What are the priorities for improving cataract surgical outcomes in Africa? Results of a Delphi exercise.

PURPOSE: The quality of cataract surgery delivered in sub-Saharan Africa (SSA) is a significant constraint to achieving the elimination of avoidable blindness. No published reports from routine SSA cataract services attain the WHO benchmarks for visual outcomes; poor outcomes (<6/60) often comprise 20% in published case series. This Delphi exercise aimed to identify and prioritise potential interventions for improving the quality of cataract surgery in SSA to guide research and eye health programme development. METHODS: An initial email open-question survey created a ranked list of priorities for improving quality of surgical services. A second-round face-to-face discussion facilitated at a Vision 2020 Research Mentorship Workshop in Tanzania created a refined list for repeated ranking. RESULTS: Seventeen factors were agreed that might form target interventions to promote quality of cataract services. Improved training of surgeons was the top-ranked item, followed by utilisation of biometry, surgical equipment availability, effective monitoring of outcomes of cataract surgery by the surgeon, and well-trained support staff for the cataract pathway (including nurses seeing post-operative cases). CONCLUSION: Improving the quality of cataract surgery in SSA is a clinical, programmatic and public health priority. In the absence of other evidence, the collective expert opinion of those involved in ophthalmic services regarding the ranking of factors to promote quality improvement, refined through this Delphi exercise, provides us with candidate intervention areas to be evaluated

The incorporation of carbon nanofibres to enhance the properties of hot compacted self-reinforced single polymer composites

Nanoscale fillers offer the potential for significant enhancement of a range of polymer properties, as they are available in a wide variety of shapes and properties. Carbon nanotubes (CNT) and nanofibres (CNF) have been used extensively in the literature, yet very few analytical studies of the material properties have been reported. Here we use the Cox-Krenchel model to interpret the experimentally measured changes in Young’s modulus from particle aspect ratio reduction during to processing, in addition to the measurement of the mechanical properties of the composite. Hot Compaction, a process developed at the University of Leeds [1], utilises high modulus, highly oriented elements to form thick section, homogeneous sheets without the need to introduce a second phase of different chemical composition. These ‘single polymer’ composites are produced by selective melting on the surface of the oriented elements; on cooling, this molten material re-crystallises to form a matrix phase and bind the oriented elements together. CNF filled polypropylene (PP) tapes have been produced and successfully hot compacted into sheets. The properties of these nanofilled self-reinforced single polymer composites is reported. Of particular interest has been to investigate the introduction of interleaved films, an extension of recent work conducted by two of this papers authors [2] of the same polymer or nanocomposite in order to establish the change in properties when the CNF are incorporated in the drawn tapes, in the interleaved films or both

In search of a working notion of lex sportiva

The emergence of a lex specialis regime and its interaction with the established, governing lex generalis in their overlapping spheres of application is always an intriguing legal relationship to explore. In this article, the focus will be on the development of legal principles and rules that have been/can be collectively described as lex sportiva. However, it is notable that those involved in the consideration, usage and application of this notion have not agreed as to the scope and delimitation of the concept. It is debated whether lex sportiva exists in the first place, its legal sources and its purpose. The risk is for the concept becoming redundant when not vilified as a hidden strategy to exclude non-sports-related law from the ambit of sport. Through an examination of the different propositions to the framework of the term, this article will shed light on the existence, utility and limits of the development of this conceptualisation

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Barriers to Remote Health Interventions for Type 2 Diabetes: A Systematic Review and Proposed Classification Scheme

BACKGROUND: Diabetes self-management involves adherence to healthy daily habits typically involving blood glucose monitoring, medication, exercise, and diet. To support self-management, some providers have begun testing remote interventions for monitoring and assisting patients between clinic visits. Although some studies have shown success, there are barriers to widespread adoption. OBJECTIVE: The objective of our study was to identify and classify barriers to adoption of remote health for management of type 2 diabetes. METHODS: The following 6 electronic databases were searched for articles published from 2010 to 2015: MEDLINE (Ovid), Embase (Ovid), CINAHL, Cochrane Central, Northern Light Life Sciences Conference Abstracts, and Scopus (Elsevier). The search identified studies involving remote technologies for type 2 diabetes self-management. Reviewers worked in teams of 2 to review and extract data from identified papers. Information collected included study characteristics, outcomes, dropout rates, technologies used, and barriers identified. RESULTS: A total of 53 publications on 41 studies met the specified criteria. Lack of data accuracy due to input bias (32%, 13/41), limitations on scalability (24%, 10/41), and technology illiteracy (24%, 10/41) were the most commonly cited barriers. Technology illiteracy was most prominent in low-income populations, whereas limitations on scalability were more prominent in mid-income populations. Barriers identified were applied to a conceptual model of successful remote health, which includes patient engagement, patient technology accessibility, quality of care, system technology cost, and provider productivity. In total, 40.5% (60/148) of identified barrier instances impeded patient engagement, which is manifest in the large dropout rates cited (up to 57%). CONCLUSIONS: The barriers identified represent major challenges in the design of remote health interventions for diabetes. Breakthrough technologies and systems are needed to alleviate the barriers identified so far, particularly those associated with patient engagement. Monitoring devices that provide objective and reliable data streams on medication, exercise, diet, and glucose monitoring will be essential for widespread effectiveness. Additional work is needed to understand root causes of high dropout rates, and new interventions are needed to identify and assist those at the greatest risk of dropout. Finally, future studies must quantify costs and benefits to determine financial sustainability

Marine anthropogenic litter on British beaches: a 10-year nationwide assessment using citizen science data

Growing evidence suggests that anthropogenic litter, particularly plastic, represents a highly pervasive and persistent threat to global marine ecosystems. Multinational research is progressing to characterise its sources, distribution and abundance so that interventions aimed at reducing future inputs and clearing extant litter can be developed. Citizen science projects, whereby members of the public gather information, offer a low-cost method of collecting large volumes of data with considerable temporal and spatial coverage. Furthermore, such projects raise awareness of environmental issues and can lead to positive changes in behaviours and attitudes. We present data collected over a decade (2005-2014 inclusive) by Marine Conservation Society (MCS) volunteers during beach litter surveys carried along the British coastline, with the aim of increasing knowledge on the composition, spatial distribution and temporal trends of coastal debris. Unlike many citizen science projects, the MCS beach litter survey programme gathers information on the number of volunteers, duration of surveys and distances covered. This comprehensive information provides an opportunity to standardise data for variation in sampling effort among surveys, enhancing the value of outputs and robustness of findings. We found that plastic is the main constituent of anthropogenic litter on British beaches and the majority of traceable items originate from land-based sources, such as public littering. We identify the coast of the Western English Channel and Celtic Sea as experiencing the highest relative litter levels. Increasing trends over the 10-year time period were detected for a number of individual item categories, yet no statistically significant change in total (effort-corrected) litter was detected. We discuss the limitations of the dataset and make recommendations for future work. The study demonstrates the value of citizen science data in providing insights that would otherwise not be possible due to logistical and financial constraints of running government-funded sampling programmes on such large scales

Affinity labeling of the active site of Escherichia coli glutamine synthetase by 5'-p-fluorosulfonylbenzoyladenosine.

The interaction of Escherichia coli glutamine synthetase with the adenosine 5'-triphosphate analogue, 5'-p-fluorosulfonylbenzoyladenosine (5'-FSO2BzAdo), has been studied. This interaction results in the covalent attachment of the 5'-FSO2BzAdo to the enzyme with concomitant loss of catalytic activity. Although adenine nucleotides interact with glutamine synthetase at three distinct sites--a noncovalent AMP effector site, a regulatory site of covalent adenylylation, and the catalytic ATP/ADP binding site--our studies suggest that reaction with 5'-FSO2BzAdo occurs only at the active center. When glutamine synthetase was incubated with 5'-FSO2BzAdo, the decrease in catalytic activity obeyed pseudo-first order kinetics. The plot of the observed rate constant of inactivation versus the concentration of 5'-FSO2BzAdo was hyperbolic, consistent with reversible binding of the analogue to the enzyme prior to covalent attachment. Protection against inactivation was afforded by ATP and ADP; L-glutamate did not protect the enzyme against inactivation, but rather enhanced the rate of inactivation, consistent with the observations of others (Timmons, R. B., Rhee, S. G., Luterman, D. L., and Chock, P. B. (1974) Biochemistry 13, 4479-4485) that there is synergism in the binding of the two substrates to the enzyme. The incorporation of approximately 1.09 mol of the 5'-FSO2BzAdo/mol of glutamine synthetase subunit resulted in the total loss of enzymatic activity. The results suggest that 5'-FSO2BzAdo occupies the ATP binding site at the active center of glutamine synthetase and binds covalently to an amino acid residue nearby

Calculating metalation in cells reveals CobW acquires Co(II) for vitamin B12 biosynthesis while related proteins prefer Zn(II)

Protein metal-occupancy (metalation) in vivo has been elusive. To address this challenge, the available free energies of metals have recently been determined from the responses of metal sensors. Here, we use these free energy values to develop a metalation-calculator which accounts for inter-metal competition and changing metal-availabilities inside cells. We use the calculator to understand the function and mechanism of GTPase CobW, a predicted CoII-chaperone for vitamin B12. Upon binding nucleotide (GTP) and MgII, CobW assembles a high-affinity site that can obtain CoII or ZnII from the intracellular milieu. In idealised cells with sensors at the mid-points of their responses, competition within the cytosol enables CoII to outcompete ZnII for binding CobW. Thus, CoII is the cognate metal. However, after growth in different [CoII], CoII-occupancy ranges from 10 to 97% which matches CobW-dependent B12 synthesis. The calculator also reveals that related GTPases with comparable ZnII affinities to CobW, preferentially acquire ZnII due to their relatively weaker CoII affinities. The calculator is made available here for use with other proteins

Pregnancy outcome in women with Gaucher disease type 1 who had unplanned pregnancies during eliglustat clinical trials

Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficient enzymatic activity of acid β-glucosidase, resulting in accumulation of its substrate glucosylceramide, leading to debilitating visceral, hematologic, and skeletal manifestations. Women with GD1 are at increased risk for complications during pregnancy, delivery, and postpartum. Treatment with enzyme replacement therapy is generally recommended before and during pregnancy to reduce risks. Eliglustat, an oral substrate-reduction therapy, is a first-line treatment for adults with GD1 adults who have extensive, intermediate, or poor CYP2D6-metabolizer phenotypes (>90% of patients). We report on pregnancy outcomes among women in eliglustat trials who had unplanned pregnancies and female partners of men in the trials. In four phase 2 and 3 eliglustat trials of 393 adults with GD1, women of childbearing potential were required to use contraception, have monthly pregnancy tests, and discontinue eliglustat promptly if pregnant. In phase 2 and 3 trials, 18 women had 19 pregnancies, resulting in 14 healthy infants from 13 pregnancies (one set of twins), three elective terminations, one ectopic pregnancy, one spontaneous abortion, and one in utero death. Median estimated eliglustat exposure duration during pregnancy was 38 days. In phase 1 trials (non-GD1 subjects), one woman had a spontaneous abortion. Partners of 16 eliglustat-treated men with GD1 had 18 pregnancies, all resulting in healthy infants. Eliglustat is not approved during pregnancy due to limited data. Guidelines for clinicians and patients with GD that address use of eliglustat in women of childbearing potential are needed