Search results for: drug delivery to the brain

Authors: Signe Svensson, Remy Rey, Anna-Lisa Osvalder, Henrik Artman, Lars Nordström

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The electric power system is undergoing significant changes. Thereby, the operation and control are becoming partly modified, more multifaceted and automated, and thereby supplementary operator skills might be required. This paper discusses developing operational challenges in future power system control rooms, posed by the evolving landscape of sustainable power systems, driven in turn by the shift towards electrification and renewable energy sources. A literature review followed by interviews and a comparison to other related domains with similar characteristics, a descriptive analysis was performed from a human factors perspective. Analysis is meant to identify trends, relationships, and challenges. A power control domain taxonomy includes a temporal domain (planning and real-time operation) and three operational domains within the power system (generation, switching and balancing). Within each operational domain, there are different control actions, either in the planning stage or in the real-time operation, that affect the overall operation of the power system. In addition to the temporal dimension, the control domains are divided in space between a multitude of different actors distributed across many different locations. A control room is a central location where different types of information are monitored and controlled, alarms are responded to, and deviations are handled by the control room operators. The operators’ competencies, teamwork skills, team shift patterns as well as control system designs are all important factors in ensuring efficient and safe electricity grid management. As the power system evolves with sustainable energy technologies, challenges are found. Questions are raised regarding whether the operators’ tacit knowledge, experience and operation skills of today are sufficient to make constructive decisions to solve modified and new control tasks, especially during disturbed operations or abnormalities. Which new skills need to be developed in planning and real-time operation to provide efficient generation and delivery of energy through the system? How should the user interfaces be developed to assist operators in processing the increasing amount of information? Are some skills at risk of being lost when the systems change? How should the physical environment and collaborations between different stakeholders within and outside the control room develop to support operator control? To conclude, the system change will provide many benefits related to electrification and renewable energy sources, but it is important to address the operators’ challenges with increasing complexity. The control tasks will be modified, and additional operator skills are needed to perform efficient and safe operations. Also, the whole human-technology-organization system needs to be considered, including the physical environment, the technical aids and the information systems, the operators’ physical and mental well-being, as well as the social and organizational systems.

Keywords: operator, process control, energy system, sustainability, future control room, skill

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Authors: Poojan Gharat, Haridas Pal, Sharmistha Dutta Choudhury

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Tuning photophysical properties of guest dyes through host-guest interactions involving macrocyclic hosts are the attractive research areas since past few decades, as these changes can directly be implemented in chemical sensing, molecular recognition, fluorescence imaging and dye laser applications. Excited state intramolecular proton transfer (ESIPT) is an intramolecular prototautomerization process display by some specific dyes. The process is quite amenable to tunability by the presence of different macrocyclic hosts. The present study explores the interesting effect of p-sulfonatocalix[n]arene (SCXn) and cyclodextrin (CD) hosts on the excited-state prototautomeric equilibrium of Chrysazine (CZ), a model antitumour drug. CZ exists exclusively in its normal form (N) in the ground state. However, in the excited state, the excited N* form undergoes ESIPT along with its pre-existing intramolecular hydrogen bonds, giving the excited state prototautomer (T*). Accordingly, CZ shows a single absorption band due to N form, but two emission bands due to N* and T* forms. Facile prototautomerization of CZ is considerably inhibited when the dye gets bound to SCXn hosts. However, in spite of lower binding affinity, the inhibition is more profound with SCX6 host as compared to SCX4 host. For CD-CZ system, while prototautomerization process is hindered by the presence of β-CD, it remains unaffected in the presence of γCD. Reduction in the prototautomerization process of CZ by SCXn and βCD hosts is unusual, because T* form is less dipolar in nature than the N*, hence binding of CZ within relatively hydrophobic hosts cavities should have enhanced the prototautomerization process. At the same time, considering the similar chemical nature of two CD hosts, their effect on prototautomerization process of CZ would have also been similar. The atypical effects on the prototautomerization process of CZ by the studied hosts are suggested to arise due to the partial inclusion or external binding of CZ with the hosts. As a result, there is a strong possibility of intermolecular H-bonding interaction between CZ dye and the functional groups present at the portals of SCXn and βCD hosts. Formation of these intermolecular H-bonds effectively causes the pre-existing intramolecular H-bonding network within CZ molecule to become weak, and this consequently reduces the prototautomerization process for the dye. Our results suggest that rather than the binding affinity between the dye and host, it is the orientation of CZ in the case of SCXn-CZ complexes and the binding stoichiometry in the case of CD-CZ complexes that play the predominant role in influencing the prototautomeric equilibrium of the dye CZ. In the case of SCXn-CZ complexes, the results obtained through experimental findings are well supported by quantum chemical calculations. Similarly for CD-CZ systems, binding stoichiometries obtained through geometry optimization studies on the complexes between CZ and CD hosts correlate nicely with the experimental results. Formation of βCD-CZ complexes with 1:1 stoichiometry while formation of γCD-CZ complexes with 1:1, 1:2 and 2:2 stoichiometries are revealed from geometry optimization studies and these results are in good accordance with the observed effects by the βCD and γCD hosts on the ESIPT process of CZ dye.

Keywords: intermolecular proton transfer, macrocyclic hosts, quantum chemical studies, photophysical studies

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Authors: Valentina V. Goftman, Vladislav A. Pankratov, Alexey V. Markin, Tangi Aubert, Zeger Hens, Sarah De Saeger, Irina Yu. Goryacheva

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The most important requirements for biochemical applicability of quantum dots (QDs) are: 1) the surface cap should render intact or improved optical properties; 2) mono-dispersion and good stability in aqueous phase in a wide range of pH and ionic strength values; 3) presence of functional groups, available for bioconjugation; 4) minimal impact from the environment on the QDs’ properties and, vice versa, minimal influence of the QDs’ components on the environment; and 5) stability against chemical/biochemical/physical influence. The latter is especially important for in vitro and in vivo applications. For example, some physical intracellular delivery strategies (e.g., electroporation) imply a rapid high-voltage electric field impulse in order to temporarily generate hydrophilic pores in the cell plasma membrane, necessary for the passive transportation of QDs into the cell. In this regard, it is interesting to investigate how different capping layers, which can provide high stability and sufficient fluorescent properties of QDs in a water solution, behave under these abnormal conditions. In this contribution, hydrophobic core-shell CdSe/CdS/CdZnS/ZnS QDs (λem=600 nm), produced by means of the Successive Ion Layer Adsorption and Reaction (SILAR) technique, were transferred to a water solution using two of the most commonly used methods: (i) encapsulation in an amphiphilic brush polymer based on poly(maleic anhydride-alt-1-octadecene) (PMAO) modified with polyethylene glycol (PEG) chains and (ii) silica covering. Polymer encapsulation preserves the initial ligands on the QDs’ surface owing to the hydrophobic attraction between the hydrophobic groups of the amphiphilic molecules and the surface hydrophobic groups of the QDs. This covering process allows maintaining the initial fluorescent properties, but it leads to a considerable increase of the QDs’ size. However, covering with a silica shell, by means of the reverse microemulsion method, allows maintaining both size and fluorescent properties of the initial QDs. The obtained water solutions of polymer covered and silica-coated QDs in three different concentrations were exposed to a low-voltage electric field for a short time and the fluorescent properties were investigated. It is shown that the PMAO-PEG polymer acquires some additional charges in the presence of the electric field, which causes repulsion between the polymer and the QDs’ surface. This process destroys the homogeneity of the whole amphiphilic shell and it dramatically decreases the fluorescent properties (dropping to 10% from its initial value) because of the direct contact of the QDs with the strongly oxidative environment (water). In contrast, a silica shell possesses dielectric properties which allow retaining 90% of its initial fluorescence intensity, even after a longer electric impact. Thus, silica shells are clearly a preferable covering for bio-application of QDs, because – besides the high uniform morphology, controlled size and biocompatibility – it allows protecting QDs from oxidation, even under the influence of an electric field.

Keywords: electric field, polymer coating, quantum dots, silica covering, stability

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Authors: Celine Shi Ying Lee, Jong Jian Lee

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Background: Infectious keratitis is one of the leading causes of blindness worldwide. Prompt treatment with effective medication will control the infection early, preventing corneal scarring and visual loss. fluoroquinolones ophthalmic medication is used because of its broad-spectrum properties, potency, good intraocular penetration, and low toxicity. The study aims to evaluate the treatment outcome of corneal ulcers using Levofloxacin 1.5% ophthalmic solution (LVFX) with adjuvant oral ciprofloxacin when indicated and apply this treatment strategy in primary health care as first-line treatment. Methods: Patients with infective corneal ulcer treated in an eye center were recruited. Inclusion criteria includes Corneal infection consistent with bacterial keratitis, single or multiple small corneal ulcers. Treatment regime: LVFX hourly for the first 2 days, 2 hourly from the 3rd day, and 3 hourly on the 5th day of review. Adjuvant oral ciprofloxacin 500mg BD was administered for 5 days if there were multiple corneal ulcers or when the location of the cornea ulcer was central or paracentral. Results: 47 subjects were recruited. There were 16 (34%) males and 31 (66%) females. 40 subjects (85%) were contact lens (CL) related to corneal ulcer, and 7 subjects (15%) were non-contact lens related. 42 subjects (89%) presented with one ulcer, of which 20 of them (48%) needed adjuvant therapy. 5 subjects presented with 2 or 3 ulcers, of which 3 needed adjuvant therapy. A total of 23 subjects (49%) was given adjuvant therapy (oral ciprofloxacin 500mg BD for 5 days).21 of them (91%) were CL related. All subjects recovered fully, and the average duration of treatment was 3.7 days, with 49% of the subjects resolved on the 3rd day, 38% on the 5thday of and 13% on the 7thday. All subjects showed symptoms of relief of pain, light-sensitivity, and redness on the 3rd day with full visual recovery post-treatment. No adverse drug reactions were recorded. Conclusion: Our treatment regime demonstrated good clinical outcome as first-line treatment for corneal ulcers. A corneal ulcer is a common eye condition in Singapore, mainly due to CL wear. Pseudomonas aeruginosa is the most frequent and potentially sight-threatening pathogen involved in CL related corneal ulcer. Coagulase-negative Staphylococci, Staphylococcus aureus, and Streptococcus Pneumoniae were seen in non-CL users. All these bacteria exhibit good sensitivity rates to ciprofloxacin and levofloxacin. It is therefore logical in our study to use LVFX Eyedrops and adjuvant ciprofloxacin oral antibiotics when indicated as first line treatment for most corneal ulcers. Our study of patients, both CL related and non-CL related, have shown good clinical response and full recovery using the above treatment strategy. There was also a full restoration of visual acuity in all the patients. Eye-trained primary Healthcare practitioners can consider adopting this treatment strategy as first line treatment in patients with corneal ulcers. This is relevant during the COVID pandemic, where hospitals are overwhelmed with patients and in regions with limited access to specialist eye care. This strategy would enable early treatment with better clinical outcome.

Keywords: corneal ulcer, levofloxacin hydrate, treatment strategy, ciprofloxacin

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Authors: Lilian Nantume Wampande

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Group-based strategies in the delivery of HIV care have opened up new avenues not only for meaningful participation for HIV positive people but also platforms for deconstruction and reconstruction of knowledge about living with the virus. Yet the contributions of such strategies among patients who live in high risk areas are still not explored. This case study research assessed the impact of HIV support networks on sexual health outcomes of HIV positive out-of-school adolescents residing in fishing islands of Kalangala in Uganda. The study population was out-of-school adolescents living with HIV and their sexual partners (n=269), members of their households (n=80) and their health service providers (n=15). Data were collected via structured interviews, observations and focus group discussions between August 2016 and March 2017. Data was then analyzed inductively to extract key themes related to the approaches and outcomes of the groups’ activities. The study findings indicate that support groups unite HIV positive adolescents in a bid for social renegotiation to achieve change but individual constraints surpass the groups’ intentions. Some adolescents for example reported increased fear which led to failure to cope, sexual violence, self-harm and denial of status as a result of the high expectations placed on them as members of the support groups. Further investigations around this phenomenon show that HIV networks play a monotonous role as information sources for HIV positive out-of-school adolescents which limit their creativity to seek information elsewhere. Results still indicate that HIV adolescent groups recognize the complexity of long-term treatment and stay in care leading to improved immunity for the majority yet; there is still scattered evidence about how effective they are among adolescents at different phases in the disease trajectory. Nevertheless, the primary focus of developing adolescent self-efficacy and coping skills significantly address a range of disclosure difficulties and supports autonomy. Moreover, the peer techniques utilized in addition to the almost homogeneous group characteristics accelerates positive confidence, hope and belongingness. Adolescent HIV-support groups therefore have the capacity to both improve and/or worsen sexual health outcomes for a young adolescent who is out-of-school. Communication interventions that seek to increase awareness about ‘self’ should therefore be emphasized more than just fostering collective action. Such interventions should be sensitive to context and gender. In addition, facilitative support supervision done by close and trusted health care providers, most preferably Village Health Teams (who are often community elected volunteers) would help to follow-up, mentor, encourage and advise this young adolescent in matters involving sexuality and health outcomes. HIV/AIDS prevention programs have extended their efforts beyond individual focus to those that foster collective action, but programs should rekindle interpersonal level strategies to address the complexity of individual behavior.

Keywords: adolescent, HIV, support groups, Uganda

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Authors: Jovina Concepcion Bachynski, Lenora Duhn, Idevania G. Costa, Pilar Camargo-Plazas

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Kidney failure is a life-limiting condition for which treatment, such as dialysis (hemodialysis and peritoneal dialysis), can exact a tremendously high physical and psychosocial symptom burden. Kidney failure can be severe enough to require a palliative approach to care. The term supportive care can be used in lieu of palliative care to avoid the misunderstanding that palliative care is synonymous with end-of-life or hospice care. Kidney supportive care, encompassing advance care planning, is an approach to care that improves the quality of life for people receiving dialysis through early identification and treatment of symptoms throughout the disease trajectory. Advanced care planning involves ongoing conversations about the values, goals, and preferences for future care between individuals and their healthcare teams. Kidney supportive care is underutilized and often initiated late in this population. There is evidence to indicate nurses are not providing the necessary elements of supportive kidney care. Dialysis nurses’ delay or lack of engagement in supportive care until close to the end of life may result in people dying without receiving optimal palliative care services. Using Charmaz’s constructivist grounded theory, the purpose of this doctoral study is to develop a substantive theory that explains the process of engagement in supportive care by nurses working in dialysis settings in Canada. Through initial purposeful and subsequent theoretical sampling, 23 nurses with current or recent work experience in outpatient hemodialysis, home hemodialysis, and peritoneal dialysis settings drawn from across Canada were recruited to participate in two intensive interviews using the Zoom© teleconferencing platform. Concurrent data collection and data analysis, constant comparative analysis of initial and focused codes until the attainment of theoretical saturation, and memo-writing, as well as researcher reflexivity, have been undertaken to aid the emergence of concepts, categories, and, ultimately, the constructed theory. At the time of abstract submission, data analysis is currently at the second level of coding (i.e., focused coding stage) of the research study. Preliminary categories include: (a) focusing on biomedical care; (b) multi-dimensional challenges to having the conversation; (c) connecting and setting boundaries with patients; (d) difficulty articulating kidney-supportive care; and (e) unwittingly practising kidney-supportive care. For the conference, the resulting theory will be presented. Nurses working in dialysis are well-positioned to ensure the delivery of quality kidney-supportive care. This study will help to determine the process and the factors enabling and impeding nurse engagement in supportive care in dialysis to effect change for normalizing advance care planning conversations in the clinical setting. This improved practice will have substantive beneficial implications for the many individuals living with kidney failure and their supporting loved ones.

Keywords: dialysis, kidney failure, nursing, supportive care

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Authors: Jong H. Kim, Kathleen L. Chan, Luisa W. Cheng

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Control of fungal pathogens, such as foodborne mycotoxin producers, is problematic as effective antimycotic agents are often very limited. Mycotoxin contamination significantly interferes with the safe production of foods or crops worldwide. Moreover, expansion of fungal resistance to commercial drugs or fungicides is a global human health concern. Therefore, there is a persistent need to enhance the efficacy of commercial antimycotic agents or to develop new intervention strategies. Disruption of the cellular antioxidant system should be an effective method for pathogen control. Such disruption can be achieved with safe, redox-active compounds. Natural phenolic derivatives are potent redox cyclers that inhibit fungal growth through destabilization of the cellular antioxidant system. The goal of this study is to identify novel, redox-active compounds that disrupt the fungal antioxidant system. The identified compounds could also function as sensitizing agents to conventional antimycotics (i.e., chemosensitization) to improve antifungal efficacy. Various benzo derivatives were tested against fungal pathogens. Gene deletion mutants of the yeast Saccharomyces cerevisiae were used as model systems for identifying molecular targets of benzo analogs. The efficacy of identified compounds as potent antifungal agents or as chemosensitizing agents to commercial drugs or fungicides was examined with methods outlined by the Clinical Laboratory Standards Institute or the European Committee on Antimicrobial Susceptibility Testing. Selected benzo derivatives possessed potent antifungal or antimycotoxigenic activity. Molecular analyses by using S. cerevisiae mutants indicated antifungal activity of benzo derivatives was through disruption of cellular antioxidant or cell wall integrity system. Certain benzo analogs screened overcame tolerance of Aspergillus signaling mutants, namely mitogen-activated protein kinase mutants, to fludioxonil fungicide. Synergistic antifungal chemosensitization greatly lowered minimum inhibitory or fungicidal concentrations of test compounds, including inhibitors of mitochondrial respiration. Of note, salicylaldehyde is a potent antimycotic volatile that has some practical application as a fumigant. Altogether, benzo derivatives targeting cellular antioxidant system of fungi (along with cell wall integrity system) effectively suppress fungal growth. Candidate compounds possess the antifungal, antimycotoxigenic or chemosensitizing capacity to augment the efficacy of commercial antifungals. Therefore, chemogenetic approaches can lead to the development of novel antifungal intervention strategies, which enhance the efficacy of established microbe intervention practices and overcome drug/fungicide resistance. Chemosensitization further reduces costs and alleviates negative side effects associated with current antifungal treatments.

