New Complexities and Approaches to Global Health Diplomacy: View from the U.S. Department of State

As part of the PLoS Medicine series on Global Health Diplomacy, Kerri-Ann Jones provides a perspective from the Inited States Department of State on current complexities and challenges in global health diplomacy

A Robust Pd-Catalyzed C-S Cross-Coupling Process Enabled by Ball-Milling

An operationally simple mechanochemical C–S coupling of aryl halides with thiols has been developed. The reaction process operates under benchtop conditions without the requirement for a (dry) solvent, an inert atmosphere, or catalyst preactivation. The reaction is finished within 3 h. The reaction is demonstrated across a broad range of substrates; the inclusion of zinc metal has been found to be critical in some instances, especially for coupling of alkyl thiols

Contaminants in Commercial Preparations of ‘Purified’ Small Leucine-Rich Proteoglycans May Distort Mechanistic Studies

This paper reports the perplexing results that came about because of seriously impure commercially available reagents. Commercial reagents and chemicals are routinely ordered by scientists and are expected to have been rigorously assessed for their purity. Unfortunately, we found this assumption to be risky. Extensive work was carried out within our laboratory using commercially-sourced preparations of the small leucine-rich proteoglycans, decorin and biglycan, to investigate their influence on nerve cell growth. Unusual results compelled us to analyse the composition and purity of both preparations of these proteoglycans using both mass spectrometry and Western blotting, with and without various enzymatic deglycosylations. Commercial ‘decorin’ and ‘biglycan’ were found to contain a mixture of proteoglycans including not only both decorin and biglycan but also fibromodulin and aggrecan. The unexpected effects of ‘decorin’ and ‘biglycan’ on nerve cell growth could be explained by these impurities. Decorin and biglycan contain either chondroitin or dermatan sulphate glycosaminoglycan chains whilst fibromodulin only contains keratan sulphate and the large (>2,500 kDa), highly glycosylated aggrecan, contains both keratan and chondroitin sulphate. The different structure, molecular weights and composition of these impurities significantly affected our work and any conclusions that could be made. These findings beg the question as to whether scientists need to verify the purity of each commercially obtained reagent used in their experiments. The implications of these findings are vast, since the effects of these impurities may already have led to inaccurate conclusions and reports in the literature with concomitant loss of researchers’ funds and time

A Case of Treatment Resistance and Complications in a Patient with Stiff Person Syndrome and Cerebellar Ataxia

BACKGROUND: Antibodies against glutamic acid decarboxylase (GAD) are associated with Stiff Person Syndrome (SPS). CASE REPORT: A 50-year-old woman presented with symptoms progressed over 9 years, resulting in a cerebellar ataxia and right upper limb tremor. Investigations revealed elevated serum and CSF anti-GAD antibody titres (98.6 and 53.4 μ/ml, respectively). Treatment included intravenous immunoglobulin and immunomodulation (infliximab and rituximab), improving her stiffness, but with no impact on the ataxia-related symptoms. Subsequent high-dose steroids led to diabetic ketoacidosis and unmasking of an insulin-dependent diabetes mellitus. DISCUSSION: This case illustrates several key features: (1) the combined clinical picture of SPS and cerebellar ataxia is a rare phenotype associated with anti-GAD antibodies; (2) the cerebellar ataxia described was progressive and poorly responsive to immunomodulatory therapy; and (3) the potential for development of further autoimmune sequelae in response to immunosuppression, namely, the development of insulin-dependent diabetes in response to treatment with high-dose oral steroids

Guidelines on "Standards of management of idiopathic scoliosis with corrective braces in everyday clinics and in clinical research": SOSORT Consensus 2008

