Optimization and characterization of laccase (LccH) produced by Hexagonia hirta MSF2 in solid-state fermentation using coir pith wastes (CPW).

The accumulation of coir pith waste, a byproduct of coconut husk processing, poses environmental and logistical challenges. An innovative and sustainable solution involves using coir pith as a substrate for solid-state fermentation (SSF). In SSF, coir pith can be converted into valuable products, such as enzymes, organic acids, and bioactive compounds. The present study aimed to evaluate laccase production by Hexagonia hirta MSF2 through SSF using the coir pith waste as substrate. Physico-chemical parameters like moisture, pH, temperature, C source, N source, and CuSO4 concentrations were pre-optimized, and optimized through RSM. Laccase activity of 1585.24 U g-1 of dry substrate was recorded by H. hirta MSF2 on coir pith containing 1 % C source, 0.5 % N source, 0.25 mM of CuSO4 concentration, moisture content of 75 % at pH 4.6 and temperature 28 °C. Subsequently, the enzyme extraction parameters including, extraction buffer, mode of extraction, and temperature were optimized. The molecular weight of laccase was 66 kDa as observed by SDS-PAGE and native-PAGE. The optimum activity of partially purified laccase was achieved at 40 °C, and pH 4.0. Increasing salt concentration and use of different inhibitors affected the laccase activity. Organic solvents like dimethyl sulphoxide (DMSO) and methanol, and metal ions like BaCl2, CaCl2, CuSO4, and MnCl2 stimulated the laccase activity. Hence, coir pith used in SSF offers a dual benefit of waste management and enzyme synthesis through an eco-friendly and cost-effective approach.

MSF Enhances Human Antimicrobial Peptide ß-Defensin (HBD2 and HBD3) Expression and Attenuates Inflammation via the NF-κB and p38 Signaling Pathways.

Both defensin and inflammation are part of the human innate immune system that responds rapidly to pathogens. The combination of defensins with pro- or anti-inflammatory effects can be a potential research direction for the treatment of infection by pathogens. This study aimed to identify whether MSF (Miracle Synergy material made using Filipendula glaberrima), a probiotic lysate of Filipendula glaberrima extracts fermented with Lactiplantibacillus plantarum K8, activates the expression of human ß-defensin (HBD2 and HBD3) to protect the host against pathogens and inhibit inflammation caused by S. aureus, in vitro with Western blot analysis, qRT-PCR and in vivo studies with a mouse model were used to evaluate the effects of MSF. The MSF treatment induced HBD2 and HBD3 expression via the p38 and NF-κB pathways. Furthermore, MSF treatment significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-8), also through p38 and NF-κB in S. aureus-induced inflammatory condition. MSF treatment remarkably reduced erythema in mice ears caused by the injection of S. aureus, while K8 lysate treatment did not initiate a strong recovery. Taken together, MSF induced the expression of HBD2 and HDB3 and activated anti-inflammatory activity more than the probiotic lysates of L. plantarum K8. These findings show that MSF is a potential defensin inducer and anti-inflammatory agent.

Septin9 DNA methylation as a promising biomarker for cervical cancer.

Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.Impact statementWhat is already known on this subject? The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction.What the results of this study add? Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg.What the implications are of these findings for clinical practice and/or further research? This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.

Multisource feedback in medical students' workplace learning in primary health care.

BACKGROUND: In medical students' workplace learning, feedback is important for effective learning regarding communication and clinical skills. The provision of multisource feedback (MSF) in clinical practice with focus on the patient's perspective is rarely addressed in the literature. The overall objective was to explore the experience of MSF in medical students' clinical learning in primary healthcare (PHC). METHODS: In the study, patients provided feedback by use of the Patient Feedback in Clinical Practice (PFCP) questionnaire. By use of adapted PFCP questionnaire versions peers and clinical supervisors provided feedback and students performed a self-evaluation. The MSF learning activity was evaluated using surveys (4-point Likert scale/open-ended questions), (students (n = 26), peers (n = 9) and clinical supervisors (n = 7)). Data were analysed using descriptive and qualitative content analysis. RESULTS: Results (mean 4-point Likert scale) from participants evaluation of the MSF learning activity visualises the value of feedback in terms of patient-centred communication (students 3.50, peers 2.44 and clinical supervisors 3.57), guidance for further training (students 3.14, peers 2.89 and clinical supervisors 3.00) and clarification of pedagogical assignment (students 3.14, peers 2.89 and clinical supervisors 3.00). Thematic analysis of participants' free-text answers in the evaluation surveys resulted in three themes: (1) applicability of the MSF, (2) MSF - collaborative learning process and (3) MSF as a facilitator in students' clinical skills development. The participants experienced that the written MSF provided multi-facetted perspectives, which contributed to students' and peers' clinical and communication learning. MSF experience also enhanced clinical supervisors' feedback regarding communication skills, targeting the supervisors' pedagogical assignment. CONCLUSION: Our findings indicate that MSF provided directly after a patient encounter, using the PFCP questionnaire as feedback provider, could be an adequate learning activity for medical students' workplace learning. The MSF, provided through the PFCP questionnaire, was experienced to neutralise and operationalise the provision of concrete feedback, facilitating peers' learning and clinical supervisors' tuition. The results visualise the importance of patients in MSF, as a valuable resource in students' workplace learning. Our study implies that this learning activity could be an applicable tool to facilitate learning and pedagogic development in clinical education in PHC.

