Search results for: early mobilisation in intensive care (ICU)

Authors: Aryati Yashadhana, Ted Fields Jnr., Wendy Fernando, Kelvin Brown, Godfrey Blitner, Francis Hayes, Ruby Stanley, Brian Donnelly, Bridgette Jerrard, Anthea Burnett, Anthony B. Zwi

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Indigenous Australians experience some of the worst health outcomes globally, with life expectancy being significantly poorer than those of non-Indigenous Australians. This is largely attributed to preventable diseases such as diabetes (prevalence 39% in Indigenous Australian adults > 55 years), which is attributed to a raised risk of diabetic visual impairment and cataract among Indigenous adults. Our study aims to explore the interface between structural and sociocultural determinants and human agency, in order to understand how they impact (1) accessibility of eye health and chronic disease services and (2) the potential for Indigenous patients to achieve positive clinical eye health outcomes. We used Participatory Action Research methods, and aimed to privilege the voices of Indigenous people through community collaboration. Semi-structured interviews (n=82) and patient focus groups (n=8) were conducted by Indigenous Community-Based Researchers (CBRs) with diabetic Indigenous adults (> 40 years) in four remote communities in Australia. Interviews (n=25) and focus groups (n=4) with primary health care clinicians in each community were also conducted. Data were audio recorded, transcribed verbatim, and analysed thematically using grounded theory, comparative analysis and Nvivo 10. Preliminary analysis occurred in tandem with data collection to determine theoretical saturation. The principal investigator (AY) led analysis sessions with CBRs, fostering cultural and contextual appropriateness to interpreting responses, knowledge exchange and capacity building. Identified themes were conceptualised into three spheres of influence: structural (health services, government), sociocultural (Indigenous cultural values, distrust of the health system, ongoing effects of colonialism and dispossession) and individual (health beliefs/perceptions, patient phenomenology). Permeating these spheres of influence were three core determinants: economic disadvantage, health literacy/education, and cultural marginalisation. These core determinants affected accessibility of services, and the potential for patients to achieve positive clinical outcomes at every level of care (primary, secondary, tertiary). Our findings highlight the clinical realities of institutionalised and structural inequities, illustrated through the lived experiences of Indigenous patients and primary care clinicians in the four sampled communities. The complex determinants surrounding inequity in health for Indigenous Australians, are entrenched through a longstanding experience of cultural discrimination and ostracism. Secure and long term funding of Aboriginal Community Controlled Health Services will be valuable, but are insufficient to address issues of inequity. Rather, working collaboratively with communities to build trust, and identify needs and solutions at the grassroots level, while leveraging community voices to drive change at the systemic/policy level are recommended.

Keywords: indigenous, Australia, culture, public health, eye health, diabetes, social determinants of health, sociology, anthropology, health equity, aboriginal and Torres strait islander, primary care

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Authors: Sinead Impey, Gaye Stephens, Lucy Hederman, Declan O'Sullivan

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Continued paper use in the clinical area post-Electronic Health Record (EHR) adoption is regularly linked to hardware and software usability challenges. Although paper is used as a workaround to circumvent challenges, including limited availability of a computer, this perspective does not consider the important role paper, such as the nurses’ handover sheet, play in practice. The purpose of this study is to confirm the hypothesis that paper use post-EHR adoption continues as paper provides both a cognitive tool (that assists with workflow) and a compensation tool (to circumvent usability challenges). Distinguishing the different motivations for continued paper-use could assist future evaluations of electronic record systems. Methods: Qualitative data were collected from three clinical care environments (ICU, general ward and specialist day-care) who used an electronic record for at least 12 months. Data were collected through semi-structured interviews with 22 nurses. Data were transcribed, themes extracted using an inductive bottom-up coding approach and a thematic index constructed. Findings: All nurses interviewed continued to use paper post-EHR adoption. While two distinct motivations for paper use post-EHR adoption were confirmed by the data - paper as a cognitive tool and paper as a compensation tool - further finding was that there was an overlap between the two uses. That is, paper used as a compensation tool could also be adapted to function as a cognitive aid due to its nature (easy to access and annotate) or vice versa. Rather than present paper persistence as having two distinctive motivations, it is more useful to describe it as presenting on a continuum with compensation tool and cognitive tool at either pole. Paper as a cognitive tool referred to pages such as nurses’ handover sheet. These did not form part of the patient’s record, although information could be transcribed from one to the other. Findings suggest that although the patient record was digitised, handover sheets did not fall within this remit. These personal pages continued to be useful post-EHR adoption for capturing personal notes or patient information and so continued to be incorporated into the nurses’ work. Comparatively, the paper used as a compensation tool, such as pre-printed care plans which were stored in the patient's record, appears to have been instigated in reaction to usability challenges. In these instances, it is expected that paper use could reduce or cease when the underlying problem is addressed. There is a danger that as paper affords nurses a temporary information platform that is mobile, easy to access and annotate, its use could become embedded in clinical practice. Conclusion: Paper presents a utility to nursing, either as a cognitive or compensation tool or combination of both. By fully understanding its utility and nuances, organisations can avoid evaluating all incidences of paper use (post-EHR adoption) as arising from usability challenges. Instead, suitable remedies for paper-persistence can be targeted at the root cause.

Keywords: cognitive tool, compensation tool, electronic record, handover sheet, nurse, paper persistence

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Authors: E. Prema

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Biotechnology is a study relating to the practical application of living beings in different fields. Generally, it is a study with regard to living organisms in the industrial utilization. It is the technology, which uses living organisms or its parts for specific commercial use. Modification and application of living beings for different practical purposes is possible through biotechnology. Furthermore, today biotechnology is being used in different fields for better results. It is worthwhile to note here that biotechnology is one of the most innovative and intensive industries. It has used the genetically based characteristics in microorganisms, plants and animals to create drugs and to develop drug therapies, which may prevent, cure or alleviate disease and their symptoms. Drugs are basically chemicals and while patenting drugs, the conditions of patentability of chemicals and the types that can be patented are equally applicable to drugs also. Nowadays, the role of biotechnology for manufacturing drugs has assumed much importance because of intellectual property rights. By way using biotechnology, most of the pharmaceutical inventions are getting protection for the period of 20 years as per the Patents Act, 1970 as amended in 2005. There is no doubt that biotechnology is serving the public at large with regard manufacturing drugs and helping the needy people on time.