<p>Abstract</p> <p>Background</p> <p>Reported failure rates,(defined based on percentage of cases progressing to surgery) of corrective bracing for idiopathic scoliosis are highly variable. This may be due to the quality of the brace itself, but also of the patient care during treatment. The latter is sometimes neglected, even though it is considered a main determinant of good results among conservative experts of SOSORT. The aim of this paper was to develop and verify the Consensus on management of scoliosis patients treated with braces</p> <p>Methods</p> <p>We followed a Delphi process in four steps, distributing and gradually changing according to the results a set of recommendations: we involved the SOSORT Board twice, then all SOSORT members twice, with a Pre-Meeting Questionnaire (PMQ), and during a Consensus Session at the SOSORT Athens Meeting with a Meeting Questionnaire (MQ). We set a 90% agreement as the minimum to be reached.</p> <p>Results</p> <p>We had a 71% response rate to PMQ, and 66.7% to MQ. Since the PMQ we had a good agreement (no answers below 72% – 70.2% over 90%). With the MQ the agreement consistently increased for all the answers previously below 90% (no answers below 83%, 75% over 90%). With increasing experience in bracing all numerical criteria tended to become more strict. We finally produced a set of 14 recommendations, grouped in 6 Domains (Experience/competence, Behaviours, Prescription, Construction, Brace Check, Follow-up).</p> <p>Conclusion</p> <p>The Consensus permits establishment of recommendations concerning the standards of management of idiopathic scoliosis with bracing, with the aim to increase efficacy and compliance to treatment. The SOSORT recommends to professionals engaged in patient care to follow the guidelines of this Consensus in their clinical practice. The SOSORT criteria should also be followed in clinical research studies to achieve a minimum quality of care. If the aim is to verify the efficacy of bracing these criteria should be companions of the methodological research criteria for bracing proposed by other societies.</p

Poor uptake of primary healthcare registration among recent entrants to the UK: a retrospective cohort study

Uptake of healthcare among migrants is a complex and controversial topic; there are multiple recognised barriers to accessing primary care. Delays in presentation to healthcare services may result in a greater burden on costly emergency care, as well as increased public health risks. This study aimed to explore some of the factors influencing registration of new entrants with general practitioners (GPs)

The pharmaceutical use of permethrin: Sources and behavior during municipal sewage treatment

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media, LLC.Permethrin entered use in the 1970s as an insecticide in a wide range of applications, including agriculture, horticultural, and forestry, and has since been restricted. In the 21st century, the presence of permethrin in the aquatic environment has been attributed to its use as a human and veterinary pharmaceutical, in particular as a pedeculicide, in addition to other uses, such as a moth-proofing agent. However, as a consequence of its toxicity to fish, sources of permethrin and its fate and behavior during wastewater treatment are topics of concern. This study has established that high overall removal of permethrin (approximately 90%) was achieved during wastewater treatment and that this was strongly dependent on the extent of biological degradation in secondary treatment, with more limited subsequent removal in tertiary treatment processes. Sources of permethrin in the catchment matched well with measured values in crude sewage and indicated that domestic use accounted for more than half of the load to the treatment works. However, removal may not be consistent enough to achieve the environmental quality standards now being derived in many countries even where tertiary treatment processes are applied.United Utilities PL

Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

Genetic Diversity of PCR-Positive, Culture-Negative and Culture-Positive Mycobacterium ulcerans Isolated from Buruli Ulcer Patients in Ghana.

Culture of Mycobacterium ulcerans from Buruli ulcer patients has very low sensitivity. Thus confirmation of M. ulcerans infection is primarily based on PCR directed against IS2404. In this study we compare the genotypes obtained by variable number of tandem repeat analysis of DNA from IS2404-PCR positive cultures with that obtained from IS2404 positive, culture-negative tissue. A significantly greater genetic heterogeneity was found among culture-negative samples compared with that found in cultured strains but a single genotype is over-represented in both sample sets. This study provides evidence that both the focal location of bacteria in a lesion as well as differences in the ability to culture a particular genotype may underlie the low sensitivity of culture. Though preliminary, data from this work also suggests that mycobacteria previously associated with fish disease (M. pseudoshottsii) may be pathogenic for humans