Value Change, Value Conflict, and Policy Innovation: Understanding the Opposition to the Market-Based Economic Dispatch of Electricity Scheme in India Using the Multiple Streams Framework.

As policy innovation is essential for upscaling responsible innovation, understanding its relationship to value change(s) occurring or sought in sociotechnical systems is imperative. In this study, we ask: what are the different types of values in the policy process? And, how does value change influence policy innovation? We propose a disaggregation of values and value change based on a four-stream variant of the multiple streams framework (MSF), a conceptual lens increasingly used for explaining policy innovation in sociotechnical transitions. Specifically, we posit that the values that 'govern' problem framing, policy design, political decision making, and technological diffusion can evolve relatively independently, potentially leading to value conflict. We apply this framework to the ongoing case of the market-based economic dispatch of electricity (MBED) policy in the Indian energy transition using content analysis. We find that the MBED scheme-with its emphasis on efficiency (problem), economic principles (policy), low-cost dispatch (technology), and centralization (politics)-attempts value change in each stream. Each instance of value change is, however, widely contested, with the ensuing value conflicts resulting in significant opposition to this policy innovation. We conclude that a disaggregation of values based on the MSF can facilitate an analysis of value change and value conflict in sociotechnical transitions and lay the foundation for systematically studying the relationships among technological change, value change, and policy change.

A GP fellowship project looking at whether the multi-source feedback and the educational supervisor's report can be used to identify trainees at risk of difficulty.

As a Wessex General Practice (GP) fellow working within the annual review of competency progression (ARCP) team, we wanted to identify trainees at an early stage of GP training who might be at risk of difficulty during their training scheme. Early identification would allow more time for these trainees to access additional training and wider deanery support. This project aimed to identify retrospectively whether the multi-source feedback (MSF) and the educational supervisor's report (ESR) completed in the first year of speciality training (ST1) could be used to identify trainees at risk of needing additional time in training beyond the three-year training programme. For the purposes of this project, a trainee at risk of difficulty is one who received a developmental outcome 3 (OC 3) at their final ARCP in their last year of GP speciality training (ST3) where the desired outcome is an outcome 6 (OC 6). This fellowship project demonstrated it is possible to use the first MSF in GP training alongside the ESR before their ARCP in ST1, to identify a large proportion (88%) of trainees who may be at risk of difficulty further in their training.

Hepatitis C viraemic and seroprevalence and risk factors for positivity in Northwest Cambodia: a household cross-sectional serosurvey.

BACKGROUND: Despite a dramatic reduction in HCV drug costs and simplified models of care, many countries lack important information on prevalence and risk factors to structure effective HCV services. METHODS: A cross-sectional, multi-stage cluster survey of HCV seroprevalence in adults 18 years and above was conducted, with an oversampling of those 45 years and above. One hundred forty-seven clusters of 25 households were randomly selected in two sets (set 1=24 clusters ≥18; set 2=123 clusters, ≥45). A multi-variable analysis assessed risk factors for sero-positivity among participants ≥45. The study occurred in rural Moung Ruessei Health Operational District, Battambang Province, Western Cambodia. RESULTS: A total of 5098 individuals and 3616 households participated in the survey. The overall seroprevalence was 2.6% (CI95% 2.3-3.0) for those ≥18 years, 5.1% (CI95% 4.6-5.7) for adults ≥ 45 years, and 0.6% (CI95% 0.3-0.9) for adults 18-44. Viraemic prevalence was 1.9% (CI95% 1.6-2.1), 3.6% (CI95% 3.2-4.0), and 0.5% (CI95% 0.2-0.8), respectively. Men had higher prevalence than women: ≥18 years male seroprevalence was 3.0 (CI95% 2.5-3.5) versus 2.3 (CI95% 1.9-2.7) for women. Knowledge of HCV was poor: 64.7% of all respondents and 57.0% of seropositive participants reported never having heard of HCV. Risk factor characteristics for the population ≥45 years included: advancing age (p< 0.001), low education (higher than secondary school OR 0.7 [95% CI 0.6-0.8]), any dental or gum treatment (OR 1.6 [95% CI 1.3-1.8]), historical routine medical care (medical injection after 1990 OR 0.7 [95% CI 0.6-0.9]; surgery after 1990 OR 0.7 [95% CI0.5-0.9]), and historical blood donation or transfusion (blood donation after 1980 OR 0.4 [95% CI 0.2-0.8]); blood transfusion after 1990 OR 0.7 [95% CI 0.4-1.1]). CONCLUSIONS: This study provides the first large-scale general adult population prevalence data on HCV infection in Cambodia. The results confirm the link between high prevalence and age ≥45 years, lower socio-economic status and past routine medical interventions (particularly those received before 1990 and 1980). This survey suggests high HCV prevalence in certain populations in Cambodia and can be used to guide national and local HCV policy discussion.

Designing a system for performance appraisal: balancing physicians' accountability and professional development.

BACKGROUND: In many healthcare systems, physicians are accustomed to periodically participate in individual performance appraisals to guide their professional development. For the purpose of revalidation, or maintenance of certification, they need to demonstrate that they have engaged with the outcomes of these appraisals. The combination of taking ownership in professional development and meeting accountability requirements may cause undesirable interference of purposes. To support physicians in their professional development, new Dutch legislation requires that they discuss their performance data with a non-hierarchical (peer)coach and draft a personal development plan. In this study, we report on the design of this system for performance appraisal in a Dutch academic medical center. METHODS: Using a design-based research approach, a hospital-based research group had the lead in drafting and implementing a performance appraisal protocol, selecting a multisource feedback tool, co-developing and piloting a coaching approach, implementing a planning tool, recruiting peer coaches and facilitating their training and peer group debriefings. RESULTS: The system consisted of a two-hour peer-to-peer conversation based on the principles of appreciative inquiry and solution-focused coaching. Sessions were rated as highly motivating, development-oriented, concrete and valuable. Peer coaches were considered suitable, although occasionally physicians preferred a professional coach because of their expertise. The system honored both accountability and professional development purposes. By integrating the performance appraisal system with an already existing internal performance system, physicians were enabled to openly and safely discuss their professional development with a peer, while also being supported by their superior in their self-defined developmental goals. Although the peer-to-peer conversation was mandatory and participation in the process was documented, it was up to the physician whether or not to share its results with others, including their superior. CONCLUSIONS: In the context of mandatory revalidation, professional development can be supported when the appraisal process involves three characteristics: the appraisal process is appreciative and explores developmental opportunities; coaches are trustworthy and skilled; and the physician has control over the disclosure of the appraisal output. Although the peer-to-peer conversations were positively evaluated, the effects on physicians' professional development have yet to be investigated in longitudinal research designs.

Migration Stimulating Factor (MSF): Its Role in the Tumour Microenvironment.

Migration Stimulating Factor (MSF) is a 70 kDa truncated isoform of fibronectin (FN); its mRNA is generated from the FN gene by an unusual two-stage processing. Unlike full-length FN, MSF is not a matrix molecule but a soluble protein which displays cytokine-like activities not displayed by any other FN isoform due to steric hindrance. There are two isoforms of MSF; these are referred to as MSF+aa and MSF-aa, while the term MSF is used to include both.MSF was first identified as a motogen secreted by foetal and cancer-associated fibroblasts in tissue culture. It is also produced by sprouting (angiogenic) endothelial cells, tumour cells and activated macrophages. Keratinocytes and resting endothelial cells secrete inhibitors of MSF that have been identified as NGAL and IGFBP-7, respectively. MSF+aa and MSF-aa show distinct functionality in that only MSF+aa is inhibited by NGAL.MSF is present in 70-80% of all tumours examined, expressed by the tumour cells as well as by fibroblasts, endothelial cells and macrophages in the tumour microenvironment (TME). High MSF expression is associated with tumour progression and poor prognosis in all tumours examined, including breast carcinomas, non-small cell lung cancer (NSCLC), salivary gland tumours (SGT) and oral squamous cell carcinomas (OSCC). Epithelial and stromal MSF carry independent prognostic value. MSF is also expressed systemically in cancer patients, being detected in serum and produced by fibroblast from distal uninvolved skin. MSF-aa is the main isoform associated with cancer, whereas MSF+aa may be expressed by both normal and malignant tissues.The expression of MSF is not invariant; it may be switched on and off in a reversible manner, which requires precise interactions between soluble factors present in the TME and the extracellular matrix in contact with the cells. MSF expression in fibroblasts may be switched on by a transient exposure to several molecules, including TGFß1 and MSF itself, indicating an auto-inductive capacity.Acting by both paracrine and autocrine mechanisms, MSF stimulates cell migration/invasion, induces angiogenesis and cell differentiation and alters the matrix and cellular composition of the TME. MSF is also a survival factor for sprouting endothelial cells. IGD tri- and tetra-peptides mimic the motogenic and angiogenic activities of MSF, with both molecules inhibiting AKT activity and requiring αvß3 functionality. MSF is active at unprecedently low concentrations in a manner which is target cell specific. Thus, different bioactive motifs and extracellular matrix requirements apply to fibroblasts, endothelial cells and tumour cells. Unlike other motogenic and angiogenic factors, MSF does not affect cell proliferation but it stimulates tumour growth through its angiogenic effect and downstream mechanisms.The epithelial-stromal pattern of expression and range of bioactivities displayed puts MSF in the unique position of potentially promoting tumour progression from both the "seed" and the "soil" perspectives.

Anything to Stay Alive: The Challenges of a Campaign for an Experimental Drug.

Drug-resistant tuberculosis (TB) has a high mortality rate. Most medicines used to treat it are poorly tested and have terrible side effects. Activists have campaigned for patients with drug-resistant TB to have access to experimental drugs, particularly one called bedaquiline, before these have been approved by regulatory authorities such as the Food and Drug Administration (FDA) in the United States (US) and the Medicines Control Council (MCC) in South Africa. Some activists have also campaigned for bedaquiline to be approved by regulatory authorities before testing of the drug is completed. These campaigns raise ethical concerns about whether patients should be offered experimental, unapproved, medicines for the treatment of life-threatening illnesses, and if authorities should approve drugs for life-threatening illnesses when vital questions about safety and efficacy remain outstanding.

Ebola outbreak in rural West Africa: epidemiology, clinical features and outcomes.

OBJECTIVE: To describe Ebola cases in the district Ebola management centre of in Kailahun, a remote rural district of Sierra Leone, in terms of geographic origin, patient and hospitalisation characteristics, treatment outcomes and time from symptom onset to admission. METHODS: Data of all Ebola cases from June 23rd to October 5th 2014 were reviewed. Ebola was confirmed by reverse-transcriptase-polymerase-chain-reaction assay. RESULTS: Of 489 confirmed cases (51% male, median age 28 years), 166 (34%) originated outside Kailahun district. Twenty-eight (6%) were health workers: 2 doctors, 11 nurses, 2 laboratory technicians, 7 community health workers and 6 other cadres. More than 50% of patients had fever, headache, abdominal pain, diarrhoea/vomiting. An unusual feature was cough in 40%. Unexplained bleeding was reported in 5%. Outcomes for the 489 confirmed cases were 227 (47%) discharges, 259 (53%) deaths and 3 transfers. Case fatality in health workers (68%) was higher than other occupations (52%, P = 0.05). The median community infectivity time was 6.5 days for both general population and health workers (P = 0.4). CONCLUSIONS: One in three admitted cases originated outside Kailahun district due to limited national access to Ebola management centres - complicating contact tracing, safe burial and disinfection measures. The comparatively high case fatality among health workers requires attention. The community infectivity time needs to be reduced to prevent continued transmission.

Working on the front line.

On 23 March 2014, the World Health Organization confirmed an outbreak of Ebola virus disease in Guinea. By August 2014, a delayed international response resulted in an unprecedented humanitarian emergency occurring in Guinea, Liberia and Sierra Leone. In this outbreak, over 26,000 people have been infected with Ebola virus and more than 10,000 have died. Médecins Sans Frontières led the emergency response on the ground treating over 5,000 confirmed cases of Ebola. This article reflects on challenges faced working in an Ebola treatment centre and what future research may offer.