Keywords: biotechnology, drugs, intellectual property rights, patents

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Authors: Hai Zeng, Yisheng Li, Jincheng Huang, Chenghui Huang, Ying Zhang

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Children are strong; the country strong, the development of children Basketball is a strategic advantage. Common forms of basketball equipment has been difficult to meet the needs of young children teaching the game of basketball, basketball development for 3-6 years old children in the form of appropriate teaching aids is a breakthrough basketball game teaching children bottlenecks, improve teaching critical path pleasure, but also the development of early childhood basketball a necessary requirement. In this study, literature, questionnaires, focus group interviews, comparative analysis, for domestic and foreign use of 12 kinds of basketball teaching aids (cloud computing MINI basketball, adjustable basketball MINI, MINI basketball court, shooting assist paw print ball, dribble goggles, dribbling machine, machine cartoon shooting, rebounding machine, against the mat, elastic belt, ladder, fitness ball), from fun and improve early childhood shooting technique, dribbling technology, as well as offensive and defensive rebounding against technology conduct research on conversion technology. The results show that by using appropriate forms of teaching children basketball aids, can effectively improve children's fun basketball game, targeted to improve a technology, different types of aids from different perspectives enrich the connotation of children basketball game. Recommended for children of color psychology, cartoon and environmentally friendly material production aids, and increase research efforts basketball aids children, encourage children to sports teachers aids applications.

Keywords: health and physical education field of curriculum outline, health fitness, sports and health curriculum reform, Taiwan, twelve years basic education

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Authors: Chimuanya Osuji, Kido Uyamasi, Morgan Bradley

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Introduction: Obesity is a major risk factor for many chronic diseases, with higher rates occurring among certain populations. Even though disparities in obesity rates exist for those with disabilities, few studies have assessed the association between disability and obesity status. This study aims to examine the association between type of disability and obesity status among US adults during the Covid-19 pandemic (2019-2021). Methods: Data for this cross-sectional study was obtained from the 2019, 2020 and 2021 NHIS. Multinomial logistic regressions were used to assess the relationship between each type of disability and obesity status (reference= normal/underweight). Each model adjusted for demographic, health status and health-related quality of life variables. Statistical analyses were conducted using SAS version 9.4. Results: Of the 82,632 US adults who completed the NHIS in 2019, 2020, and 2021. 8.9% (n= 7,354) reported at least 1 disability-related condition. Respondents reported having a disability across vision (1.5%), hearing (1.5%), mobility (5.3%), communication (0.8%), cognition (2.4%) and self-care (1.1%) domains. After adjusting for covariates, adults with at least 1 disability-related condition were about 30% more likely to have moderate-severe obesity (AOR=1.3; 95% CI=1.11, 1.53). Mobility was the only disability category positively associated with mild obesity (AOR=1.16; 95% CI=1.01, 1.35) and moderate/severe obesity (AOR=1.6; 95% CI=1.35, 1.89). Individuals with vision disability were about 35% less likely to have mild obesity (AOR=0.66; 95% CI=0.51, 0.86) and moderate-severe obesity (AOR=0.66; 95% CI= 0.48, 0.9). Individuals with hearing disability were 28% less likely to have mild obesity (AOR=0.72; 95% CI= 0.56, 0.94). Individuals with communication disability were about 30% less likely to be overweight (AOR=0.66; 95% CI=0.47, 0.93) and 50% less likely to have mild obesity (AOR=0.45; 95% CI= 0.29, 0.71). Individuals with cognitive disability were about 25% less likely to have mild obesity and about 35% less likely to have moderate-severe obesity. Individuals with self-care disability were about 30% less likely to be overweight. Conclusion: Mobility-related disabilities are significantly associated with obesity status among adults residing in the United States. Researchers and policy makers should implement obesity intervention methods that can address the gap in obesity prevalence rates among those with and without disabilities.

Keywords: cognition, disability, mobility, obesity

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Authors: Meinrad Haule Lembuka

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Ubuntu is an African philosophy and model with the meaning of 'humanity to others' or 'care for other’s needs because of the guiding principle of interdependence’ that embraces collective and holistic efforts in development through the human face. The study uses a literature review method reflecting Julius Nyerere’s contributions in realizing Ubuntu and social work practice. Nyerere strived to restore Africa development in the lens of humanism through the values of solidarity, communal participation, compassion, care, justice etc; He later founded developmental social work through Ujamaa model, educational for self reliance and African dignity. Nyerere was against post-colonial syndromes through African socialism that envisioned values and principles of social work to provide social justice, human dignity, social change and social development. Also, he managed to serve the primary mission of the social work profession to enhance human wellbeing and help meet basic human needs of all people, with particular attention to the needs and empowerment of people who are vulnerable, oppressed, and living in poverty with African Ubuntu practice of equal distribution of resources. Nyerere further endorsed social work legal framework that embraced universal human rights: service, equality, social justice, and human dignity, Importance of human relationship, integrity and competence. Nyerere proved that Indigenous model can work with formal system like Social work profession. In 2014 the National Heritage Council of South Africa (NHC) honored him an Award of African Ubuntu champion. Nyerere strongly upheld to be an ambassador of social work through his remarkably contributions in developmental social work (Ujamaa model), social change, human dignity, equality, social unity and social justice in Africa and globe at large.

Keywords: ubuntu, Indiginious knowledge, Indiginious social work, ubuntu social work

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Authors: Shu Hwang Ang, Choo Yee Yu, Geik Yong Ang, Yean Yean Chan, Yatimah Binti Alias, And Sook Mei Khor

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With the high prevalence of Type 2 diabetes mellitus across the world, the morbidities and mortalities associated with Type 2 diabetes have significant impact on the production line for a nation. With routine scheduled clinical visits to manage Type 2 diabetes, diabetic patients with hectic lifestyles can have low clinical compliance. Hence, it often decreases the effectiveness of diabetic management personalized for each diabetic patient. Here, we report a useful developed point-of-care (POC) device that detect glycated hemoglobin (HbA1c, biomarker for long-term Type 2 diabetic management). In fact, the established POC devices certified to be used in clinical setting are not only expensive ($ 8 to $10 per test), they also require skillful practitioners to perform sampling and interpretation. As a paper-based biosensor, the developed HbA1c biosensor utilized lateral flow principle to offer an alternative for cost-effective (approximately $2 per test) and end-user friendly device for household testing. Requiring as little as 2 L of finger-picked blood, the test can be performed at the household with just simple dilution and washings. With visual interpretation of numbers of test lines shown on the developed biosensor, it can be interpreted as easy as a urine pregnancy test, aided with scale of intensity provided. In summary, the developed HbA1c immunosensor has been tested to have high selectivity towards HbA1c, and is stable with reasonably good performance in clinical testing. Therefore, our developed HbA1c immunosensor has high potential to be an effective diabetic management tool to increase patient compliance and thus contain the progression of the diabetes.

