97). For the longitudinal test of our mediation model, we drew on data from the 6th and 7th grade cohorts only (n =232); the ethnic and racial diversity of this longitudinal subsample was virtually identical to that of the cross-sectional sample. For both the cross-sectional and longitudinal analyses, full information maximum likelihood was used to deal with missing data. Fit indices were inspected to determine if they met the recommended thresholds of RMSEA below .05 and CFI and TLI values of at least .90. To determine if particular mediation pathways were significant, the bias-corrected bootstrap confidence intervals for each indirect pathway were inspected. Fit indices for the latent variable mediation model using the cross-sectional data suggest that the hypothesized model fit the observed data well (CFI = .93; TLI =. 92; RMSEA = .05, 90% CI = [.04, .06]). In the model, students’ perceptions of school climate were significantly and positively associated with greater feelings of school connectedness, which were in turn significantly and positively associated with civic engagement. In addition, school climate was significantly and positively associated with greater academic self-efficacy, but academic self-efficacy was not significantly associated with civic engagement. Tests of mediation indicated there was one significant indirect pathway between school climate and civic engagement behavior. There was an indirect association between school climate and civic engagement via its association with sense of school connectedness, indirect association estimate = .17 [95% CI: .08, .32]. The aforementioned indirect association via school connectedness accounted for 50% (.17/.34) of the total effect. Partial support was found for the prediction that students’ perceptions of a positive school climate are linked to civic engagement in part through their role in students’ sense of connection to school.

Keywords: civic engagement, early adolescence, school climate, school belonging, developmental niche

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Authors: Nicole Selvi Hill, Archchana Radhakrishnan

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Introduction: Traumatic brain injury (TBI) is a leading cause of mortality among trauma patients. In the management of TBI, the main principle is avoiding cerebral ischemia, as this is a strong determiner of neurological outcomes. The use of vasoactive drugs, such as vasopressin, has an important role in maintaining cerebral perfusion pressure to prevent secondary brain injury. Current guidelines do not suggest a preferred vasoactive drug to administer in the management of TBI, and there is a paucity of information on the therapeutic potential of vasopressin following TBI. Vasopressin is also an endogenous anti-diuretic hormone (AVP), and pathways mediated by AVP play a large role in the underlying pathological processes of TBI. This creates an overlap of discussion regarding the therapeutic potential of vasopressin following TBI. Currently, its popularity lies in vasodilatory and cardiogenic shock in the intensive care setting, with increasing support for its use in haemorrhagic and septic shock. Methodology: This is a review article based on a literature review. An electronic search was conducted via PubMed, Cochrane, EMBASE, and Google Scholar. The aim was to identify clinical studies looking at the therapeutic administration of vasopressin in severe traumatic brain injury. The primary aim was to look at the neurological outcome of patients. The secondary aim was to look at surrogate markers of cerebral perfusion measurements, such as cerebral perfusion pressure, cerebral oxygenation, and cerebral blood flow. Results: Eight papers were included in the final number. Three were animal studies; five were human studies, comprised of three case reports, one retrospective review of data, and one randomised control trial. All animal studies demonstrated the benefits of vasopressors in TBI management. One animal study showed the superiority of vasopressin in reducing intracranial pressure and increasing cerebral oxygenation over a catecholaminergic vasopressor, phenylephrine. All three human case reports were supportive of vasopressin as a rescue therapy in catecholaminergic-resistant hypotension. The retrospective review found vasopressin did not increase cerebral oedema in TBI patients compared to catecholaminergic vasopressors; and demonstrated a significant reduction in the requirements of hyperosmolar therapy in patients that received vasopressin. The randomised control trial results showed no significant differences in primary and secondary outcomes between TBI patients receiving vasopressin versus those receiving catecholaminergic vasopressors. Apart from the randomised control trial, the studies included are of low-level evidence. Conclusion: Studies favour vasopressin within certain parameters of cerebral function compared to control groups. However, the neurological outcomes of patient groups are not known, and animal study results are difficult to extrapolate to humans. It cannot be said with certainty whether vasopressin’s benefits stand above usage of other vasoactive drugs due to the weaknesses of the evidence. Further randomised control trials, which are larger, standardised, and rigorous, are required to improve knowledge in this field.