Humanitarian assistance and accountability: what are we really talking about?

BACKGROUND: In the past two decades, there has been a worldwide increase in the number of disasters, as well as the number of people affected, along with the number of foreign medical teams (FMTs) deployed to provide assistance. However, in the wake of the 2010 Haiti earthquake, multiple reports and anecdotes questioned the actual, positive contribution of such FMTs and even the intentions behind these aid efforts. This brought on a renewed interest in the humanitarian community towards accountability. Between 2000 and 2012, the number of "Quality and Accountability" initiatives and instruments more than tripled from 42 to 147. Yet, to date, there is no single accepted definition of accountability in the humanitarian context. AIM: The aim of this report was to explore and assess how accountability in the humanitarian context is used and/or defined in the literature. METHODS: The electronic database PubMed and a predefined list of grey literature comprising 46 organizations were searched for articles that discussed or provided a definition of accountability in the humanitarian context. The definitions found in these articles were analyzed qualitatively using a framework analysis method based on principles of grounded theory as well as using a summative content analysis method. RESULTS: A total of 85 articles were reviewed in-depth. Fifteen organizations had formal definitions of accountability or explained what it meant to them. Accountability was generally seen in two paradigms: as a "process" or as a "goal." A total of 16 different concepts were identified amongst the definitions. Accountability to aid recipients had four main themes: empowering aid recipients, being in an optimal position to do the greatest good, meeting expectations, and being liable. The concepts of "enforcement/enforceability" under the last theme of "being liable" received the least mention. CONCLUSION: The concept of accountability is defined poorly in many humanitarian organizations. Humanitarian providers often refer to different concepts when talking about accountability in general. The lack of a common understanding is contributed by the semantic and practical complexities of the term. The lack of emphasis on "enforcement/enforceability" is noteworthy. Other aspects of accountability, such as its "measurability" and by whom, similarly lack a common understanding and community-wide consensus. To what extent these vague definitions of accountability affect agencies' work in the field remains to be documented.

Research to policy and practice change: is capacity building in operational research delivering the goods?

OBJECTIVES: Between 2009 and 2012, eight operational research capacity building courses were completed in Paris (3), Luxembourg (1), India (1), Nepal (1), Kenya (1) and Fiji (1). Courses had strict milestones that were subsequently adopted by the Structured Operational Research and Training InitiaTive (SORT IT) of the World Health Organization. We report on the numbers of enrolled participants who successfully completed courses, the number of papers published and their reported effect on policy and/or practice. DESIGN: Retrospective cohort study including a survey. METHODS: Participant selection criteria ensured that only those proposing specific programme-related and relevant operational research questions were selected. Effects on policy and/or practice were assessed in a standardised manner by two independent reviewers. RESULTS: Of 93 enrolled participants from 31 countries (14 in Africa, 13 in Asia, two in Latin America and two in South Pacific), 83 (89%) completed their courses. A total of 96 papers were submitted to scientific journals of which 89 (93%) were published and 88 assessed for effect on policy and practice. There was a reported effect in 65 (74%) studies including changes to programme implementation (27), adaptation of monitoring tools (24) and changes to existing guidelines (20). CONCLUSION: Three quarters of published operational research studies from these structured courses had reported effects on policy and/or practice. It is important that this type of tracking becomes a standard component of operational research and research in general.

Migration-stimulating factor (MSF) is over-expressed in non-small cell lung cancer and promotes cell migration and invasion in A549 cells over-expressing MSF.

Migration-stimulating factor (MSF), an oncofetal truncated isoform of fibronectin, is a potent stimulator of cell invasion. However, its distribution and motogenic role in non-small cell lung cancer (NSCLC) have never been identified. In this study, real-time PCR and immunohistochemical staining (IHC) were performed to detect MSF mRNA and protein levels in tumor tissues and matched adjacent tumor-free tissues. Furthermore, to examine the effect of MSF on invasiveness, MSF was upregulated in A549 cells. The invasiveness and viability of A549 cells were then determined using a transwell migration assay and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assays, respectively. The expression level of MSF in NSCLC tissue was markedly higher than in matched adjacent tumor-free tissue. Additionally, the level of MSF protein expression in stage III and IV NSCLC samples was higher than in stage I and II NSCLC samples. More importantly, we also demonstrated that migration and invasion of A549 cells increased substantially after upregulating MSF, although proliferation remained unchanged. Meanwhile, we found no correlation between increasing motility and invasiveness of MSF-overexpressing cells and expression levels and activities of matrix metalloprotease MMP-2 and MMP-9. Our current study shows that MSF plays a role in migration and invasion of A549 cells and suggests that MSF may be a potential biomarker of NSCLC progression.

Needs-driven versus market-driven pharmaceutical innovation: the consortium for the development of a new medicine against malaria in Brazil.

The prevailing model for encouraging innovation based on patents and market-oriented raises at least two economic and ethical issues: it imposes barriers on individuals and developing countries governments' access to medicines by defining prices that do not match their income, and the unavailability of new or appropriate products to address the health problems of these populations. In the last decade, this scenario has undergone some changes due to the emergence of new actors, the contribution of aid resources, the introduction to the market of new products against neglected diseases, the development of new governmental healthcare policies and research programs, etc. One example of such initiatives is the Fixed-Dose Artesunate Combination Therapy (FACT) project consortium, which brought together institutions with different natures from both the North and the South, for the development of two antimalarial fixed-dose combinations recommended by the WHO - artesunate-amodiaquine (ASAQ) and artesunate-mefloquine (ASMQ). This paper proposes to describe and analyze the ASMQ consortium, which is the result of a new pharmaceutical development approach, based on a different paradigm - needs-driven instead of market-driven -, collaborative, with strategic participation of institutions from the South, funded by alternative resources (public and philanthropic). Thus, it represents an interesting object of study for bioethical debates on intellectual property and innovation, and its analysis is justified in light of the current debate on ways of stimulating needs-driven pharmaceutical innovation.

Challenges of a Circular Economy: The Example of Raw Recycled Tyre Steel Fibres Added to Concrete.

This research was conducted to analyse the possibility of using raw, untreated recycled tyre fibres as an effective concrete reinforcement according to circular economy principles. The aim of the article was also to develop a method for dispensing tire fibres on a real scale. Additional treatment and homogenisation of recycled steel fibres entail higher energy consumption, emissions of greenhouse gases, and increased costs. However, obtaining durable and safe concrete effectively reinforced with steel fibres is critical. Finding a balance between environmental friendliness and product durability is a circular economic challenge. Reference concrete with commercial steel fibres (15 kg/m3) and two concretes containing various quantities of non-treated, raw tyre recycled fibres (25 kg/m3 and 45 kg/m3) were industrially produced. Tests were carried out on the properties of the concrete mixture and hardened concrete, such as compressive strength, flexural strength, splitting strength, modulus of elasticity, residual flexural tensile strength, and fibre distribution in concrete. Tests revealed that increasing the amount of raw tyre fibres disturbs the structure and causes air entrainment and the formation of fibre clusters. Smaller quantities of raw tyre fibres turn out an effective concrete reinforcement. The use of non-treated tyre fibres as concrete reinforcement is possible but requires more stringent control of the concrete parameters. Implementation tests on an industrial scale are a novelty in this study, presenting an analysis of the possible dispensing of tyre fibres in a ready-mixed concrete production plant and testing the characteristics of manufactured concrete.

Prediction of the Bubble Growth Behavior by Means of the Time-, Temperature-, Pressure- and Blowing Agent Concentration-Dependent Transient Elongational Viscosity Function of Polymers.

Bubble growth processes are highly complex processes, which are not only dependent on the foaming process parameters (temperature, pressure and blowing agent concentration) but also on the type and structure of the polymer used. Since the elongational viscosity at the bubble wall during bubble growth also depends on these influencing factors, the so-called transient elongational viscosity plays a key role in describing the gas bubble growth behavior in polymer melts. The model-based description of the transient elongational viscosity function is difficult due to its dependence on time, Hencky strain and strain rate. Therefore, representative viscosities or shear viscosity models are usually used in the literature to predict the bubble growth behavior. In this work, the transient equibiaxial elongational viscosity function at the bubble wall during bubble growth is described holistically for the first time. This is achieved by extending the so-called molecular stress function (MSF) model by superposition principles (temperature, pressure and blowing agent concentration) and by using the elongational deformation behavior (Hencky strain and strain rate) at the bubble wall during the initial, and thus viscosity-driven, bubble growth process. Therefore, transient uniaxial elongational viscosity measurements are performed and the non-linear MSF model parameters of the two investigated polymers PS (linear polymer chains) and PLA (long-chain branched polymer chains) are determined. By applying the superposition principles and by changing the strain mode parameter to the equibiaxial case in the MSF model, the transient equibiaxial viscosity master curve is obtained and used to describe the bubble growth process. The results show that the extended MSF model can fully predict the transient equibiaxial elongational viscosity function at the bubble wall during bubble growth processes. The bubble growth behavior over time can then be realistically described using the defined transient equibiaxial elongational viscosity function at the bubble wall. This is not possible, for example, with a representative viscosity and therefore clearly demonstrates the influence and importance of knowing the transient deformation behavior that prevails at the bubble wall during bubble growth processes.