Keywords: blood, glycated hemoglobin (HbA1c), lateral flow, type 2 diabetes mellitus

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Authors: Muqadis Shazia Rajpar, Lawrence Mitelberg, Rubaiat S. Ahmed, Jemer Garrido, Rukhsana Hossain, Sergey M. Motov

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Distraction techniques have been used as a means to reduce pain, anxiety, and stress in various healthcare settings to facilitate care and make visits less unpleasant. Using virtual reality (VR) in the pediatric emergency setting can be a valuable, effective, and safe non-pharmacological alternative to the current standard of care for pain and anxiety management in pediatric patients. Our pilot study aimed to evaluate the effectiveness of a VR-based intervention as an alternative distraction modality to alleviate pain and anxiety associated with pediatric emergency department (ED) visits and acute pain conditions. The pilot study period was from November 16 to December 9, 2022, for pediatric ED visits for pain, anxiety, or both. Patients were selected based on a novel VR protocol to receive the VR intervention with the administration of pre and post-intervention surveys concerning pain/anxiety ratings and pain scores (Wong-Baker FACES/NRS). Descriptive statistics, paired t-test, and a Fisher Exact Test were used for data analysis, assuming a p-value of 0.05 for significance. A total of 33 patients (21 females, 12 males), ages 5-20 (M = 10.5, SD = 3.43) participated in this study – 12 patients had pain, 2 patients had anxiety, and 19 patients had both pain and anxiety. There was a statistically significant decrease in post-intervention pain scores of less than one point on the rating scale (6.48 vs. 5.62, p < .001). There was a statistically significant reduction in the percentage of patients suffering from “considerable” or “great” pain after the VR intervention (51.6% to 42.3%, p < .001). Similarly, we noticed an increase in the number of patients with “slight” or “moderate” pain post–VR intervention (48.4% to 57.7%, p < .001). Lastly, we demonstrated a decrease in anxiety among patients after utilizing VR (63.6% vs. 36.4%, p < .001). To conclude, VR can alleviate pain and anxiety in pediatric patients and be a useful non-pharmacological tool in the emergency setting.

Keywords: anxiety, emergency room, pain management, pediatric emergency medicine, virtual reality

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Authors: S. S. Singh, A. Bhattacharya, S. Bhattacharya

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The eukaryotic exosome complex plays a pivotal role in RNA biogenesis, maturation, surveillance and differential expression of various RNAs in response to varying environmental signals. The exosome is composed of evolutionary conserved nine core subunits and the associated exonucleases Rrp6 and Rrp44. Rrp6p is crucial for the processing of rRNAs, other non-coding RNAs, regulation of polyA tail length and termination of transcription. Rrp6p, a 3’-5’ exonuclease is required for degradation of 5’-external transcribed spacer (ETS) released from the rRNA precursors during the early steps of pre-rRNA processing. In the parasitic protist Entamoeba histolytica in response to growth stress, there occurs the accumulation of unprocessed pre-rRNA and 5’ ETS sub fragment. To understand the processes leading to this accumulation, we looked for Rrp6 and the exosome subunits in E. histolytica, by in silico approaches. Of the nine core exosomal subunits, seven had high percentage of sequence similarity with the yeast and human. The EhRrp6 homolog contained exoribonuclease and HRDC domains like yeast but its N- terminus lacked the PMC2NT domain. EhRrp6 complemented the temperature sensitive phenotype of yeast rrp6Δ cells suggesting conservation of biological activity. We showed 3’-5’ exoribonuclease activity of EhRrp6p with in vitro-synthesized appropriate RNAs substrates. Like the yeast enzyme, EhRrp6p degraded unstructured RNA, but could degrade the stem-loops slowly. Furthermore, immunolocalization revealed that EhRrp6 was nuclear-localized in normal cells but was diminished from nucleus during serum starvation, which could explain the accumulation of 5’ETS during stress. Our study shows functional conservation of EhRrp6p in E.histolytica, an early-branching eukaryote, and will help to understand the evolution of exosomal components and their regulatory function.

Keywords: entamoeba histolytica, exosome complex, rRNA processing, Rrp6

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Authors: Nazihe Sedighi, Mohsen Nokhbatolphoghaei

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Bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics. Due to having properties such as transparency, heat and impact resistance, it is used widely in medicine, sorts, electronic components, and food containers. It is also used in the production of resins which is applied for lining cans. BPA releases from resins and polycarbonate when it is heated or continuously used the containers from which BPA can enter the body. There are several reports indicating the presence of BPA in the placenta, amniotic fluid, and the embryo itself. While researchers investigated the teratogenic effect of BPA on embryos, very limited work has been done on the effects of BPA when applied from early stages of development. In this study, The teratogenic effect of BPA was investigated at earliest preimplantation (day zero) through day 15.5 of the development of Balb/C mouse embryos. After ensuring the pregnancy via observing vaginal plug, Pregnant mice were divided into five groups. For the three experimental groups, the amount of 500, 750, and 1000 mg/kg/d Bisphenol A was given orally according to body weight. The sham group that was treated with sesame oil, which was used as vehicle and control group remained intact. On day 18.5 of gestation, embryos were removed from the uterus. Randomly half of the embryo were fixed in Bouin for tissue analysis. The other half were prepared for skeletal system staining using Alizarin Red and alcian blue dies. The results showed that the embryonic weight and the crown-rump length of embryos decreased significantly (P < 0.05) in all experimental groups compared to the control group and the sham. In this study, skeletal abnormalities such as delay in ossification of skull and limbs as well as the deviation in the backbone were seen. This research suggests that pregnant mothers need to be aware of possible teratogenic effects of BPA at any stage of pregnancy especially from early to mid stages. In this case, pregnant mothers may need to stop using any manufacture of polycarbonate plastics, as a container for food or drinking.

Keywords: bisphenol A, development, polycarbonate plastic, skeletal system, teratogenicity

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Authors: Mykah W. Sumoldao, Maria Erissa C. Susa, Triny Cate M. Telan, Christian Arvin M. Torres, Jasmine I. Udasco, Franceis Jeramil M. Walis, Shellyn S. Wandagan, Janine May M. Warding, Queenie Diana Rose P. Zalun Hope Lulet A. Lomioan

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This descriptive phenomenological study explored the lived experiences of the primary caregiver of schizophrenia patients at the Acute Crisis Intervention Service in Cagayan Valley Medical Center. The research aimed to understand the emotional, physical, and financial challenges these primary caregivers face. Data was gathered through interviews with nine (9) primary caregivers and analyzed using Colaizzi’s seven-step method. Two main themes emerged: Experience/ Challenges (Emotional, Physical, and Financial Challenges) and Managing Mechanisms (Support Systems and Resilience and Commitment). The study found that primary caregivers deal with a complex mix of difficulties, often with limited resources. They rely heavily on personal strength, faith, family, friends and community support to manage their roles. The findings highlighted the need for better support systems to ease primary caregivers' burdens. Financial aid, respite care, and mental health support are crucial for improving primary caregivers' quality of life and the care they provide. Additionally, raising awareness about primary caregivers' challenges can foster a supportive community, with more help from local organizations and government entities. Thus, this study provided insights into the caregiving experiences of those supporting schizophrenia patients. It emphasized the importance of practical support and emotional resilience. By addressing these needs, a more supportive environment can be created, benefiting both primary caregivers and their patients.

Keywords: primary caregiver burden, mental health, primary caregiver well-being, primary caregiver

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Authors: Vaiyapuri Subbarayn Periasamy, Jegan Athinarayanan, Ali A. Alshatwi

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The widespread use of Titanium oxide nanoparticles (TiO2-NPs), now are found with different physic-chemical properties (size, shape, chemical properties, agglomeration, etc.) in many processed foods, agricultural chemicals, biomedical products, food packaging and food contact materials, personal care products, and other consumer products used in daily life. Growing evidences have been highlighted that there are risks of physico-chemical properties dependent toxicity with special attention to “TiO2-NPs and human immune system”. Unfortunately, agglomeration and aggregation have frequently been ignored in immuno-toxicological studies, even though agglomeration and aggregation would be expected to affect nanotoxicity since it changes the size, shape, surface area, and other properties of the TiO2-NPs. In this present investigation, we assessed the immune toxic effect of TiO2-NPs on human immune cells Total WBC including Lymphocytes (T cells (CD3+), T helper cells (CD3+, CD4+), Suppressor/cytotoxic T cells (CD3+/CD8+) and NK cells (CD3-/CD16+ and CD56+), Monocytes (CD14+, CD3-) and B lymphocytes (CD19+, CD3-) in order to find the immunological response (IL1A, IL1B, IL2 IL-4, IL5 IL-6, IL-10, IL-12, IL-13, IFN-γ, TGF-β, and TNF-a) and redox gene regulation (TNF, p53, BCl-2, CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1)-linking physicochemical properties with special reference to agglomeration of TiO2-NPs. Our findings suggest that TiO2-NPs altered cytokine production, enhanced phagocytic indexing, metabolic stress through specific immune regulatory- genes expression in different WBC subsets and may contribute to pro-inflammatory response. Although TiO2-NPs have great advantages in the personal care products, biomedical, food and agricultural products, its chronic and acute immune-toxicity still need to be assessed carefully with special reference to food and environmental safety.

Keywords: TiO2 nanoparticles, oxidative stress, cytokine, human immune cells

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Authors: Andrew Read, Alice Parry, Kate Woods

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Since the advent of the SARS-CoV-2 pandemic, the search for medications that can reduce mortality and morbidity has been a global research priority. Several multi-center trials have recently demonstrated improved mortality associated with the use of Tocilizumab, an interleukin-6 receptor antagonist, in patients with severe SARS-CoV-2 pneumonia. Initial data supported the administration in patients requiring respiratory support (non-invasive or invasive ventilation), but more recent data has shown benefit in all hypoxic patients. At the height of the second wave of COVID-19 infections in London, our hospital introduced the use of Tocilizumab for patients with severe COVID-19. Tocilizumab is licensed for use in chronic inflammatory conditions and has been associated with an increased risk of severe bacterial and fungal infections, as well as reactivation of chronic viral infections (e.g., hepatitis B). It is a specialist drug that suppresses the formation of C-reactive protein (CRP) for 6 – 12 weeks. It is not widely used by the general medical community. We aimed to assess Tocilizumab use in our hospital and to implement changes to the protocol as required to ensure administration was safe and appropriate. A retrospective study design was used to assess prescriptions over an initial 3-week period in both intensive care and on the medical wards. This amounted to a total of 13 patients. The initial data collection identified four key areas of concern: adherence to national and local inclusion & exclusion criteria; a collection of appropriate screening blood prior to administration; documentation of informed consent or best interest decision and documentation of Tocilizumab administration on patient discharge information, to alert future healthcare providers that typical measures of inflammation and infection, such as CRP, are unreliable for up to 3-months. Data were collected from electronic notes, blood results and observation charts, and cross referenced with pharmacy data. Initial results showed that all four key areas were completed in approximately 50% of cases. Of particular concern was adherence to exclusion criteria, such as current evidence of bacterial infection, and ensuring the correct screening blood was sent to exclude infections such as hepatitis. To remedy this and improve patient safety, the initial data was presented to relevant healthcare professionals. Subsequently, three interventions were introduced and education on each provided to hospital staff. An electronic ‘order set’ collating the appropriate screening blood was created simplifying the screening process. Pre-formed electronic documentation which can be inserted into the notes was created to provide a framework for consent discussions and reduce the time needed for junior doctors to complete this task. Additionally, a ‘Tocilizumab’ administration card was created and administered via pharmacy. This was distributed to each patient on discharge to ensure future healthcare professionals were aware of the potential effects of Tocilizumab administration, including suppression of CRP. Following these changes, repeat data collection over two months illustrated that each of the 4 safety aspects was met with a 100% success rate in every patient. Although this demonstrates good progress and effective interventions the challenge will be to maintain this progress. The audit data collection is ongoing

Keywords: education, patient safety , SARS-CoV-2, Tocilizumab

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Authors: C. A. Sharma, Birendra P. Singh

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We recovered 40 well preserved ribbon-shaped, meandering specimens of S. ningqiangensis from the Earthy Dolomite Member (Krol Group) and calcareous siltstone beds of the Earthy Siltstone Member (Tal Group) showing closely spaced annulations that lacked branching. The beginning and terminal points are indistinguishable. In certain cases, individual specimens are characterized by irregular, low-angle to high-angle sinuosity. It has been variously described as body fossil, ichnofossil and algae. Detailed study of this enigmatic fossil is needed to resolve the long standing controversy regarding its phylogenetic and stratigraphic placements, which will be an important contribution to the evolutionary history of metazoans. S. ningqiangensis has been known from the late Neoproterozoic (Ediacaran) of southern and central China (Sichuan, Shaanxi, Quinghai and Guizhou provinces and Ningxia Hui Autonomous region), Siberian platform and across Pc/C Boundary from latest Neoprterozoic to earliest Cambrian of northern India. Shaanxilithes is considered an Ediacaran organism that spans the Precambrian–Cambrian boundary, an interval marked by significant taphonomic and ecological transformations that include not only innovation but also probable extinction. All the past well constrained finds of S. ningqiangensis are restricted to Ediacaran age. However, due to the new recoveries of the fossil from Nigalidhar Syncline, the stratigraphic status of S. ningqiangensis-bearing Earthy Siltstone Member of the Shaliyan Formation of the Tal Group (Cambrian) is rendered uncertain, though the overlying Chert Member in the adjoining Korgai Syncline has yielded definite early Cambrian acritarchs. The moot question is whether the Earthy Siltstone Member represents an Ediacaran or an early Cambrian age?. It would be interesting to find if Shaanxilithes, so far known from Ediacaran sequences, could it transgress to the early Cambrian or in simple words could it withstand the Pc/C Boundary event? GC-MS data shows the S. ningqiangensis structure is formed by hydrocarbon organic compounds which are filled with inorganic elements filler like silica, Calcium, phosphorus etc. The S. ningqiangensis structure is a mixture of organic compounds of high molecular weight, containing several saturated rings with hydrocarbon chains having an occasional isolated carbon-carbon double bond and also containing, in addition, to small amounts of nitrogen, sulfur and oxygen. Data also revealed that the presence of nitrogen which would be either in the form of peptide chains means amide/amine or chemical form i.e. nitrates/nitrites etc. The formula weight and the weight ratio of C/H shows that it would be expected for algae derived organics, since algae produce fatty acids as well as other hydrocarbons such as cartenoids.

Keywords: GC-MS Analysis, lesser himalaya, Pc/C Boundary, shaanxilithes

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Authors: Ndarusanze Berchmans

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This research work focused on the analysis of the observations of tuberculous meningitis in HIV-positive patients who were treated by the Prince Regent Charles Hospital in Bujumbura. A number of 246 seropositive patients were examined by the laboratory of Prince Regent Charles in the period between 2010 and 2015. We did a retrospective study; we used data from the registers of the laboratories mentioned above; the objective was to approach the epidemiological, biological, clinical, and therapeutic characteristics of tuberculosis meningitis infection: 124 women (50.40% of AIDS patients) and 122 men (49.59% of AIDS patients) were subject to the diagnosis by identification of cerebrospinal fluid (CSF). The average age of the patients was 30 years for this period. The population at risk has an average age of between 34 and 42 years for the years between 2010-2015. From 2010 to 2012, cases of opportunistic diseases (e.g., tuberculous meningitis and Cryptococcus neoformans meningitis), often found in immunocompromised, were observed at a high rate; in this period, there was a disturbance of the rhythm providing antiretroviral drugs to people with AIDS. The rate of the two meningitis (tuberculous meningitis and Cryptococcus neoformans meningitis) remained above 10% to gradually decrease until 2015, with the gradual return of antiretrovirals. This period records an overall average of 25 cases of tuberculous meningitis, or a percentage of 10.16%. For the year 2015, there were 4 cases of tuberculous meningitis out of a total of 35 seropositive examined (11.42%). This year's percentage shows that the number of tuberculous meningitis cases has fallen from the rate in previous years. This is the result of the care given by associations against HIV/AIDS to HIV-positive people. This decrease in cases of tuberculous meningitis is due to the acquisition of antiretrovirals by all HIV-positive people treated by hospitals. For the moment, these hospitals are taking care of many AIDS patients by providing them permanently with antiretrovirals; Besides that, there are many patients who are supported by associations whose activities are directed against HIV/AIDS.

Keywords: Cryptococcus neoformans meningitis, tuberculosis meningitis, neurological complications, epidemiology of meningitis

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Authors: Paulo Cumbe

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This work analyzes the economic and environmental impact of the exploitation of forest resources on populations and their sustainability in the regions where it occurs. There is an intensive and continuous activity of charcoal production, in the Massingir and Mabalane districts, in Gaza, Mozambique, to supply the most used fuel that is used by the population of the capital city, Maputo. Charcoal production is one of the sources of income for several families. However, it causes a negative environmental impact on biodiversity. We have analyzed different studies carried out in these communities that measure the speed, the level, and the impact of deforestation involving different actors, to deepen our understanding of this issue. The results of these studies reveal that the degraded area in five years would need one hundred years to be restored, which is unsustainable from an environmental point of view it is. Populations seek new areas for the same practice to maintain their livelihood, progressing with ecosystem degradation and increasing carbon dioxide emissions into the atmosphere. It is believed that environmental education, creation, and dissemination of new forms of charcoal production that are more profitable and less aggressive to the environment and forest repopulation actions need to be carried out to guarantee the sustainable development of the populations in these regions.

Keywords: deforestation, emissions, sustainability, charcoal

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Authors: Arun Sanjel, Greg Speegle

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Every second, massive amounts of data are generated, and Data Intensive Scalable Computing (DISC) frameworks have evolved into effective tools for analyzing such massive amounts of data. Since the underlying architecture of these distributed computing platforms is often new to users, building a DISC application can often be time-consuming and prone to errors. The automated conversion of a sequential program to a DISC program will consequently significantly improve productivity. However, synthesizing a user’s intended program from an input specification is complex, with several important applications, such as distributed program synthesizing and code refactoring. Existing works such as Tyro and Casper rely entirely on deductive synthesis techniques or similar program synthesis approaches. Our approach is to develop a data-driven synthesis technique to identify sequential components and translate them to equivalent distributed operations. We emphasize using reinforcement learning and unit testing as feedback mechanisms to achieve our objectives.

Keywords: program synthesis, distributed computing, reinforcement learning, unit testing, DISC

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Authors: Hussain Ali, Ahmad Ali, Syed Rashid Ali

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The maternal mortality is one of the basic health issues faced by rural women in Pakistan. There are various structural and socio-cultural determinants which confine women to domestic sphere. Such mobility restriction compels women for home delivery which causes high maternal mortality and morbidity. However, it is hard to find out the research findings and well-organized literature that explain the cultural factors act as determinant to home delivery among Pakhtun women. The overall objective of this research is to study men’s decision making within the household in Pakhtun society as determinant of home delivery among Pakhtun women in Khyber Pakhtunkhwa province of Pakistan. In the present study, researchers used the quantitative research design in which the data are collected through household survey technique from (n=503) ever-married women having reproductive age (15-49 years) by using interview schedule. The data are analyzed through SPSS, and binary logistic regression was applied to draw the association between home as a place of delivery and men’s decision making in the Pakhtun society. The results show that majority (76%) of the husbands are key decision makers about the home delivery due to their superior position within household. Similarly, majority (88%) Pakhtun women prefer to stay in home for their delivery due to their dependency on husband’s decision. The researcher concludes that men are key decision makers in Pakhtun society and their decisions affect women maternal health care. Similarly, the women are in subordinate position, and their limited decision making in the domestic sphere are greatly responsible for home delivery which causing high maternal mortality rate in the study area. In order to achieve Sustainable Development Goal No. 3, the study recommends empowering women in the decision making about accessing and utilizing maternal health care services and given financial autonomy to them.

Keywords: home delivery, men’s decision, Pakhtun women, subordinate position

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Authors: Sanaz Moayer, Fang Huang, Scott Gardner

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In the highly leveraged business world of today, an organisation’s success depends on how it can manage and organize its traditional and intangible assets. In the knowledge-based economy, knowledge as a valuable asset gives enduring capability to firms competing in rapidly shifting global markets. It can be argued that ability to create unique knowledge assets by configuring ICT and human capabilities, will be a defining factor for international competitive advantage in the mid-21st century. The concept of KM is recognized in the strategy literature, and increasingly by senior decision-makers (particularly in large firms which can achieve scalable benefits), as an important vehicle for stimulating innovation and organisational performance in the knowledge economy. This thinking has been evident in professional services and other knowledge intensive industries for over a decade. It highlights the importance of social capital and the value of the intellectual capital embedded in social and professional networks, complementing the traditional focus on creation of intellectual property assets. Despite the growing interest in KM within professional services there has been limited discussion in relation to multinational resource based industries such as mining and petroleum where the focus has been principally on global portfolio optimization with economies of scale, process efficiencies and cost reduction. The Australian minerals and metals mining industry, although traditionally viewed as capital intensive, employs a significant number of knowledge workers notably- engineers, geologists, highly skilled technicians, legal, finance, accounting, ICT and contracts specialists working in projects or functions, representing potential knowledge silos within the organisation. This silo effect arguably inhibits knowledge sharing and retention by disaggregating corporate memory, with increased operational and project continuity risk. It also may limit the potential for process, product, and service innovation. In this paper the strategic application of knowledge management incorporating contemporary ICT platforms and data mining practices is explored as an important enabler for knowledge discovery, reduction of risk, and retention of corporate knowledge in resource based industries. With reference to the relevant strategy, management, and information systems literature, this paper highlights possible connections (currently undergoing empirical testing), between an Strategic Knowledge Management (SKM) framework incorporating supportive Data Mining (DM) practices and competitive advantage for multinational firms operating within the Australian resource sector. We also propose based on a review of the relevant literature that more effective management of soft and hard systems knowledge is crucial for major Australian firms in all sectors seeking to improve organisational performance through the human and technological capability captured in organisational networks.

Keywords: competitive advantage, data mining, mining organisation, strategic knowledge management

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Authors: Abbas Mohammed, Felicitász Velledits

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Evaluating carbonate rocks is crucial for the petroleum industry as they often serve as major hydrocarbon reservoirs, where understanding their depositional and diagenetic characteristics directly influences exploration, production, and field development plans. The Early Cretaceous Yamama carbonates Formation in southern Iraq exhibits significant reservoir but heterogeneous. Detailed sedimentological investigations of drill cores and well logs have identified 14 distinct facies/microfacies within both reservoir and non-reservoir units, deposited in a shallow carbonate ramp setting. The grain-supported facies such as intertidal peloidal oncoidal grain/rudstones, backshoal pelletal pack/grainstones, shoal ooidal-peloidal grainstones, cortoidal-peloidal grainstones, in addition to the Lithocodium-Bacinella float/boundstones, and the reefal skeletal rudstones facies display favorable reservoir properties due to preserved interparticle porosity (reaches 25%) at depths greater than 4000 m. This preservation is attributed to early diagenetic circumgranular calcite cementation and limited scattered equant and syntaxial calcite overgrowths, which protected the grains from physical compaction. In contrast, mud-supported facies such as lagoonal skeletal mud/wackestones, skeletal cortoids wacke/packstones, skeletal dasyclads wacke/packstone, middle-ramp miliolidal pack/grainstone, bioturbated dolomitic wackestones, skeletal foraminiferal mud/wackestones, and outer-ramp spiculitic skeletal mud/wackestones exhibit reduced reservoir quality due to a combination of their fine-grain texture, physical and chemical compaction, and substantial amounts of equant calcite cement. This cement fills interparticle and moldic pores, and significantly reducing porosity and permeability in these facies. Reservoir heterogeneity of the formation is attributed to depositional facies, which control the texture of the sediments, and various types of diagenetic alterations. Particular attention to be directed toward the Lithocodium-Bacinella facies deposited as build-ups and the shoal barrier grain-supported facies. These findings underscore the importance of adapting exploration and development strategies to specific facies distributions and diagenetic pathways to mitigate heterogeneity risks. While potential limitations include the extrapolation of core and well log data to field-scale reservoir modeling and the challenge of investigating diagenetic variations at finer scales, the study provides a valuable framework for integrating facies and diagenetic analysis into hydrocarbon exploration workflows.