Keywords: catecholamines, cerebral perfusion pressure, traumatic brain injury, vasopressin, vasopressors

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Authors: Mara Aparecida De Castilho Lopes. Maria Eliza Mattosinho Bernardes

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The education of deaf individuals in Brazil is grounded in the bilingual approach, which presupposes Brazilian Sign Language (Libras) as the first language for these students. In this perspective, Portuguese should be taught as a second language in its written form, ensuring that deaf students also have access to various academic subjects in sign language. Brazilian legislation (Federal Decree No. 5626 of 2005) mandates the teaching of Brazilian Sign Language in university teacher training programs, but there is no pre-established minimum workload. As a result, there is a significant disparity in the teaching and quality of teacher education across the Brazilian territory. Added to this fact is the general lack of awareness within society regarding the linguistic status of Libras, leading to a shortage of competent teachers for its use and instruction, particularly in higher education. Recently, Federal Law No. 14191 of 2021 established bilingual education for the deaf as a mode of instruction, indicating the need for adjustments in teacher training within higher education teacher preparation programs. Given this context, the objective of the present study was to analyze the teaching proposals for Brazilian Sign Language for students in teacher training programs at public universities in Brazil, presenting alternatives to overcome the current models and academic pathways of teaching and learning. In addition to analyzing Brazilian teaching models, an analysis of a continuing education model for teachers in a French institution was also conducted - considering the historical Franco-Brazilian path of deaf education in Brazil. The analysis of the current teacher training model for deaf education in Brazil revealed that initial exposure to sign language and its linguistic structure is not sufficient to provide future teachers with opportunities to reflect on bilingual teaching methods and practices, as seen in other definitions of bilingualism - bilingual education for proficient listeners in two oral languages. As a result, a training proposal was developed for an experimental interdisciplinary course, integrating the curriculum of an initial and continuing teacher training program alongside the Alfredo Bossi Chair at the University of São Paulo. This proposal is structured into three disciplines, which constitute consecutive moments in teacher education: Fundamental Aspects of Brazilian Sign Language, Bilingual Teaching Methodology, and Teaching Investigation Project - interdisciplinary engagement in the field of deafness. The last offered discipline represents an interdisciplinary supervised internship proposal, considering the multi-professional context that constitutes deaf education within a bilingual approach. In interdisciplinary work within the field of deafness, dialogue between teachers and other professionals who work with deaf students from different perspectives - teachers, speech therapists, and sign language interpreters - is frequently necessary. Through alternative avenues, these actions aim to direct the linguistic development of deaf students within their learning processes. Based on the innovative curriculum proposal described here, the intention is to contribute to the enhancement of teacher education in Brazil, with the goal of ensuring bilingual education for deaf students.

Keywords: bilingual education, teacher training, historical-cultural approach, interdisciplinary education, inclusive education

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Authors: Andrés Quiroz, Emilio Hormazabal, Ana Mutis, Fernando Ortega, Manuel Chacón-Fuentes, Leonardo Parra

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Red clover (Trifolium pratense L.) is an important forage species in temperate regions of the world. The main limitation of this species worldwide is a lack of persistence related to the high mortality of plants due to a complex of biotic and abiotic factors, determining a life span of two or three seasons. Because of the importance of red clover in Chile, a red clover breeding program was started at INIA Carillanca Research Center in 1989, with the main objective of improving the survival of plants, forage yield, and persistence. The main selection criteria for selecting new varieties have been based on agronomical parameters and biotic factors. The main biotic factor associated with red clover mortality in Chile is Hylastinus obscurus (Coleoptera: Curculionidae). Both larval and adults feed on the roots, causing weakening and subsequent death of clover plants. Pesticides have not been successful for controlling infestations of this root borer. Therefore, alternative strategies for controlling this pest are a high priority for red clover producers. Currently, the role of semiochemical in the interaction between H. obscurus and red clover plants has been widely studied for our group. Specifically, from the red clover foliage has been identified limonene is eliciting repellency from the root borer. Limonene is generated in the plant from two independent biosynthetic pathways, the mevalonic acid, and deoxyxylulose pathway. Mevalonate pathway enzymes are localized in the cytosol, whereas the deoxyxylulose phosphate pathway enzymes are found in plastids. In summary, limonene can be determinated by enzymatic bioassay using GPP as substrate and by limonene synthase expression. Therefore, the main objective of this work was to study genetic variation of limonene in material provided by INIA´s Red Clover breeding program. Protein extraction was carried out homogenizing 250 mg of leave tissue and suspended in 6 mL of extraction buffer (PEG 1500, PVP-30, 20 mM MgCl2 and antioxidants) and stirred on ice for 20 min. After centrifugation, aliquots of 2.5 mL were desalted on PD-10 columns, resulting in a final volume of 3.5 mL. Protein determination was performed according to Bradford with BSA as a standard. Monoterpene synthase assays were performed with 50 µL of protein extracts transferred into gas-tight 2 mL crimp seal vials after addition of 4 µL MgCl₂ and 41 µL assay buffer. The assay was started by adding 5 µL of a GPP solution. The mixture was incubated for 30 min at 40 °C. Biosynthesized limonene was quantified in a GC equipped with a chiral column and using synthetic R and S-limonene standards. The enzymatic the production of R and S-limonene from different Superqueli-Carillanca genotypes is shown in this work. Preliminary results showed significant differences in limonene content among the genotypes analyzed. These results constitute an important base for selecting genotypes with a high content of this repellent monoterpene towards H. obscurus.

Keywords: head space, limonene enzymatic determination, red clover, Hylastinus obscurus

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Authors: Fernanda Bravo Cornejo, Camilo Cerda Sarabia, Belén Díaz Díaz, Diego Santibañez Oyarce, Esteban Gómez Terán, Hugo Osses Prado, Raúl Caulier-Cisterna, Jorge Vergara-Quezada, Ana Moya-Beltrán

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Streptococcus pyogenes is a gram-positive bacteria involved in a wide range of diseases and is a major-human-specific bacterial pathogen. In Chile, this year the 'Ministerio de Salud' declared an alert due to the increase in strains throughout the year. This increase can be attributed to the multitude of factors including antimicrobial resistance (AMR) and Virulence Factors (VF). Understanding these VF and AMR is crucial for developing effective strategies and improving public health responses. Moreover, experimental identification and characterization of these pathogenic mechanisms are labor-intensive and time-consuming. Therefore, new computational methods are required to provide robust techniques for accelerating this identification. Advances in Machine Learning (ML) algorithms represent the opportunity to refine and accelerate the discovery of VF associated with Streptococcus pyogenes. In this work, we evaluate the accuracy of various machine learning models in predicting the virulence factors and antimicrobial resistance of Streptococcus pyogenes, with the objective of providing new methods for identifying the pathogenic mechanisms of this organism.Our comprehensive approach involved the download of 32,798 genbank files of S. pyogenes from NCBI dataset, coupled with the incorporation of data from Virulence Factor Database (VFDB) and Antibiotic Resistance Database (CARD) which contains sequences of AMR gene sequence and resistance profiles. These datasets provided labeled examples of both virulent and non-virulent genes, enabling a robust foundation for feature extraction and model training. We employed preprocessing, characterization and feature extraction techniques on primary nucleotide/amino acid sequences and selected the optimal more for model training. The feature set was constructed using sequence-based descriptors (e.g., k-mers and One-hot encoding), and functional annotations based on database prediction. The ML models compared are logistic regression, decision trees, support vector machines, neural networks among others. The results of this work show some differences in accuracy between the algorithms, these differences allow us to identify different aspects that represent unique opportunities for a more precise and efficient characterization and identification of VF and AMR. This comparative analysis underscores the value of integrating machine learning techniques in predicting S. pyogenes virulence and AMR, offering potential pathways for more effective diagnostic and therapeutic strategies. Future work will focus on incorporating additional omics data, such as transcriptomics, and exploring advanced deep learning models to further enhance predictive capabilities.

Keywords: antibiotic resistance, streptococcus pyogenes, virulence factors., machine learning

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Authors: Z. Zaman Asam, M. Ajmal, R. Saeed, H. Miraj, M. Muhammad Ahtisham, B. Hameed, A. -Sattar Nizami

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In Pakistan, environmental degradation and consequent human health deterioration has rapidly accelerated in the past decade due to solid waste mismanagement. As the situation worsens with time, establishment of proper waste management practices is urgently needed especially in semi urban and rural areas of Pakistan. This study uses a concept of Waste Bank, which involves a transfer station for collection of sorted waste fractions and its delivery to the targeted market such as recycling industries, biogas plants, composting facilities etc. The management efficiency and effectiveness of Waste Bank depend strongly on the proficient sorting and collection of solid waste fractions at household level. However, the social attitude towards such a solution in semi urban/rural areas of Pakistan demands certain prerequisites to make it workable. Considering these factors the objectives of this study are to: [A] Obtain reliable data about quantity and characteristics of generated waste to define feasibility of business and design factors, such as required storage area, retention time, transportation frequency of the system etc. [B] Analyze the effects of various social factors on waste generation to foresee future projections. [C] Quantify the improvement in waste sorting efficiency after awareness campaign. We selected Gujrat city of Central Punjab province of Pakistan as it is semi urban adjoined by rural areas. A total of 60 houses (20 from each of the three selected colonies), belonging to different social status were selected. Awareness sessions about waste segregation were given through brochures and individual lectures in each selected household. Sampling of waste, that households had attempted to sort, was then carried out in the three colored bags that were provided as part of the awareness campaign. Finally, refined waste sorting, weighing of various fractions and measurement of dry mass was performed in environmental laboratory using standard methods. It was calculated that sorting efficiency of waste improved from 0 to 52% as a result of the awareness campaign. The generation of waste (dry mass basis) on average from one household was 460 kg/year whereas per capita generation was 68 kg/year. Extrapolating these values for Gujrat Tehsil, the total waste generation per year is calculated to be 101921 tons dry mass (DM). Characteristics found in waste were (i) organic decomposable (29.2%, 29710 tons/year DM), (ii) recyclables (37.0%, 37726 tons/year DM) that included plastic, paper, metal and glass, and (iii) trash (33.8%, 34485 tons/year DM) that mainly comprised of polythene bags, medicine packaging, pampers and wrappers. Waste generation was more in colonies with comparatively higher income and better living standards. In future, data collection for all four seasons and improvements due to expansion of awareness campaign to educational institutes will be quantified. This waste management system can potentially fulfill vital sustainable development goals (e.g. clean water and sanitation), reduce the need to harvest fresh resources from the ecosystem, create business and job opportunities and consequently solve one of the most pressing environmental issues of the country.

Keywords: integrated solid waste management, waste segregation, waste bank, community development

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Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

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Authors: Sharon Millen, Sarah Miller, Laura Dunne, Clare McGeady, Laura Neeson

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This paper presents the findings from a randomised controlled trial (RCT) and process evaluation of the Lifestart parenting programme. Lifestart is a structured child-centred programme of information and practical activity for parents of children aged from birth to five years of age. It is delivered to parents in their own homes by trained, paid family visitors and it is offered to parents regardless of their social, economic or other circumstances. The RCT evaluated the effectiveness of the programme and the process evaluation documented programme delivery and included a qualitative exploration of parent and child outcomes. 424 parents and children participated in the RCT: 216 in the intervention group and 208 in the control group across the island of Ireland. Parent outcomes included: parental knowledge of child development, parental efficacy, stress, social support, parenting skills and embeddedness in the community. Child outcomes included cognitive, language and motor development and social-emotional and behavioural development. Both groups were tested at baseline (when children were less than 1 year old), mid-point (aged 3) and at post-test (aged 5). Data were collected during a home visit, which took two hours. The process evaluation consisted of interviews with parents (n=16 at baseline and end-point), and focus groups with Lifestart Coordinators (n=9) and Family Visitors (n=24). Quantitative findings from the RCT indicated that, compared to the control group, parents who received the Lifestart programme reported reduced parenting-related stress, increased knowledge of their child’s development, and improved confidence in their parenting role. These changes were statistically significant and consistent with the hypothesised pathway of change depicted in the logic model. There was no evidence of any change in parents’ embeddedness in the community. Although four of the five child outcomes showed small positive change for children who took part in the programme, these were not statistically significant and there is no evidence that the programme improves child cognitive and non-cognitive skills by immediate post-test. The qualitative process evaluation highlighted important challenges related to conducting trials of this magnitude and design in the general population. Parents reported that a key incentive to take part in study was receiving feedback from the developmental assessment, which formed part of the data collection. This highlights the potential importance of appropriate incentives in relation to recruitment and retention of participants. The interviews with intervention parents indicated that one of the first changes they experienced as a result of the Lifestart programme was increased knowledge and confidence in their parenting ability. The outcomes and pathways perceived by parents and described in the interviews are also consistent with the findings of the RCT and the theory of change underpinning the programme. This hypothesises that improvement in parental outcomes, arising as a consequence of the programme, mediate the change in child outcomes. Parents receiving the Lifestart programme reported great satisfaction with and commitment to the programme, with the role of the Family Visitor being identified as one of the key components of the programme.

Keywords: parent-child relationship, parental self-efficacy, parental stress, school readiness

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Authors: Mustafa Metin Donma, Orkide Donma

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Childhood obesity is an important clinical problem because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21), and fetuin-A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver-derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21, and fetuin-A in childhood obesity, to point out possible differences between the obesity groups, and to investigate possible associations among these three hepatokines in obese and morbidly obese children. A total of one hundred and thirty-two children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean ± SD values of ages. Body mass index values of obese and morbidly obese groups were 25.0 ± 3.5 kg/m² and 29.8 ± 5.7 kg/m², respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants. The ethics committee of the institution approved the study protocol. Blood samples were obtained after overnight fasting. Routine biochemical tests, including glucose- and lipid-related parameters, were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study was performed by SPSS for Windows. Statistical difference was accepted significant when p is smaller than 0.05. Statistically significant differences were found for insulin, triglyceride, high-density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbidly obese group. Higher adropin and fetuin-A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbidly obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin-A (r=0.373, p=0.001). In conclusion, increased levels observed in adropin, FGF-21, and fetuin-A have shown that these hepatokines possess increasing potential going from obese to morbid obese state. Out of the correlations found with the IR index, the most affected hepatokine was fetuin-A, the parameter possibly used as the indicator of the advanced obesity stage.

Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity

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