Socioeconomic and Medical Vulnerabilities Among Syrian Refugees with Non-communicable Diseases Attending Médecins Sans Frontières Services in Irbid, Jordan.

Non-communicable diseases (NCDs) are high-prevalence health problems among Syrian refugees. In 2014, Médecins Sans Frontières (MSF) identified unmet NCD care needs and began providing free-of-charge services for Syrian refugees in Irbid, Jordan. This study aimed to describe current socioeconomic and medical vulnerabilities among MSF Irbid Syrian refugee patients and their households and raise awareness of their ongoing health needs that must be addressed. A cross-sectional survey among Syrian refugees attending MSF NCD services in Irbid Governorate, Jordan was conducted by telephone interviews in January 2021 to query sociodemographic characteristics, economic situation, self-reported NCD prevalence, and Ministry of Health (MoH) policy awareness. Descriptive analysis of indicators included proportions or means presented with 95% confidence intervals. The survey included 350 patient-participants in 350 households and 2157 household members. Mean age was 28.3 years. Only 13.5% of household members had paid or self-employed work; 44% of households had no working members. Mean monthly income was 258.3 JOD (95%CI: 243.5-273.1) per household. Mean expenditures were 320.0 JOD (95%CI: 305.1-334.9). Debt was reported by 93% of households. NCD prevalence among adults was 42% (95%CI: 40-45). Hypertension was most prevalent (31.1%, 95%CI: 28.7-33.7), followed by diabetes (21.8%, 95%CI: 19.7-24.1) and cardiovascular diseases (14.4%, 95%CI: 12.6-16.4). Only 23% of interviewees were aware of subsidized MoH rates for NCD care. Twenty-nine percent stated they will not seek MoH care, mainly due to the unaffordable price. Our findings highlight increased vulnerability among MSF Irbid Syrian refugee NCD patients and their households, including: an older population; a high percentage of unemployment and reliance on cash assistance; higher proportion of households in debt and a high number of households having to resort to extreme coping mechanisms when facing a health emergency; and a higher proportion of people with multiple comorbid NCDs and physical disability. Their awareness of subsidised MoH care was low. MoH care is expected to be unaffordable for many. These people are at increased risk of morbidity and mortality. It is vital that health actors providing care for Syrian refugees take action to reduce their risk, including implementing financial support mechanisms and free healthcare.

Evaluation of the relation between the maxillary sinus and the posterior teeth using digital panoramic radiography.

This research aimed to determine the relationship between the maxillary posterior teeth and maxillary sinus floor (MSF), as well as the impact of nearby tooth loss on the space between MSF and posterior maxillary roots. A number of 120 digital panoramic radiographs were obtained from the archives of several clinics in Al-Najaf, Iraq, with the overall teeth examined in these radiographs including 236 of the 1st premolars, 227 of the 2nd premolars, 227 of the 1st molars, and 231 of the 2nd molars, from the right and left sides. The distances between the apices of the teeth and the maxillary sinus were determined. There are three categories of relationships between upper posterior teeth roots and MSF. These include type Os (root apex exists below or outside MSF), Type Co (root apex in contact with the MSF), and Type Is (root apex above or inside MSF). Type Os is the most encountered among premolars, Type Co is mostly encountered among the 2nd molars, and Type Is, in the 1st and 2nd molars. The study finds no correlation between age, gender, and the distribution of maxillary posterior tooth roots attached to the MSF. The first premolars were the furthest from MS, while the first molars were the closest. The most frequent link between maxillary molar roots and the MS was the Co-relation for the 2nd maxillary molar and the Is relation for the 1st maxillary molar. There is a non-significant decrease in the distance between the apices of the 1st maxillary premolar, 2nd maxillary premolar, and 1st maxillary molar and the MS before and after extraction.