Bridging the gap between the distinct regulatory frameworks of international trade law and UN human rights law: Access to medicines

This research is focused on the complexity of two distinct legal frameworks, the World Trade Organization and the United Nations human rights systems, which converge on the issue of enhancing effective access to medicines for all. This research explores the intellectual property rules specifically in relation to patents, set out in the Agreement on Trade-Related Aspects of Intellectual Property Rights, administered by the World Trade Organization, for the purpose of understanding how these legal norms impact upon securing access to medicines. Measures intended to enhance access to medicines within this framework will also be explored in order to evaluate their effectiveness. This research also explores whether the issue of access to medicines can be considered within the context of a human right, through an examination of the UN human right systems, specifically in relation to the right to the highest attainable standard of physical and mental health under Article 12 of the International Covenant on Economic, Social and Cultural Rights. An analysis of the interpretation of this right will be undertaken, and an examination of the work of the UN human rights bodies to advance access to medicines will also be explored, in order to further understanding on the status of access to medicines within this framework. The purpose of this research is to highlight factors which may impede access to medicines and also potential factors for consideration when proposing solutions to this global concern. In order to further understanding of specific issues that impact on patients, two country case studies are also undertaken, to examine whether key themes emanating from earlier chapters are evident, and to provide insights into the challenges experienced at national level, as well as good practices that could help to inform policy at international level, for the purpose of enhancing access to medicines for all

Selected topics in the statistical mechanics of fluids.

The phase behaviour and thermodynamic properties of simple model mixtures are examined using the statistical associating fluid theory as extended to chain molecules interacting with potentials of variable range (SAFT-VR), and by computer simulation. The SAFT-VR approach is based on an accurate and compact representation of the free energy of chain molecules. We present the SA FT -VR methodology as applied to mixtures of non-conformal molecules. A series of mixing rules are presented, beginning with the van der Waals one-fluid prescription and including more complex treatments. The vapour-liquid equilibria of a mixture consisting of hard spheres and square-well monomers is examined with the SAFT-VR equation of state, together with the liquid-liquid equilibria of a symmetrical square-well mixture with no unlike interactions. Additionally, we examine the vapour-liquid equilibria of a square-well monomer-dimer mixture, composed of equal-sized segments, both with the SAFT-VR approach and by Gibbs ensemble Monte Carlo simulation. The simulation data are used to determine the vapourliquid critical line of the mixture. An extension of the SAFT-VR approach to describe the phase behaviour of chain molecules interacting with a soft repulsive potential and an attractive well of variable range is presented. We focus on the vapour-liquid properties of Lennard-Jones chains using a simple recipe for the evaluation of the chain free energy. We also perform a case study for a specific class of phase equilibria exhibited by binary mixtures, where systems are seen to posses a region of closed-loop immiscibility in their phase diagrams. We examine the nature of this type of pl1ase behaviour using the SA FT· VR equation of state and Gibbs ensemble simulation for a simple model system with an anisotropic bonding site, which is seen to be the governing factor in the appearance of the region of low-temperature miscibility for this system. The model is chosen in order to mimic the physical features of real systems which exhibit this type of re-entrant phase behaviour. The critical regions of this model are examined using a finite-size scaling analysis performed in the semigrand canonical ensemble

Engaging professional learners using the Virtual Learning Environment (VLE): a case study from social care

Virtual Learning Environments (VLEs) constitute an important resource for learners in Higher Education (HE), but data on the engagement of learners with VLEs is limited, particularly in the case of part-time, distance learners, and student engagement with VLEs may be lower than anticipated by institutions (Hopkins, 2011). This paper described a case study of a large group of WIWBL part-time, distance learners studying aspects of social care. A quantitative approach is taken to assess engagement with the Moodle VLE based on ‘page views’. 72% of enrolled students viewed one or more of the resources within the VLE ‘course’, and all resources present were viewed. The highest number of page-views was observed for resources such as ‘essential documents’ which are required for mandatory assessment tasks, whilst the lowest number of page-views appeared to be associated with information that students had received via other routes. Patterns of usage associated with demographic and achievement data are discussed. The paper considers reasons for the trends in engagement which may include the relatively high level of tutor contact and workplace support on this module. However, many part-time, distance learners do not have support of this type, and may display study behaviour which is even more strategic in terms of study approaches. The needs of such learners in relation to the effective use of VLEs and other appropriate technology is discussed, and recommendations are made for further study