Keywords: antifungals, antioxidant system, benzo derivatives, chemosensitization

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Authors: I. Brezeanu, J. Mackrill, A. Cajo, C. Mogollon

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Modern Slavery is a serious crime, where often the victims are unable to leave their situation of exploitation, being controlled by threats, punishment, violence, coercion, and deception. In the UK, this term encompasses both Slavery and Human Trafficking. The number of potential victims who were referred to the National Referral Mechanism (NRM) increased exponentially in the past decade, passing from fewer than 700 potential victims referred in 2010 to more than 12.000 in 2021. Our study aims to explore how the concept of Trauma-Informed Care (TIC) approach can be adopted by services working with survivors of Modern Slavery and Trafficking (MST). Notably, in this paper, we will elaborate on how the complex needs of survivors are related to their traumatic experiences and what are the necessary steps and resources for implementing a Modern Slavery Trauma-Informed model. While there are relatively few services in the UK that have a deep understanding of the survivors’ and practitioners’ views of how trauma impacts their daily life, there is a strong need for developing services that are organised and delivered in ways that prevent retraumatisation and enable trauma survivors to engage safely with the right professionals at the right time, promoting healing through positive relationships. Such models, known as Trauma-Informed Approaches (TIAs), are seen as crucial to the empowerment of survivors, yet they remain a marginal implementation model by governments, law enforcement, judiciary, or care providers, who are frequently survivors’ first point of contact in the recovery process. In order to understand better how to provide best practice and to adopt the concept, this study is based on a multi-disciplinary approach, encompassing both theoretical perspectives and co-production. By combining qualitative and quantitative research and comparing different analysis of applied examples of TIC in the US and the UK, we gained important insights about the prevention and impact of trauma on survivors’ life. The articulation between more general expertise on Trauma-Informed Care developed by other institutions operating in the field, and the SJOG delivery, based on the Salvation Army’s Modern Slavery Victim Care and Coordination Contract (MSVCC) and the Care Quality Commission regulations, allowed to identify on one side what are the complex needs of survivors derived from their traumatic experiences, and on the other side, how could MST services prevent retraumatisation. Additional, two in-depth interviews with survivors, who receive support from one of our services at Olallo House in London, and a survey shared among all colleagues working with MST services completed the findings of the research with their personal experience and knowledge. Ultimately, we developed an evidence-based Trauma-Informed Care Pathway that aims to improve the wellbeing of survivors and to support them to live a meaningful life. The establishedpathway delivers three main outcomes belonging to the social determinants of health criteria – health and wellbeing, purpose and relationship, and covers key themes of the context of trauma, needs of individuals, and service support.

Keywords: trauma-informed care, modern slavery, human trafficking, trauma, retraumatisation

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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: Anupalli Roja Rani, Pavithra Dasari

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Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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Authors: Ana Paula S. Horodenski, Priscila Pelegrini, Salli Baggenstoss

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The brewing industry with artisanal concepts seeks to serve a specific market, with diversified production that has been gaining ground in the national environment, also in the Amazon region. This growth is due to the more demanding consumer, with a diversified taste that wants to try new types of beer, enjoying products with new aromas, flavors, as a differential of what is so widely spread through the big industrial brands. Thus, through qualitative research methods, the study aimed to investigate how is the process of managing the production of a craft brewery in a city in the northern State of Mato Grosso (BRAZIL), providing knowledge of production processes and strategies in the industry. With the efficient use of resources, it is possible to obtain the necessary quality and provide better performance and differentiation of the company, besides analyzing the best management model. The research is descriptive with a qualitative approach through a case study. For the data collection, a semi-structured interview was elaborated, composed of the areas: microbrewery characterization, artisan beer production process, and the company supply chain management. Also, production processes were observed during technical visits. With the study, it was verified that the artisan brewery researched develops preventive maintenance strategies with the inputs, machines, and equipment, so that the quality of the product and the production process are achieved. It was observed that the distance from the supplying centers makes the management of processes and the supply chain be carried out with a longer planning time so that the delivery of the final product is satisfactory. The production process of the brewery is composed of machines and equipment that allows the control and quality of the product, which the manager states that for the productive capacity of the industry and its consumer market, the available equipment meets the demand. This study also contributes to highlight one of the challenges for the development of small breweries in front of the market giants, that is, the legislation, which fits the microbreweries as producers of alcoholic beverages. This makes the micro and small business segment to be taxed as a major, who has advantages in purchasing large batches of raw materials and tax incentives because they are large employers and tax pickers. It was possible to observe that the supply chain management system relies on spreadsheets and notes that are done manually, which could be simplified with a computer program to streamline procedures and reduce risks and failures of the manual process. In relation to the control of waste and effluents affected by the industry is outsourced and meets the needs. Finally, the results showed that the industry uses preventive maintenance as a productive strategy, which allows better conditions for the production and quality of artisanal beer. The quality is directly related to the satisfaction of the final consumer, being prized and performed throughout the production process, with the selection of better inputs, the effectiveness of the production processes and the relationship with the commercial partners.

Keywords: artisanal brewery, production management, production processes, supply chain

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Authors: Xincheng Jiang, Yanyan An, Yaoyao Huang, Wei Ding, Manli Sun, Hong Li, Huaili Zheng

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The residual antibiotics in the environment will pose a threat to the environment and human health. Thus, efficient removal and rapid detection of norfloxacin (NOR) in wastewater is very important. The main sources of NOR pollution are the agricultural, pharmaceutical industry and hospital wastewater. The total consumption of NOR in China can reach 5440 tons per year. It is found that neither animals nor humans can totally absorb and metabolize NOR, resulting in the excretion of NOR into the environment. Therefore, residual NOR has been detected in water bodies. The hazards of NOR in wastewater lie in three aspects: (1) the removal capacity of the wastewater treatment plant for NOR is limited (it is reported that the average removal efficiency of NOR in the wastewater treatment plant is only 68%); (2) NOR entering the environment will lead to the emergence of drug-resistant strains; (3) NOR is toxic to many aquatic species. At present, the removal and detection technologies of NOR are applied separately, which leads to a cumbersome operation process. The development of simultaneous adsorption-flocculation removal and FTIR detection of pollutants has three advantages: (1) Adsorption-flocculation technology promotes the detection technology (the enrichment effect on the material surface improves the detection ability); (2) The integration of adsorption-flocculation technology and detection technology reduces the material cost and makes the operation easier; (3) FTIR detection technology endows the water treatment agent with the ability of molecular recognition and semi-quantitative detection for pollutants. Thus, it is of great significance to develop a smart water treatment material with high removal capacity and detection ability for pollutants. This study explored the feasibility of combining NOR removal method with the semi-quantitative detection method. A magnetic Cu-Ni-S/Ni foam was synthesized by in-situ loading Cu-Ni-S nanostructures on the surface of Ni foam. The novelty of this material is the combination of adsorption-flocculation technology and semi-quantitative detection technology. Batch experiments showed that Cu-Ni-S/Ni foam has a high removal rate of NOR (96.92%), wide pH adaptability (pH=4.0-10.0) and strong ion interference resistance (0.1-100 mmol/L). According to the Langmuir fitting model, the removal capacity can reach 417.4 mg/g at 25 °C, which is much higher than that of other water treatment agents reported in most studies. Characterization analysis indicated that the main removal mechanisms are surface complexation, cation bridging, electrostatic attraction, precipitation and flocculation. Transmission FTIR detection experiments showed that NOR on Cu-Ni-S/Ni foam has easily recognizable FTIR fingerprints; the intensity of characteristic peaks roughly reflects the concentration information to some extent. This semi-quantitative detection method has a wide linear range (5-100 mg/L) and a low limit of detection (4.6 mg/L). These results show that Cu-Ni-S/Ni foam has excellent removal performance and semi-quantitative detection ability of NOR molecules. This paper provides a new idea for designing and preparing multi-functional water treatment materials to achieve simultaneous removal and semi-quantitative detection of organic pollutants in water.

Keywords: adsorption-flocculation, antibiotics detection, Cu-Ni-S/Ni foam, norfloxacin

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Authors: Zahra Mohajer, Afsaneh Soltani

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Doping is a major issue in competitive sports and is favored by vast groups of athletes. The feeling of being higher-ranking than others and gaining fame has caused many athletes to misuse drugs. The definition of doping is to use prohibited substances and/or methods that help physical or mental performances or both. Doping counts as the illegal use of chemical substances or drugs, excessive amounts of physiological substances to increase the performance at or out of competition or even the use of inappropriate medications to treat an injury to gain the ability to participate in a competition. The International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have forbidden these substances to ensure fair and equal competition and also the health of the competitors. As of 2004 WADA has published an international list of illegal substances used for doping, which is updated annually. In the process of the Genome Project scientists have gained the ability to treat numerous diseases by gene therapy, which may result in bodily performance increase and therefore a potential opportunity to misuse by some athletes. Gene doping is defined as the non-therapeutic direct and indirect genetic modifications using genetic materials that can improve the performances in sports events. Biosynthetic drugs are a form of indirect genetic engineering. The method can be performed in three ways such as injecting the DNA directly into the muscle, inserting the genetically engineered cells, or transferring the DNA using a virus as a vector. Erythropoietin is a hormone majorly released by the kidney and in small amounts by the liver. Its function is to stimulate the erythropoiesis and therefore the more production of red blood cells (RBC) which causes an increase in Hemoglobin (Hb). During this process, the oxygen delivery to muscles will increase, which will improve athletic performance and postpone exhaustion. There are ways to increase the oxygen transferred to muscles such as blood transfusion, stimulating the production of red blood cells by using Erythropoietin (EPO), and also using allosteric effectors of Hemoglobin. EPO can either be injected as a protein or can be inserted into the cells as the gene which encodes EPO. Adeno-associated viruses have been employed to deliver the EPO gene to the cells. Employing the genes that naturally exist in the human body such as the EPO gene can reduce the risk of detecting gene doping. The first research about blood doping was conducted in 1947. The study has shown that an increase in hematocrit (HCT) up to 55% following homologous transfusion makes it more unchallenging for the body to perform the exercise at the altitude. Thereafter athletes’ attraction to blood infusion escalated. Also, a study has demonstrated that by reinfusing their own blood 4 weeks after being drawn, three men have shown a rise in Hb level which improved the oxygen uptake, and a delay in exhaustion. The list of performance-enhancing drugs is published by WADA annually and includes the following drugs: anabolic agents, hormones, Beta-2 agonists, Beta-blockers, Diuretics, Stimulants, narcotics, cannabinoids, and corticosteroids.

Keywords: doping, PEDs, sports, WADA

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Authors: Aritra Das, Tanmay Mahapatra, Prabir Maharana, Sridhar Srikantiah

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In the absence of adequate well-equipped neonatal-care facilities serving rural Bihar, India, the practice of essential home-based newborn-care remains critically important for reduction of neonatal and infant mortality, especially among pre-term and small-for-gestational-age (Low-birth-weight) newborns. To improve the child health parameters in Bihar, ‘Very-Low-Birth-Weight (vLBW) Tracking’ intervention is being conducted by CARE India, since 2015, targeting public facility-delivered newborns weighing ≤2000g at birth, to improve their identification and provision of immediate post-natal care. To assess the effectiveness of the intervention, 200 public health facilities were randomly selected from all functional public-sector delivery points in Bihar and various outcomes were tracked among the neonates born there. Thus far, one pre-intervention (Feb-Apr’2015-born neonates) and three post-intervention (for Sep-Oct’2015, Sep-Oct’2016 and Sep-Oct’2017-born children) follow-up studies were conducted. In each round, interviews were conducted with the mothers/caregivers of successfully-tracked children to understand outcome, service-coverage and care-seeking during the neonatal period. Data from 171 matched facilities common across all rounds were analyzed using SAS-9.4. Identification of neonates with birth-weight ≤ 2000g improved from 2% at baseline to 3.3%-4% during post-intervention. All indicators pertaining to post-natal home-visits by frontline-workers (FLWs) improved. Significant improvements between baseline and post-intervention rounds were also noted regarding mothers being informed about ‘weak’ child – at the facility (R1 = 25 to R4 = 50%) and at home by FLW (R1 = 19%, to R4 = 30%). Practice of ‘Kangaroo-Mother-Care (KMC)’– an important component of essential newborn care – showed significant improvement in postintervention period compared to baseline in both facility (R1 = 15% to R4 = 31%) and home (R1 = 10% to R4=29%). Increasing trend was noted regarding detection and birth weight-recording of the extremely low-birth-weight newborns (< 1500 g) showed an increasing trend. Moreover, there was a downward trend in mortality across rounds, in each birth-weight strata (< 1500g, 1500-1799g and >= 1800g). After adjustment for the differential distribution of birth-weights, mortality was found to decline significantly from R1 (22.11%) to R4 (11.87%). Significantly declining trend was also observed for both early and late neonatal mortality and morbidities. Multiple regression analysis identified - birth during immediate post-intervention phase as well as that during the maintenance phase, birth weight > 1500g, children of low-parity mothers, receiving visit from FLW in the first week and/or receiving advice on extra care from FLW as predictors of survival during neonatal period among vLBW newborns. vLBW tracking was found to be a successful and sustainable intervention and has already been handed over to the Government.

Keywords: weak newborn tracking, very low birth weight babies, newborn care, community response

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Authors: Syue-Wen Lin

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Objective: This article explores the nursing experience of an 84-year-old male lung cancer patient who underwent a thoracoscopic right lower lobectomy and treatment. The patient has multiple medical histories, including hypertension and diabetes. The nursing process involved cancer treatment, postoperative pain management, as well as wound care and healing. Methods: The nursing period is from February 10 to February 17, 2024. During the nursing process, pain management strategies are implemented, including morphine drugs and non-drug methods, and music therapy, essential oil massage, and extended reception time are used to make patients feel physically and mentally comfortable so as to reduce postoperative pain and encourage active participation in rehabilitation. Strict sterile wound dressing procedures and advanced wound care techniques are used to promote wound healing and prevent infection. Due to septic shock, dialysis is used to relieve worsening symptoms. Taking into account the patient's cancer status, the nursing team provides comprehensive cancer care based on the patient's physical and psychological needs. Given the complexity of the patient's condition, including advanced cancer, palliative care is also incorporated throughout the care process to relieve discomfort and provide psychological support. Results: Through comprehensive health assessment, the nursing team fully understood the patient's condition and developed a personalized care plan based on the patient's condition. The interprofessional critical care team provides respiratory therapy and lung expansion exercises to reduce muscle loss while addressing the patient's psychological status, pain management, and vital sign stabilization needs, resulting in a comprehensive approach to care. Lung expansion exercises and the use of a high-frequency chest wall oscillation vest successfully improved sputum drainage and facilitated weaning from mechanical ventilation. In addition, helping patients stabilize their vital signs and the integration of cancer care, pain management, wound care and palliative care helps the patient be fully supported throughout the recovery process, ultimately improving his quality of life. Conclusion: Lung cancer and septic shock present significant challenges to patients, and the nursing team not only provides critical care but also addresses the unique needs of patients through comprehensive infection control, cancer care, pain management, wound care, and palliative care interventions. These measures effectively improve patients' quality of life, promote recovery, and provide compassionate palliative care for terminally ill patients. Nursing staff work closely with family members to develop a comprehensive care plan to ensure that patients receive high-quality medical care as well as psychological support and a comfortable recovery environment.

Keywords: septic shock, lung cancer, palliative care, nursing experience

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Authors: Samantha Jeffries, Chontit Chuenurah

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Thailand incarcerates the largest number of women and has the highest female incarceration rate in South East Asia. Since the 1990s, there has been a substantial increase in the number, rate and proportion of women imprisoned. Thailand places a high priority on the gender specific contexts out of which offending arises and the different needs of women in the criminal justice system. This is manifested in work undertaken to guide the development of the United Nations Rules for the Treatment of Women Prisoners and Non-Custodial Measures for Women Offenders (the Bangkok Rules); adopted by the United Nations General Assembly in 2010. The Bangkok Rules make a strong statement about Thailand’s recognition of and commitment to the fair and equitable treatment of women throughout their contact with the criminal justice system including at sentencing and in prison. This makes the comparatively high use of imprisonment for women in Thailand particularly concerning and raises questions about the relationship between gender, crime and criminal justice. While there is an extensive body of research in Western jurisdictions exploring women’s pathways to prison, there is a relative dearth of methodologically robust research examining the possible gendered circumstances leading to imprisonment in Thailand. In this presentation, we will report preliminary findings from a qualitative study of women’s pathways to prison in Thailand. Our research aims were to ascertain: 1) the type, frequency, and context of criminal behavior that led to women’s incarceration, 2) women’s experiences of the criminal justice system, 3) the broader life experiences and circumstances that led women to prison in Thailand. In-depth life history interviews (n=77) were utilized to gain a comprehensive understanding of women’s journeys into prison. The interview schedule was open-ended consisting of prisoner responses to broad discussion topics. This approach provided women with the opportunity to describe significant experiences in their lives, to bring together distinct chronologies of events, and to analyze links between their varied life experiences, offending, and incarceration. Analyses showed that women’s journey’s to prison take one of eight pathways which tentatively labelled as follows, the: 1) harmed and harming pathway, 2) domestic/family violence victimization pathway, 3) drug connected pathway, 4) street woman pathway, 5) economically motivated pathway, 6) jealousy anger and/or revenge pathway, 7) naivety pathway, 8) unjust and/or corrupted criminal justice pathway. Each will be fully discussed during the presentation. This research is significant because it is the first in-depth methodologically robust exploration of women’s journeys to prison in Thailand and one of a few studies to explore gendered pathways outside of western contexts. Understanding women’s pathways into Thailand’s prisons is crucial to the development of effective planning, policy and program responses not only while women are in prison but also post-release. To best meet women’s needs in prison and effectively support their reintegration, we must have a comprehensive understanding of who these women are, what offenses they commit, the reasons that trigger their confrontations with the criminal justice system and the impact of the criminal justice system on them.

Keywords: pathways, prison, women, Thailand

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Authors: Margaret Boone Rappaport, Christopher J. Corbally

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The ancient ape ancestral population from which living great ape and human species evolved had demographic features affecting their evolution. The population was large, had great genetic variability, and natural selection was effective at honing adaptations. The emerging populations of chimpanzees and humans were affected more by founder effects and genetic drift because they were smaller. Natural selection did not disappear, but it was not as strong. Consequences of the 'population crash' and the human effective population size are introduced briefly. The history of the ancient apes is written in the genomes of living humans and great apes. The expansion of the brain began before the human line emerged. Coalescence times for some genes are very old – up to several million years, long before Homo sapiens. The mismatch between gene trees and species trees highlights the anthropoid speciation processes, and gives the human genome history a fuzzy, probabilistic quality. However, it suggests traits that might form a foundation for capacities emerging later. A theoretical model is presented in which the genomes of early ape populations provide the substructure for the emergence of religious capacity later on the human line. The model does not search for religion, but its foundations. It suggests a course by which an evolutionary line that began with prosimians eventually produced a human species with biologically based religious capacity. The model of the sequential emergence of religious capacity relies on cognitive science, neuroscience, paleoneurology, primate field studies, cognitive archaeology, genomics, and population genetics. And, it emphasizes five trait types: (1) Documented, positive selection of sensory capabilities on the human line may have favored survival, but also eventually enriched human religious experience. (2) The bonobo model suggests a possible down-regulation of aggression and increase in tolerance while feeding, as well as paedomorphism – but, in a human species that remains cognitively sharp (unlike the bonobo). The two species emerged from the same ancient ape population, so it is logical to search for shared traits. (3) An up-regulation of emotional sensitivity and compassion seems to have occurred on the human line. This finds support in modern genetic studies. (4) The authors’ published model of morality's emergence in Homo erectus encompasses a cognitively based, decision-making capacity that was hypothetically overtaken, in part, by religious capacity. Together, they produced a strong, variable, biocultural capability to support human sociability. (5) The full flowering of human religious capacity came with the parietal expansion and smaller face (klinorhynchy) found only in Homo sapiens. Details from paleoneurology suggest the stage was set for human theologies. Larger parietal lobes allowed humans to imagine inner spaces, processes, and beings, and, with the frontal lobe, led to the first theologies composed of structured and integrated theories of the relationships between humans and the supernatural. The model leads to the evolution of a small population of African hominins that was ready to emerge with religious capacity when the species Homo sapiens evolved two hundred thousand years ago. By 50-60,000 years ago, when human ancestors left Africa, they were fully enabled.

Keywords: genetic drift, genomics, parietal expansion, religious capacity

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Authors: Lauren Dhugga, Meena Parameswaran, David Blundell, Abbas Khushnood

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Context: A multidisciplinary weekly safety briefing was implemented at the Paediatric Cardiothoracic Unit at the Freeman Hospital in Newcastle-upon-Tyne. It is a tertiary referral centre with a quarternary cardiac paediatric intensive care unit and provides complexed care including heart and lung transplants, mechanical support and advanced heart failure assessment. Aim: The aim of this briefing is to provide a structured platform of communication, in an effort to improve efficiency, safety, and patient care. Problem: The paediatric cardiothoracic unit is made up of a vast multidisciplinary team including doctors, intensivists, anaesthetists, surgeons, specialist nurses, echocardiogram technicians, physiotherapists, psychologists, dentists, and dietitians. It provides care for children with congenital and acquired cardiac disease and is one of only two units in the UK to offer paediatric heart transplant. The complexity of cases means that there can be many teams involved in providing care to each patient, and frequent movement of children between ward, high dependency, and intensive care areas. Currently, there is no structured forum for communicating important information across the department, for example, staffing shortages, prescribing errors and significant events. Strategy: An initial survey questioning the need for better communication found 90% of respondents agreed that they could think of an incident that had occurred due to ineffective communication, and 85% felt that incident could have been avoided had there been a better form of communication. Lastly, 80% of respondents felt that a weekly 60 second safety briefing would be beneficial to improve communication within our multidisciplinary team. Based on those promising results, a weekly 60 second safety briefing was implemented to be conducted on a Monday morning. The safety briefing covered four key areas (SAFE): staffing, awareness, fix and events. This was to highlight any staffing gaps, any incident reports to be learned from, any issues that required fixing and any events including teachings for the week ahead. The teams were encouraged to email suggestions or issues to be raised for the week or to approach in person with information to add. The safety briefing was implemented using change theory. Effect: The safety briefing has been trialled over 6 weeks and has received a good buy in from staff across specialties. The aim is to embed this safety briefing into a weekly meeting using the PDSA cycle. There will be a second survey in one month to assess the efficacy of the safety briefing and to continue to improve the delivery of information. The project will be presented at the next clinical governance briefing to attract wider feedback and input from across the trust. Lessons: The briefing displays promise as a tool to improve vigilance and communication in a busy multi-disciplinary unit. We have learned about how to implement quality improvement and about the culture of our hospital - how hierarchy influences change. We demonstrate how to implement change through a grassroots process, using a junior led briefing to improve the efficiency, safety, and communication in the workplace.

Keywords: briefing, communication, safety, team

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Authors: Kamelia Hamza

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Background: Proton pump inhibitors (PPIs) are the most prescribed drug classes for pediatric gastroesophageal reflux disease (GERD).Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux (GER), even in the absence of proved causal relationship. There is an impression of increase use of PPI's treatment for reflux in "clalit health services," the largest health organization in Israel. In the recent years, the medicine is given without restriction, it's not limited to pediatric gastroenterologists only, but pediatricians and family doctors. The objective of this study is to evaluate the hypothesis that exposure to PPIs during the first year of life is associated with an increased risk of developing late adverse diseases: pneumonia, asthma, AGE, IBD, celiac disease, allergic disorders, obesity, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders (ASD). Methods: The study is a retrospective case-control cohort study based on a computerized database of Clalit Health Services (CHS). It includes 9844 children born between 2002-2018 and reported to complain of at least one of the symptoms (reflux/ spitting up, irritability, feeding difficulties, colics). The study population included the study group (n=4922) of children exposed to PPIs at any time prior to the first year of life and a control group (n=4922) child not exposed to PPIs who were matched to each case of the study group on age, race, socioeconomic status, and year of birth. The prevalence of late complications/diseases in the study group was compared with the prevalence of late complications/diseases diagnosis between 2002-2020 in the control group. Odds ratios and 95% confidence intervals were calculated by using logistic regression models. Results: We found that compared to the control group, children exposed to PPIs in the first year of life had an increased risk of developing several late complications/ disorders: pneumonia, asthma, various allergies (urticaria, allergic rhinitis, or allergic conjunctivitis) OR, inhalant allergies, and food allergies. In addition, they showed an increased risk of being diagnosed with ADHD or ASD, but children exposed to PPIs in the first year of life had decrease the risk of obesity by 17% (OR 0.825, 95%CI 0.697-0.976). Conclusions: We found significant associations between the use of PPIs during the first year of life and subsequent development of late complications/diseases such as respiratory diseases, allergy diseases, ADHD, and ASD. More studies are needed to prove causality and determine the mechanism behind the effect of PPIs and the development of late complications.

Keywords: acid suppressing medications, proton pump inhibitors, histamine 2 blocker, late complications, gastroesophageal reflux, gastroesophageal reflux disease, acute gastroenteritis, community acquired pneumonia, asthma, allergic diseases, obesity, inflammatory bowel diseases, ulcerative colitis, crohn disease, attention deficit hyperactivity disorders, autism spectrum disorders

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Authors: Egemen Sert, Leila Hedayatifar, Rachel A. Rigg, Amir Akhavan, Olha Buchel, Dominic Elias Saadi, Aabir Abubaker Kar, Alfredo J. Morales, Yaneer Bar-Yam

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The complexity of providing timely and cost-effective distribution of finished goods from industrial facilities to customers makes effective operational coordination difficult, yet effectiveness is crucial for maintaining customer service levels and sustaining a business. Logistics planning becomes increasingly complex with growing numbers of customers, varied geographical locations, the uncertainty of future orders, and sometimes extreme competitive pressure to reduce inventory costs. Linear optimization methods become cumbersome or intractable due to a large number of variables and nonlinear dependencies involved. Here we develop a complex systems approach to optimizing logistics networks based upon dimensional reduction methods and apply our approach to a case study of a manufacturing company. In order to characterize the complexity in customer behavior, we define a “customer space” in which individual customer behavior is described by only the two most relevant dimensions: the distance to production facilities over current transportation routes and the customer's demand frequency. These dimensions provide essential insight into the domain of effective strategies for customers; direct and indirect strategies. In the direct strategy, goods are sent to the customer directly from a production facility using box or bulk trucks. In the indirect strategy, in advance of an order by the customer, goods are shipped to an external warehouse near a customer using trains and then "last-mile" shipped by trucks when orders are placed. Each strategy applies to an area of the customer space with an indeterminate boundary between them. Specific company policies determine the location of the boundary generally. We then identify the optimal delivery strategy for each customer by constructing a detailed model of costs of transportation and temporary storage in a set of specified external warehouses. Customer spaces help give an aggregate view of customer behaviors and characteristics. They allow policymakers to compare customers and develop strategies based on the aggregate behavior of the system as a whole. In addition to optimization over existing facilities, using customer logistics and the k-means algorithm, we propose additional warehouse locations. We apply these methods to a medium-sized American manufacturing company with a particular logistics network, consisting of multiple production facilities, external warehouses, and customers along with three types of shipment methods (box truck, bulk truck and train). For the case study, our method forecasts 10.5% savings on yearly transportation costs and an additional 4.6% savings with three new warehouses.

Keywords: logistics network optimization, direct and indirect strategies, K-means algorithm, dimensional reduction

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Authors: Fatima Meirkhankyzy Shaizadina, Alua Oralovna Omarova, Praskovya Mikhailovna Britskaya, Nessipkul Oryntayevna Alysheva

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In recent years in the Republic of Kazakhstan there have been registered outbreaks of measles among the population. The objective of work was the analysis of outbreak of measles in 2014 among the population of North-Kazakhstan region of the Republic of Kazakhstan. For the analysis of the measles outbreak descriptive and analytical research, techniques were used and threshold levels of morbidity were calculated. The increase of incidence was noted from March to July. The peak was registered in May and made 9.0 per 100000 population. High rates were registered in April – 5.7 per 100000 population, and in June and July they made 5.7 and 3.1 respectively. Duration of the period of increase made 5 months. The analysis of monthly incidence of measles revealed spring and summer seasonality. Across the territory it was established that 69.2% of cases were registered in the city, 29.1% in rural areas and 1.7% of cases were brought in from other regions of Kazakhstan. The registered cases and threshold values of measles during the outbreak revealed that from 12 to 24 week, and also during the 40th week the cases exceeding the threshold levels are registered. Thus, for example, for the analyzed 1 week the number of the revealed patients made 4, which exceeds the calculated threshold value (3) by 33.3%. The data exceeding the threshold values confirm the emergence of a disease outbreak or the beginning of epidemic rise in morbidity. Epidemic rise in incidence of the population of North-Kazakhstan region was observed throughout 2014. The risk group includes 0-4 year-old children, who made 22.7%, 15-19 year-olds – 25.6%, 20-24 year-olds – 20.9%. The analysis of measles cases registration by gender revealed that women are registered 1.1 times more often than men. The ratio of women to men made 1:0.87. In social and professional groups often ill are unorganized children – 23.3% and students – 19.8%. Studying clinical manifestations of measles in the hospitalized patients, the typical beginning of a disease with expressed intoxication symptoms – weakness, sickliness was established. In individual cases expressed intoxication symptoms, hemorrhagic and dyspeptic syndromes, complications in the form of overlay of a secondary bacterial infection, which defined high severity of the illness, were registered both in adults and in children. The average duration of stay of patients in the hospital made 6.9 days. The average duration of time between date of getting the disease and date of delivery of health care made 3.6 days. Thus, the analysis of monthly incidence of measles revealed spring and summer seasonality, the peak of which was registered in May. Urban dwellers are ill more often (69.2%), while in rural areas people are ill more rarely (29.1%). Throughout 2014 an epidemic rise in incidence of the population of North-Kazakhstan region was observed. Risk group includes: children under 4 – 22.7%, 15-19 year-olds – 25.6%, 20-24 year-olds – 20.9%. The ratio of women and men made 1:0.87. The typical beginning of a disease in all hospitalized with the expressed intoxication symptoms – weakness, sickliness was established.

Keywords: epidemiological analysis, measles, morbidity, outbreak

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Authors: Rashed Shah, Jeanne Koepsell, Dixmer Rivera, Eric Swedberg, David Marsh

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Success of primary health care goals of health promotion and disease prevention may well be determined by community based health workers’ overall job satisfaction. It is also important to understand the ways community health workers perceive their jobs and the importance they give to the various factors influencing their job satisfaction, which is critical before making a decision for task-shifting and for expanding their scope of work. Although brigadistas are unpaid volunteers, they are formally recognized and receive support and supervision from the Ministry of Health in Nicaragua. Brigadistas are responsible for classifying and diagnosing illnesses, administering treatment, counseling mothers and care givers within the community, encouraging referral in case of serious illness and making follow-up visits at home. Some brigadistas provide more technically advanced services, including treatment for pneumonia, diarrhea, malaria and tuberculosis and/or distribution of contraceptives. Expanding brigadistas’ duties could threaten their heretofore ‘job satisfaction’. This study primarily aims to report on job satisfaction of brigadistas in Nicaragua before expanding the scope of their work by adding more responsibilities. The study was guided by the following research questions: 1) What aspects of their job made the brigadistas satisfied or dissatisfied? 2) What is the job satisfaction level of brigadistas in Nicaragua? This cross-sectional study was conducted during March – July 2014, to assess brigadistas’ job satisfaction, prior to deciding on inclusion of care for sick newborns and young infants (<2 months of age) to brigadistas’ existing service package of community case management for children of 2-59 months of age. Following stratified random sampling strategy, 15 brigadistas were randomly selected from each of the following four strata: [(1) females under 25 years of age, (2) females over 30 years of age, (3) males under 25 years of age, and (4) males over 30 years of age. Out of 45 completed in-person interview with eligible and available brigadistas, 20 (44.4%) were with female and 25 (55.6%) were with male respondents; the mean age (±sd) was found as 32.0 (±3.2) years. About 53% (24/45) brigadista mentioned “Training” as the most helpful for performing their job. Another 31% (14/45) mentioned that “feeling of doing good, supporting community, women and children” was helpful to perform their job well. When asked about difficulty, about 35.5% (16/45) brigadistas mentioned about “Lack of time” due to their responsibilities in family, farm, other work places, study and such time constraint made their job performance difficult. Measured on a 0-5 scale, estimated average job satisfaction was 4.2. Current trends in task-shifting and integrated program delivery require community health workers (like the brigadistas) to deliver several essential services, including maternal, newborn and child health, and family planning, and thereby increasing their responsibilities. Given the reported level of job satisfaction among brigadistas (4.2 out of 5), and the mentioned difficulty in performing their current job (as ‘Lack of Time’) in this study results, the policy makers and program managers in MOH should be cautious enough before making a decision to expand current scope of work for brigadistas in Nicaragua.

Keywords: Brigadisata, job satisfaction, Nicaragua, task-shifting

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Authors: Jessica Peart, Sarim Al Zubaidy

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This paper examines the main dialogic and reformative aspects that have constituted the developing implementation of an English language module in a common pre-sessional program in Oman, the General Foundation Program (GFP), at the new Military Technological College (MTC), in Oman’s capital, muscat. The MTC is the first of its kind in the country to merge military with academic training and has been running programs since September 2013 over five trimesters to date, receiving external validation and accreditation from the University of Portsmouth (UoP), UK. From this starting point, We will provide context on the parameters that necessitated delivery of this common but specially tailored pre-sessional program at the MTC and outline in detail how the English module with integrated key study skills and personal tutoring support was initially conceived before operations commenced and cooperation between all stakeholders took practical shape. This enquiry traces how stakeholders from students to faculty, college boards and collaborative university partners have considered and redefined the in part static and dynamic boundaries of their larger and smaller scale stakes. With regard to the widely held recognition that pre-sessional students require training in transferable study skills in order to succeed at university, we will chart the subsequent and ongoing adjustments made to the generic, pastoral and integrated elements of that program. Driving this concerted effort has been at base the need for a GFP concerned with three criteria for incoming MTC students cadets, namely to develop candidate’s rounded capacity for intellectual, technical and physical skill as both students and cadets, to generate linguistic proficiency and discerning use of appropriate language registers and to allow personal and collective time for adjustment to a multilayered, brand new environment, while also working within a regulated timeline for academic progression to the MTC diploma or degree levels. The English Department teaching staff’s facilitation of the initial program’s methodologies and timeframe for the GFP English module has garnered a keen and diverse sense of the holistic student cadet experience, which a range of alterations to the program demonstrate. These include alterations to the class types and overall program duration as well as greater multiplicity of exposure within learning environments. In surveying the impact of these composite maneuvers and challenges within a proactive and evolving context of teaching and learning, it is finally demonstrated how student cadet levels of productivity and self-reliance on the one hand and retention issues on the other are being gainfully steered towards progression within a framework for inclusive reciprocal dialogue, gathering thereby civilian and military backgrounds toward uniquely united ends.

Keywords: English module transferable skills, faculty dialogue, governance structure, overarching regulatory agencies

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Authors: Jessica Raven Gates, Gemma Wilson-Menzfeld, Professor Alison Steven

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In 2019, the Primary Care system in the UK National Health Service (NHS) was subject to reform and restructuring. Primary Care Networks (PCNs) were established, which aligned with a trend towards integrated care both within the NHS and internationally. The introduction of PCNs brought groups of GP practices in a locality together, to operate as a network, build on existing services and collaborate at a larger scale. PCNs were expected to bring a range of benefits to patients and address some of the workforce pressures in the NHS, through an expanded and collaborative workforce. The early establishment of PCNs was disrupted by the emerging COVID-19 pandemic. This study, set in the context of the pandemic, aimed to explore experiences of the PCN workforce, and their perceptions of the establishment of PCNs. Specific objectives focussed on examining factors perceived as enabling or hindering the success of a PCN, the impact on day-to-day work, the approach to implementing change, and the influence of the COVID-19 pandemic upon PCN development. This study is part of a three-phase PhD project that utilized qualitative approaches and was underpinned by social constructionist philosophy. Phase 1: a systematic narrative review explored the provision of preventative healthcare services in UK primary settings and examined facilitators and barriers to delivery as experienced by the workforce. Phase 2: informed by the findings of phase 1, semi-structured interviews were conducted with fifteen participants (PCN workforce). Phase 3: follow-up interviews were conducted with original participants to examine any changes to their experiences and perceptions of PCNs. Three main themes span across phases 2 and 3 and were generated through a Framework Analysis approach: 1) working together at scale, 2) network infrastructure, and 3) PCN leadership. Findings suggest that through efforts to work together at scale and collaborate as a network, participants have broadly accepted the concept of PCNs. However, the workforce has been hampered by system design and system complexity. Operating against such barriers has led to a negative psychological impact on some PCN leaders and others in the PCN workforce. While the pandemic undeniably increased pressure on healthcare systems around the world, it also acted as a disruptor, offering a glimpse into how collaboration in primary care can work well. Through the integration of findings from all phases, a new theoretical model has been developed, which conceptualises the findings from this Ph.D. study and demonstrates how the workforce has experienced change associated with the establishment of PCNs. The model includes a contextual component of the COVID-19 pandemic and has been informed by concepts from Complex Adaptive Systems theory. This model is the original contribution to knowledge of the PhD project, alongside recommendations for practice, policy and future research. This study is significant in the realm of health services research, and while the setting for this study is the UK NHS, the findings will be of interest to an international audience as the research provides insight into how the healthcare workforce may experience imposed policy and service changes.

Keywords: health services research, qualitative research, NHS workforce, primary care

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Authors: A. Sgobba, C. Meskell

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The feasibility of on-site electricity production from solar and wind and the resulting load management for a specific manufacturing plant in Ireland are assessed. The industry sector accounts directly and indirectly for a high percentage of electricity consumption and global greenhouse gas emissions; therefore, it will play a key role in emission reduction and control. Manufacturing plants, in particular, are often located in non-residential areas since they require open spaces for production machinery, parking facilities for the employees, appropriate routes for supply and delivery, special connections to the national grid and other environmental impacts. Since they have larger spaces compared to commercial sites in urban areas, they represent an appropriate case study for evaluating the technical and economic viability of energy system integration with low power density technologies, such as solar and wind, for on-site electricity generation. The available open space surrounding the analysed manufacturing plant can be efficiently used to produce a discrete quantity of energy, instantaneously and locally consumed. Therefore, transmission and distribution losses can be reduced. The usage of storage is not required due to the high and almost constant electricity consumption profile. The energy load of the plant is identified through the analysis of gas and electricity consumption, both internally monitored and reported on the bills. These data are not often recorded and available to third parties since manufacturing companies usually keep track only of the overall energy expenditures. The solar potential is modelled for a period of 21 years based on global horizontal irradiation data; the hourly direct and diffuse radiation and the energy produced by the system at the optimum pitch angle are calculated. The model is validated using PVWatts and SAM tools. Wind speed data are available for the same period within one-hour step at a height of 10m. Since the hub of a typical wind turbine reaches a higher altitude, complementary data for a different location at 50m have been compared, and a model for the estimate of wind speed at the required height in the right location is defined. Weibull Statistical Distribution is used to evaluate the wind energy potential of the site. The results show that solar and wind energy are, as expected, generally decoupled. Based on the real case study, the percentage of load covered every hour by on-site generation (Level of Autonomy LA) and the resulting electricity bought from the grid (Expected Energy Not Supplied EENS) are calculated. The economic viability of the project is assessed through Net Present Value, and the influence the main technical and economic parameters have on NPV is presented. Since the results show that the analysed renewable sources can not provide enough electricity, the integration with a cogeneration technology is studied. Finally, the benefit to energy system integration of wind, solar and a cogeneration technology is evaluated and discussed.

Keywords: demand, energy system integration, load, manufacturing, national grid, renewable energy sources

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Authors: Collen Tebogo Masilo, Erik Schmikl

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The demand for the DataMiner product by customers has presented a great challenge for the vendor in Skyline Communications in deploying its limited resources in the form of human resources, financial resources, and office space, to achieve high organisational performance in all its international operations. The rapid growth of the organisation has been unable to efficiently support its existing customers across the globe, and provide services to new customers, due to the limited number of approximately one hundred employees in its employ. The combined descriptive and explanatory case study research methods were selected as research design, making use of a survey questionnaire which was distributed to a sample of 100 respondents. A sample return of 89 respondents was achieved. The sampling method employed was non-probability sampling, using the convenient sampling method. Frequency analysis and correlation between the subscales (the four themes) were used for statistical analysis to interpret the data. The investigation was conducted into mechanisms that can be deployed to balance the high demand for products and the limited production capacity of the company’s Belgian operations across four aspects: demand management strategies, capacity management strategies, communication methods that can be used to align a sales management department, and reward systems in use to improve employee performance. The conclusions derived from the theme ‘demand management strategies’ are that the company is fully aware of the future market demand for its products. However, there seems to be no evidence that there is proper demand forecasting conducted within the organisation. The conclusions derived from the theme 'capacity management strategies' are that employees always have a lot of work to complete during office hours, and, also, employees seem to need help from colleagues with urgent tasks. This indicates that employees often work on unplanned tasks and multiple projects. Conclusions derived from the theme 'communication methods used to align sales management department with operations' are that communication is not good throughout the organisation. This means that information often stays with management, and does not reach non-management employees. This also means that there is a lack of smooth synergy as expected and a lack of good communication between the sales department and the projects office. This has a direct impact on the delivery of projects to customers by the operations department. The conclusions derived from the theme ‘employee reward systems’ are that employees are motivated, and feel that they add value in their current functions. There are currently no measures in place to identify unhappy employees, and there are also no proper reward systems in place which are linked to a performance management system. The research has made a contribution to the body of research by exploring the impact of the four sub-variables and their interaction on the challenges of organisational productivity, in particular where an organisation experiences a capacity problem during its growth stage during tough economic conditions. Recommendations were made which, if implemented by management, could further enhance the organisation’s sustained competitive operations.

Keywords: high demand for products, high organisational performance, limited production capacity, limited resources

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Authors: Erickson Bernardo, Caridad Pineda

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The project Adolescent Reproductive Health Information and Services (ARHIS) is a nine-month pilot project which intends to bridge the existing gap between reproductive health information and services, particularly with regard to family planning and HIV, among adolescent boys and girls aged 10-19 years in the 2nd Congressional District of Quezon City, in the Philippines. It aims to increase adolescents' and young people's awareness about their reproductive health concerns and at the same time make a wide range of reproductive health (RH) services accessible and available to them. A number of methodologies were utilized in the implementation of the project. At the onset, a baseline survey was conducted by community mobilizers to gather a situational analysis of adolescents' and young people's issues and concerns. The results of this survey were then presented in a multi-stakeholders' meeting to gather community support and foster their involvement. Further, interactive learning sessions (ILS) on a variety of reproductive health topics, among young people, parents and community leaders based on the results of the baseline survey was conducted. With regard to reproductive health service provision, both facility-based delivery and conduct of outreach activities were employed. In the span of nine months, the project was able to yield the following results: • A total of 521 adolescents and youth (AY) were reached by ILS on puberty, responsible relationships, teenage pregnancy, family planning, as well as HIV & AIDS. • A total of 218 parents and community leaders were informed of AY RH-related issues and concerns. • More than 350 AYs availed of a wide range of FP services including pills – both combined oral and progestin-only, and progestin-only injectables and implants. • More than 380 AYs availed of condoms as means of STI and HIV prevention. A noble initiative of the project is the utilization of a "condom distributor", a youth leader who has been educated about STI and HIV prevention as well as correct condom use, as the focal point for condom access in the community. • A total of 25 young people, parents, and community leaders were identified as ARHIS champions who have been instrumental in the achievement of project deliverables through their dedication and commitment to support the project. The concept of adolescent sexual and reproductive health (ASRH) remains to be a major challenge in the Philippine context. This is due to the fact that majority of Filipinos are still not keen on discussing issues and concerns related to ASRH, albeit the alarming number of teenage pregnancies and the rapid increase of HIV cases among 15- 24 year olds. In addition, Republic Act 10354 or the Responsible Parenthood and Reproductive Health Act of 2012, requires minor adolescents to present a written parental consent prior to accessing RH services. However, with the involvement and support of parents and key community stakeholders, these barriers may be addressed. The project has demonstrated how adolescents and young people yearn for reproductive health information and services.

Keywords: adolescent sexual reproductive health, barriers to access, reproductive health information and services, teenage pregnancies

Procedia PDF Downloads 177

Authors: Rafael Alexandre Dos Reis

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Research has shown a substantial increase in the participation of Conventionally Fuelled Vehicles (CFVs) in the urban transport modal split. The reasons for this unsustainable reality are multiple, from economic interventions to individual behaviour. The development and delivery of positive incentives for the adoption of more environmental-friendly modes of transport is an emerging strategy to help in tackling the problem of excessive use of conventionally fuelled vehicles. The efficiency of this approach, like other information-based schemes, can benefit from the knowledge of their potential impacts in theoretical constructs of multiple behaviour change theories. The goal of this research is to critically analyse theories of behaviour that are relevant to transport research and the impacts of positive incentives on the theoretical determinants of behaviour, strengthening the current body of evidence about the benefits of this approach. The main method to investigate this will involve a literature review on two main topics: the current theories of behaviour that have empirical support in transport research and the past or ongoing positive incentives programs that had an impact on car use reduction. The reviewed programs of positive incentives were the following: The TravelSmart®; Spitsmijden®; Incentives for Singapore Commuters® (INSINC); COMMUTEGREENER®; MOVESMARTER®; STREETLIFE®; SUPERHUB®; SUNSET® and the EMPOWER® project. The theories analysed were the heory of Planned Behaviour (TPB); The Norm Activation Theory (NAM); Social Learning Theory (SLT); The Theory of Interpersonal Behaviour (TIB); The Goal-Setting Theory (GST) and The Value-Belief-Norm Theory (VBN). After the revisions of the theoretical constructs of each of the theories and their influence on car use, it can be concluded that positive incentives schemes impact on behaviour change in the following manners: -Changing individual’s attitudes through informational incentives; -Increasing feelings of moral obligations to reduce the use of CFVs; -Increase the perceived social pressure to engage in more sustainable mobility behaviours through the use of comparison mechanisms in social media, for example; -Increase the perceived control of behaviour through informational incentives and training incentives; -Increasing personal norms with reinforcing information; -Providing tools for self-monitoring and self-evaluation; -Providing real experiences in alternative modes to the car; -Making the observation of others’ car use reduction possible; -Informing about consequences of behaviour and emphasizing the individual’s responsibility with society and the environment; -Increasing the perception of the consequences of car use to an individual’s valued objects; -Increasing the perceived ability to reduce threats to environment; -Help establishing goals to reduce car use; - iving personalized feedback on the goal; -Increase feelings of commitment to the goal; -Reducing the perceived complexity of the use of alternatives to the car. It is notable that the emerging technique of delivering positive incentives are systematically connected to causal determinants of travel behaviour. The preliminary results of the reviewed programs evidence how positive incentives might strengthen these determinants and help in the process of behaviour change.

Keywords: positive incentives, private car use reduction, sustainable behaviour, voluntary travel behaviour change

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Authors: Vladimir Berezin, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Aizhan Turmagambetova, Irina Zaitseva, Nadezhda Sokolova, Elmira Omirtaeva

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Introduction: Triterpene saponins of plant origin are one of the most promising candidates for elaboration of novel adjuvants. Due to the combination of immunostimulating activity and the capacity interact with amphipathic molecules with formation of highly immunogenic nanocomplexes, triterpene saponins could serve as a good adjuvant/delivery system for vaccine use. In the research presented adjuvants on the base of nanocomplexes contained triterpene saponins isolated from Glycyrrhiza glabra and Saponaria officinalis plants indigenous to Kazakhstan were elaborated for influenza vaccine use. Methods: Purified triterpene saponins 'Glabilox' and 'SO1' with low toxicity and high immunostimulatory activity were isolated from plants Glycyrrhiza glabra L. and Saponaria officinalis L. by high-performance liquid chromatography (HPLC) and identified using electrospray ionization mass spectrometry (ESI-MS). Influenza virus A/St-Petersburg/5/09 (H1N1) propagated in 9-days old chicken embryos was concentrated and purified by centrifugation in sucrose gradient. Nanocomplexes contained lipids, and triterpene saponins Glabilox or SO1 were prepared by dialysis technique. Immunostimulating activity of experimental vaccine preparations was studied in vaccination/challenge experiments in mice. Results: Humoral and cellular immune responses and protection against influenza virus infection were examined after single subcutaneous and intranasal immunization. Mice were immunized subunit influenza vaccine (HA+NA) or whole virus inactivated influenza vaccine in doses 3.0/5.0/10.0 µg antigen/animal mixed with adjuvant in dose 15.0 µg/animal. Sera were taken 14-21 days following single immunization and mice challenged by A/St-Petersburg/5/09 influenza virus in dose 100 EID₅₀. Study of experimental influenza vaccine preparations in animal immunization experiments has shown that subcutaneous and intranasal immunization with subunit influenza vaccine mixed with nanocomplexes contained Glabilox or SO1 saponins stimulated high levels of humoral immune response (IgM, IgA, IgG1, IgG2a, and IgG2b antibody) and cellular immune response (IL-2, IL-4, IL-10, and IFN-γ cytokines) and resulted 80-90% protection against lethal influenza infection. Also, single intranasal and single subcutaneous immunization with whole virus inactivated influenza vaccine mixed with nanoparticulated adjuvants stimulated high levels of humoral and cellular immune responses and provided 100% protection against lethal influenza infection. Conclusion: The results of study have shown that nanocomplexes contained purified triterpene saponins Glabilox and SO1 isolated from plants indigenous to Kazakhstan can stimulate a broad spectrum of humoral and cellular immune responses and induce protection against lethal influenza infection. Both elaborated adjuvants are promising for incorporation to influenza vaccine intended for subcutaneous and intranasal routes of immunization.

Keywords: influenza vaccine, adjuvants, triterpene saponins, immunostimulating activity

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Authors: Anuj Tyagi, Balwinder Singh, Naveen Kumar B. T., Niraj K. Singh

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Characterization of diverse microbial communities in specific environment plays a crucial role in the better understanding of their functional relationship with the ecosystem. It is now well established that gut microbiome of fish is not the simple replication of microbiota of surrounding local habitat, and extensive species, dietary, physiological and metabolic variations in fishes may have a significant impact on its composition. Moreover, overuse of antibiotics in human, veterinary and aquaculture medicine has led to rapid emergence and propagation of antibiotic resistance genes (ARGs) in the aquatic environment. Microbial communities harboring specific ARGs not only get a preferential edge during selective antibiotic exposure but also possess the significant risk of ARGs transfer to other non-resistance bacteria within the confined environments. This phenomenon may lead to the emergence of habitat-specific microbial resistomes and subsequent emergence of virulent antibiotic-resistant pathogens with severe fish and consumer health consequences. In this study, gut microbiota of freshwater carp (Labeo rohita) was investigated by shotgun metagenomics to understand its taxonomic composition and functional capabilities. Metagenomic DNA, extracted from the fish gut, was subjected to sequencing on Illumina NextSeq to generate paired-end (PE) 2 x 150 bp sequencing reads. After the QC of raw sequencing data by Trimmomatic, taxonomic analysis by Kraken2 taxonomic sequence classification system revealed the presence of 36 phyla, 326 families and 985 genera in the fish gut microbiome. At phylum level, Proteobacteria accounted for more than three-fourths of total bacterial populations followed by Actinobacteria (14%) and Cyanobacteria (3%). Commonly used probiotic bacteria (Bacillus, Lactobacillus, Streptococcus, and Lactococcus) were found to be very less prevalent in fish gut. After sequencing data assembly by MEGAHIT v1.1.2 assembler and PROKKA automated analysis pipeline, pathway analysis revealed the presence of 1,608 Metacyc pathways in the fish gut microbiome. Biosynthesis pathways were found to be the most dominant (51%) followed by degradation (39%), energy-metabolism (4%) and fermentation (2%). Almost one-third (33%) of biosynthesis pathways were involved in the synthesis of secondary metabolites. Metabolic pathways for the biosynthesis of 35 antibiotic types were also present, and these accounted for 5% of overall metabolic pathways in the fish gut microbiome. Fifty-one different types of antibiotic resistance genes (ARGs) belonging to 15 antimicrobial resistance (AMR) gene families and conferring resistance against 24 antibiotic types were detected in fish gut. More than 90% ARGs in fish gut microbiome were against beta-lactams (penicillins, cephalosporins, penems, and monobactams). Resistance against tetracycline, macrolides, fluoroquinolones, and phenicols ranged from 0.7% to 1.3%. Some of the ARGs for multi-drug resistance were also found to be located on sequences of plasmid origin. The presence of pathogenic bacteria and ARGs on plasmid sequences suggested the potential risk due to horizontal gene transfer in the confined gut environment.

Keywords: antibiotic resistance, fish gut, metabolic pathways, microbial diversity

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