Keywords: depositional facies, grain-supported limestones, lithocoduim-bacinella, reservoir heterogeneity, yamama formation

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Authors: Mohammed Yagoub

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The new orientation to the market economy sponsored by the Algeria government in the early Nineties of the last century, and its desire to develop investment mechanisms and the promotion of development recently, the access into a partnership with the European Union, and the forthcoming accession to the World Trade Organization, foreign direct investment makes one of the most important means of opening up to foreign markets and bring technology and interact with globalization, this article we will discuss the impact of FDI on economic growth in the Algerian.

Keywords: economic, development, markets, FDI, displacement, globalization

Procedia PDF Downloads 365

Authors: M. A. Medeiros, A. A. N. Dantas, F. A. N. França, R. F. Amaral

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There are several alternatives of coastal erosion control with geosynthetics. As an important stage of any Civil Engineering project, literature review is necessary in order to evaluate these alternatives and to guide the decisions. Ponta Negra beachfront has a very intensive urban pressure. In addition, a very short sand area induces high intensity erosion processes. Different attempts of solving the problem were already built. However, erosion issues are still an important concern since these structures collapsed. Geosynthetics present a great potential to be applied in this area. In order to study coastal erosion control alternatives with the use of geosynthetics, this paper presents a literature review about this subject. Several studies were collected in which beach conditions are similar to those found in Ponta Negra beach. It was possible to evaluate the alternatives that might be used in the area. Further studies include the application of such techniques in pilot areas and the evaluation of the erosion process. Finally, the best alternative for futures studies on Ponta Negra beach is geocontainers of geotextiles.

Keywords: geosynthetics, coastal erosion control, alternatives, Ponta Negra beach

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Authors: Keigo Nishitani, Kohei Mizuta Mizuta, Kazuyoshi Kurita, Yukinori Taniguchi

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To establish mass production process of Ti capsule which has Fe powder inside as magnetic hyperthermia implant, we assumed that Ti thin sheet can be drawn into a φ1.0 mm die hole through the medium of Fe Powder and becomes outer shell of capsule. This study discusses mechanism of powder assisted deep drawing process by both of numerical simulation and experiment. Ti thin sheet blank was placed on die, and was covered by Fe powder layer without pressurizing. Then upper punch was indented on the Fe powder layer, and the blank can be drawn into die cavity as pressurized powder particles were extruded into die cavity from behind of the drawn blank. Distinct Element Method (DEM) has been used to demonstrate the process. To identify bonding parameters on Fe particles which are cohesion, tensile bond stress and inter particle friction angle, axial and diametrical compression failure test of Fe powder compact was conducted. Several density ratios of powder compacts in range of 0.70 - 0.85 were investigated and relationship between mean stress and equivalent stress was calculated with consideration of critical state line which rules failure criterion in consolidation of Fe powder. Since variation of bonding parameters with density ratio has been experimentally identified, and good agreement has been recognized between several failure tests and its simulation, demonstration of powder assisted sheet forming by using DEM becomes applicable. Results of simulation indicated that indent/drawing length of Ti thin sheet is promoted by smaller Fe particle size, larger indent punch diameter, lower friction coefficient between die surface and Ti sheet and certain degrees of die inlet taper angle. In the deep drawing test, we have made die-set with φ2.4 mm punch and φ1.0 mm die bore diameter. Pure Ti sheet with 100 μm thickness, annealed at 650 deg. C has been tested. After indentation, indented/drawn capsule has been observed by microscope, and its length was measured to discuss the feasibility of this capsulation process. Longer drawing length exists on progressive loading pass comparing with the case of single stroke loading. It is expected that progressive loading has an advantage of which extrusion of powder particle into die cavity with Ti sheet is promoted since powder particle layer can be rebuilt while the punch is withdrawn from the layer in each loading steps. This capsulation phenomenon is qualitatively demonstrated by DEM simulation. Finally, we have fabricated Ti capsule which has Fe powder inside for magnetic hyperthermia cancer care treatment. It is concluded that suggested method is possible to use the manufacturing of Ti capsule implant for magnetic hyperthermia cancer care.

Keywords: metal powder compaction, metal forming, distinct element method, cancer care, magnetic hyperthermia

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Authors: Seyedmohammad Mousavian, Hanlu Fan, Quingliang Tang

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Climate change is emerging as a severe threat to our society, so businesses are expected to take actions to mitigate carbon emissions. However, the actions to be taken depend on managers’ perceptions of climate change risks. Yet, there is scant research on this issue, and understanding of the determinants of corporate perceptions of climate change is extremely limited. The purpose of this study is to close this gap by examining the relationship between perceptions of climate risk and firm-level and country-level factors. In this study, climate change risk captures physical, regulatory, and other risks, and we use data from European companies that participated in CDP from 2010 to 2017. This study reveals those perceptions of climate change risk are significantly positively associated with the environmental, social, and governance score, firm size, and membership in a carbon-intensive sector. In addition, we find that managers in firms operating in a geographic area that is sensitive to the consequences of global warming are more likely to perceive and formally recognize carbon-related risks in their CDP reports.

Keywords: carbon actions, CDP, climate change risk, risk perception

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Authors: Charles Lemckert

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E-Learning and E-Teaching can mean many things to different people. For some, the implication is that all material must be delivered in an E way, while for others it only forms part of the learning/teaching process, and (unfortunately) for some it is considered too much work. However, just look around and you will see all generations learning using E devices. In this study we used different forms of teaching, including E, to look at how students responded to set activities and how they performed academically. The particular context was set around a postgraduate university course where students were either present at a face-to-face intensive workshop (on water treatment plant design) or where they were not. For the latter, students needed to make sole use of E media. It is relevant to note that even though some were at the face-to-face class, they were still exposed to E material as the lecturer did use PC projections. Additionally, some also accessed the associate E material (pdf slides and video recordings) to assist their required activities. Analysis of the student performance, in their set assignment, showed that the actual form of delivery did not affect the student performance. This is because, in the end, all the students had access to the recorded/presented E material. The study also showed (somewhat expectedly) that when the material they required for the assignment was clear, the student performance did drop. Therefore, it is possible to enhance future delivery of courses through careful reflection and appropriate support. In the end, we must remember innovation is not just restricted to E.

Keywords: postgraduate, engineering, assignment, perforamance

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Authors: Martin Hofmann, Diego Stutzer, Thomas Niederhauser, Juergen Burger

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Dental biofilm is the main etiologic factor for caries, periodontal and peri-implant infections. In addition to the risk of tooth loss, periodontitis is also associated with an increased risk of systemic diseases such as atherosclerotic cardiovascular disease and diabetes. For this reason, dental hygienists use ultrasonic scalers for prophylactic and periodontal care of the teeth. However, the current instruments are limited to their dimensions and operating frequencies. The innovative design of a planar ultrasonic transducer introduces a new type of dental scalers. The flat titanium-based design allows the mass to be significantly reduced compared to a conventional screw-mounted Langevin transducer, resulting in a more efficient and controllable scaler. For the development of the novel device, multi-physics finite element analysis was used to simulate and optimise various design concepts. This process was supported by prototyping and electromechanical characterisation. The feasibility and potential of a planar ultrasonic transducer have already been confirmed by our current prototypes, which achieve higher performance compared to commercial devices. Operating at the desired resonance frequency of 28 kHz with a driving voltage of 40 Vrms results in an in-plane tip oscillation with a displacement amplitude of up to 75 μm by having less than 8 % out-of-plane movement and an energy transformation factor of 1.07 μm/mA. In a further step, we will adapt the design to two additional resonance frequencies (20 and 40 kHz) to obtain information about the most suitable mode of operation. In addition to the already integrated characterization methods, we will evaluate the clinical efficiency of the different devices in an in vitro setup with an artificial biofilm pocket model.

Keywords: ultrasonic instrumentation, ultrasonic scaling, piezoelectric transducer, finite element simulation, dental biofilm, dental calculus

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Authors: J. J. Rickard, A. Belli, P. Goldberg Oppenheimer

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Medical diagnostics, environmental monitoring, homeland security and forensics increasingly demand specific and field-deployable analytical technologies for quick point-of-care diagnostics. Although technological advancements have made optical methods well-suited for miniaturization, a highly-sensitive detection technique for minute sample volumes is required. Raman spectroscopy is a well-known analytical tool, but has very weak signals and hence is unsuitable for trace level analysis. Enhancement via localized optical fields (surface plasmons resonances) on nanoscale metallic materials generates huge signals in surface-enhanced Raman scattering (SERS), enabling single molecule detection. This enhancement can be tuned by manipulation of the surface roughness and architecture at the sub-micron level. Nevertheless, the development and application of SERS has been inhibited by the irreproducibility and complexity of fabrication routes. The ability to generate straightforward, cost-effective, multiplex-able and addressable SERS substrates with high enhancements is of profound interest for SERS-based sensing devices. While most SERS substrates are manufactured by conventional lithographic methods, the development of a cost-effective approach to create nanostructured surfaces is a much sought-after goal in the SERS community. Here, a method is established to create controlled, self-organized, hierarchical nanostructures using electrohydrodynamic (HEHD) instabilities. The created structures are readily fine-tuned, which is an important requirement for optimizing SERS to obtain the highest enhancements. HEHD pattern formation enables the fabrication of multiscale 3D structured arrays as SERS-active platforms. Importantly, each of the HEHD-patterned individual structural units yield a considerable SERS enhancement. This enables each single unit to function as an isolated sensor. Each of the formed structures can be effectively tuned and tailored to provide high SERS enhancement, while arising from different HEHD morphologies. The HEHD fabrication of sub-micrometer architectures is straightforward and robust, providing an elegant route for high-throughput biological and chemical sensing. The superior detection properties and the ability to fabricate SERS substrates on the miniaturized scale, will facilitate the development of advanced and novel opto-fluidic devices, such as portable detection systems, and will offer numerous applications in biomedical diagnostics, forensics, ecological warfare and homeland security.

Keywords: hierarchical electrohydrodynamic patterning, medical diagnostics, point-of care devices, SERS

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Authors: Jaehyun Choi, Hyunjung Kim, Namho Kim

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Earthwork is one of the critical civil construction operations that require large-quantities of resources due to its intensive dependency upon construction equipment. Therefore, efficient construction equipment management can highly contribute to productivity improvements and cost savings. Earthwork operation utilizes various combinations of construction equipment in order to meet project requirements such as time and cost. Identification of site condition and construction methods should be performed in advance in order to develop a proper execution plan. The factors to be considered include capacity of equipment assigned, the method of construction, the size of the site, and the surrounding condition. In addition, optimal combination of various construction equipment should be selected. However, in real world practice, equipment utilization plan is performed based on experience and intuition of management. The researchers evaluated the efficiency of various alternatives of construction equipment combinations by utilizing the process simulation model, validated the model from a case study project, and presented a methodology to find optimized plan among alternatives.

Keywords: earthwork operation, construction equipment, process simulation, optimization

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Authors: C. Puangsawat, C. Limotai, P. Srikhachin

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Bio-psycho-social caring was required for promoting the quality of life of the patients with epilepsy (PWE), despite controlled seizures. Multifaceted issues emerge at the epilepsy clinic. Unpredicted seizures, antiepileptic drug compliance problems/adverse effects, psychiatric, and social problems are all needed to be explored and managed. The Nursing Service System (NSS) at the tertiary epilepsy clinic (TEC) was consequently developed for improving the clinical care for PWE. Case manager concept was integrated as the framework guiding the processes and strategies used for developing the NSS as well as the roles of the multidisciplinary team at the clinic. This study aimed to report the outcomes of the developed NSS integrated case manager concept. The processes of our developed NSS program included 1) screening for patient’s problems using questionnaire prior to seeing epileptologists i.e., assessing the patient’s risk to develop acute seizures at the clinic, issues related to medication use, and uncovered psychiatric and social problems; and 2) assigning the patients at risk to be evaluated and managed by appropriate team. Nurses specializing in epilepsy in coordination with the multidisciplinary team implemented the NSS to promote coordinated work among the team which consists of epileptologists, nurses, pharmacists, psychologists, and social workers. Determination of the role of each person and their responsibilities along with joint care plan were clearly established. One year after implementation, the rate of acute seizure occurrence at the clinic was decreased, and satisfactory feedback from the patients was received. In order to achieve an optimal goal to promote self-management behaviors in PWE, continuing the NSS and systematic assessment of its effectiveness is required.

Keywords: case manager concept, nursing service system, patients with epilepsy, quality of life

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Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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