Closed-loop phase equilibria of a symmetrical associating mixture of square-well molecules examined by Gibbs ensemble Monte Carlo simulation

A closed loop of liquid-liquid immiscibility for a simple model binary symmetrical mixture of square-well monomers with a single short-ranged interaction site has been recently observed using the Gibbs ensemble Monte Carlo technique @L. A. Davies, G. Jackson, and L. F. Rull, Phys. Rev. Lett. 82, 5285 ~1999!#. This model system has unfavorable mean-field interactions between unlike components which leads to phase separation at intermediate temperatures; the addition of a directional bonding site leads to association and miscibilty of the system at low temperatures. In this work we present a detailed study of the effect of a variation in pressure and of the strength of the bonding interaction on the phase equilibria of such a model system by Gibbs ensemble simulation. The phase diagram is dominated by regions of liquid-liquid immiscibility which are bounded at high temperatures by an upper critical solution temperature and by a lower critical solution temperature ~LCST! for specific values of the pressure and association strength. This closed-loop region is seen to increase in size as the pressure of the system is increased. For weak bonding interaction strengths the system does not possess a LCST and is seen to exhibit regions of two-phase vapor-liquid coexistence which are separated from the region of liquid-liquid immiscibility by a three-phase line. The phase equilibria of the same model system is also determined using the statistical associating fluid theory as adapted for potentials of variable range; the theory provides a good description of the closed-loop immiscibility and other features of the phase diagram

From words to actions: systematic review of interventions to promote sexual and reproductive health of persons with disabilities in low- and middle-income countries.

INTRODUCTION: Persons with disabilities have the same sexual and reproductive health and rights (SRHR) as non-disabled persons. Yet they face numerous barriers in their access to sexual and reproductive health services and their rights are often not met. Evidence on SRHR for persons with disabilities is sparse, particularly evaluations of interventions demonstrating 'what works.' This systematic review assessed interventions to promote SRHR for persons with disabilities in low- and middle-income countries. METHODS: We searched for qualitative, quantitative or mixed method observational studies representing primary research, published between 2010 and 2019, using MEDLINE, Embase, PubMed, Global Health and CINAHL Plus. Search strings were compiled for different elements of SRHR and for all forms of disability. 24,919 records were screened, leading to over 380 relevant papers, most of which were descriptive, focussing on needs and barriers to SRHR needs being fulfilled. Of the 33 full-text articles assessed for eligibility, 18 were included in the synthesis. All included studies were assessed for bias and quality of evidence, using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and RATS (relevance, appropriateness, transparency andsoundness) tools. Among the 16 interventions (from 18 articles), 25% had low risk of bias, 31% had moderate risk of bias and 44% had high risk of bias. Data analysis used narrative synthesis; a method suited for systematic reviews with heterogeneous studies. We used Levesque healthcare access model to analyse the focus of interventions. RESULTS: 11 interventions were from upper middle-income settings; two from lower-income settings; only one operated in rural areas. Interventions addressed intellectual impairment (6), visual impairment (6), hearing impairment (4), mental health conditions (2) and physical impairments (2). Most interventions (15/16) focus on information provision and awareness raising. We could not identify any intervention promoting access to maternal health, family planning and contraception, or safe abortion for people with disabilities. CONCLUSION: This systematic review has highlighted stark gaps in evidence. More rigorous evaluations are needed

The risk of cardiovascular disease in women after miscarriage, stillbirth, and therapeutic abortion: a protocol for a systematic review and meta-analysis

Funder: Homerton College, University of Cambridge (GB)Funder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272Abstract: Background: Cardiovascular disease (CVD) is the leading cause of death in women, responsible for approximately a third of all female deaths. Pregnancy complications are known to be associated with a greater risk of incident CVD in mothers. However, the relationships between pregnancy loss due to miscarriage, stillbirth, or therapeutic abortion, and future maternal cardiovascular health are under-researched. This study seeks to provide an up-to-date systematic review and meta-analysis of the relationship between these three forms of pregnancy loss and the subsequent development of CVD. Methods: This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis checklist (PRISMA) and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) Checklist. A systematic search will be undertaken using publications identified in MEDLINE (PubMed), Scopus, Web of Knowledge, the CINAHL Nursing Database, and the Cochrane Library. The eligibility of each publication will be determined by predefined selection criteria. The quality of the included studies will be rated using the Newcastle-Ottawa Scale. Pooled measures of association will be computed using random-effects model meta-analyses. Between-study heterogeneity will be assessed using the I2 statistic and the Cochrane χ2 statistic. Small study effects will be evaluated for meta-analyses with sufficient studies through the use of funnel plots and Egger’s test. Discussion: The results of this systematic review will discuss the long-term risks of multiple types of cardiovascular disease in women who have experienced miscarriage, stillbirth, and/or therapeutic abortion. It will contribute to the growing field of cardio-obstetrics as the first to consider the full breadth of literature regarding the association between all forms of pregnancy loss and future maternal cardiovascular disease. Systematic review registration: PROSPERO registration number [CRD42020167587

In vivo characterization of the role of tissue-specific translation elongation factor 1A2 in protein synthesis reveals insights into muscle atrophy

Translation elongation factor 1A2 (eEF1A2), uniquely among translation factors, is expressed specifically in neurons and muscle. eEF1A2‐null mutant wasted mice develop an aggressive, early‐onset form of neurodegeneration, but it is unknown whether the wasting results from denervation of the muscles, or whether the mice have a primary myopathy resulting from loss of translation activity in muscle. We set out to establish the relative contributions of loss of eEF1A2 in the different tissues to this postnatal lethal phenotype. We used tissue‐specific transgenesis to show that correction of eEF1A2 levels in muscle fails to ameliorate the overt phenotypic abnormalities or time of death of wasted mice. Molecular markers of muscle atrophy such as Fbxo32 were dramatically upregulated at the RNA level in wasted mice, both in the presence and in the absence of muscle‐specific expression of eEF1A2, but the degree of upregulation at the protein level was significantly lower in those wasted mice without transgene‐derived expression of eEF1A2 in muscle. This provides the first in vivo confirmation that eEF1A2 plays an important role in translation. In spite of the inability of the nontransgenic wasted mice to upregulate key atrogenes at the protein level in response to denervation to the same degree as their transgenic counterparts, there were no measurable differences between transgenic and nontransgenic wasted mice in terms of weight loss, grip strength, or muscle pathology. This suggests that a compromised ability fully to execute the atrogene pathway in denervated muscle does not affect the process of muscle atrophy in the short term

Results From Wales’ 2018 Report Card on Physical Activity for Children and Youth

This is the third Active Healthy Kids Wales (AHK-Wales) Report Card following the inaugural and second report card published in 2014 and 2016 respectively.1,2 The 2018 report card (Figure 1) consolidates and translates research related to physical activity among children and young people in Wales. The report card aimed to raise the awareness of children and young people’s engagement in physical activity behaviours and influences, and advocate for children’s right to be active and healthy

Haploinsufficiency for Translation Elongation Factor eEF1A2 in Aged Mouse Muscle and Neurons Is Compatible with Normal Function

Translation elongation factor isoform eEF1A2 is expressed in muscle and neurons. Deletion of eEF1A2 in mice gives rise to the neurodegenerative phenotype "wasted" (wst). Mice homozygous for the wasted mutation die of muscle wasting and neurodegeneration at four weeks post-natal. Although the mutation is said to be recessive, aged heterozygous mice have never been examined in detail; a number of other mouse models of motor neuron degeneration have recently been shown to have similar, albeit less severe, phenotypic abnormalities in the heterozygous state. We therefore examined the effects of ageing on a cohort of heterozygous +/wst mice and control mice, in order to establish whether a presumed 50% reduction in eEF1A2 expression was compatible with normal function. We evaluated the grip strength assay as a way of distinguishing between wasted and wild-type mice at 3-4 weeks, and then performed the same assay in older +/wst and wild-type mice. We also used rotarod performance and immunohistochemistry of spinal cord sections to evaluate the phenotype of aged heterozygous mice. Heterozygous mutant mice showed no deficit in neuromuscular function or signs of spinal cord pathology, in spite of the low levels of eEF1A2

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder