Barriers to Buruli ulcer treatment completion in the Ashanti and Central Regions, Ghana.

BACKGROUND: Buruli ulcer is a chronic ulcerating skin condition, with the highest burden found in Central and West Africa where it disproportionately affects the most vulnerable populations. Treatment is demanding, comprising eight-weeks of daily antibiotics, regular wound care and possible surgical intervention. Treatment completion is key to optimising outcomes, however the degree of and barriers to this are not well understood. Recent change from injectable treatment (SR8) to oral treatment (CR8) has made it feasible to further decentralise care, potentially improving treatment access and completion. However, the impact of this and of other demographic and clinical influences on treatment completion must be explored first to ensure appropriate models of care are developed. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective clinical notes review and secondary data analysis of records from patients diagnosed between 1 January 2006-31 December 2018 at four district hospital clinics in the Ashanti and Central Regions, Ghana. Univariable analyses and multivariable logistic regression were performed to assess the association between explanatory variables and treatment completion. There were 931 patient episodes across the four clinics with overall treatment completion of 84.4%. CR8 was associated with higher treatment completion compared to SR8 (OR 4.1, P = 0.001). There was no statistically significant association found between distance from patient residence to clinic and treatment completion. CONCLUSIONS/SIGNIFICANCE: Improved treatment completion with CR8 supports its use as first line therapy and may enable decentralisation to fully community-based care. We did not find an association between distance to care and treatment completion, though analyses were limited by data availability. However, we did find evidence that distance to care continues to be associated with more severe forms of disease, which may reflect the higher costs of accessing care and lower awareness of the condition the further a patient lives. Decentralised care must therefore also continue to support community engagement and active outreach to identify cases early

Relation of mitral valve morphology and motion to mitral regurgitation severity in patients with mitral valve prolapse

<p>Abstract</p> <p>Background</p> <p>Mitral valve thickness is used as a criterion to distinguish the classical from the non-classical form of mitral valve prolapse (MVP). Classical form of MVP has been associated with higher risk of mitral regurgitation (MR) and concomitant complications. We sought to determine the relation of mitral valve morphology and motion to mitral regurgitation severity in patients with MVP.</p> <p>Methods</p> <p>We prospectively analyzed transthoracic echocardiograms of 38 consecutive patients with MVP and various degrees of MR. In the parasternal long-axis view, leaflets length, diastolic leaflet thickness, prolapsing depth, billowing area and non-coaptation distance between both leaflets were measured.</p> <p>Results</p> <p>Twenty patients (53%) and 18 patients (47%) were identified as having moderate to severe and mild MR respectively (ERO = 45 ± 27 mm²vs. 5 ± 7 mm², p < 0.001). Diastolic leaflet thickness was similar in both groups (5.5 ± 0.9 mm vs. 5.3 ± 1 mm, p = 0.57). On multivariate analysis, the non-coaptation distance (OR 7.9 per 1 mm increase; 95% CI 1.72-37.2) was associated with significant MR. Thick mitral valve leaflet as traditionally reported (≥ 5 mm) was not associated with significant MR (OR 0.9; 95% CI 0.2-3.4).</p> <p>Conclusions</p> <p>In patients with MVP, thick mitral leaflet is not associated with significant MR. Leaflet thickness is probably not as important in risk stratification as previously reported in patients with MVP. Other anatomical and geometrical features of the mitral valve apparatus area appear to be much more closely related to MR severity.</p

Inter-team Coordination in Large-Scale Agile Development: A Case Study of Three Enabling Mechanisms

Agile methods are increasingly used in large development projects, with multiple development teams. A central question is then what is needed to coordinate feature teams efficiently. This study exam- ines three mechanisms for coordination: Shared mental models, commu- nication and trust in a large-scale development project with 12 feature teams running over a four-year period. We analyse the findings in rela- tion to suggested frameworks for large-scale agile development and a theory on coordination, and provide new recommendations for practice and theory.Inter-team Coordination in Large-Scale Agile Development: A Case Study of Three Enabling MechanismspublishedVersio

Effect of combined treatment with alendronate and calcitriol on femoral neck strength in osteopenic rats

<p>Abstract</p> <p>Background</p> <p>Hip fracture is associated with pronounced morbidity and excess mortality in elderly women with postmenopausal osteoporosis. Many drugs have been developed to treat osteoporosis and to reduce the risk of osteoporotic fractures. We investigated the effects of combined alendronate and vitamin D₃treatment on bone mass and fracture load at the femoral neck in ovariectomized (OVX) rats, and evaluated the relationship between bone mass parameters and femoral neck strength.</p> <p>Methods</p> <p>Thirty 12-week-old female rats underwent either a sham-operation (n = 6) or OVX (n = 24). Twenty weeks later, OVX rats were further divided into four groups and received daily doses of either saline alone, 0.1 mg/kg alendronate, 0.1 μg/kg calcitriol, or a combination of both two drugs by continuous infusion via Alzet mini-osmotic pumps. The sham-control group received saline alone. After 12 weeks of treatment, femoral necks were examined using peripheral quantitative computed tomography (pQCT) densitometry and mechanical testing.</p> <p>Results</p> <p>Saline-treated OVX rats showed significant decreases in total bone mineral content (BMC) (by 28.1%), total bone mineral density (BMD) (by 9.5%), cortical BMC (by 26.3%), cancellous BMC (by 66.3%), cancellous BMD (by 29.0%) and total cross-sectional bone area (by 30.4%) compared with the sham-control group. The combined alendronate and calcitriol treatments improved bone loss owing to estrogen deficiency. On mechanical testing, although OVX significantly reduced bone strength of the femoral neck (by 29.3%) compared with the sham-control group, only the combined treatment significantly improved the fracture load at the femoral neck in OVX rats to the level of the sham-controls. The correlation of total BMC to fracture load was significant, but that of total BMD was not.</p> <p>Conclusion</p> <p>Our results showed that the combined treatment with alendronate and calcitriol significantly improved bone fragility of the femoral neck in OVX osteopenic rats.</p

SPG20 Protein Spartin Associates with Cardiolipin via Its Plant-Related Senescence Domain and Regulates Mitochondrial Ca2+ Homeostasis

Hereditary spastic paraplegias (HSPs) are a group of neurological disorders characterized clinically by spasticity of lower limbs and pathologically by degeneration of the corticospinal tract. Troyer syndrome is an autosomal recessive HSP caused by a frameshift mutation in the spartin (SPG20) gene. Previously, we established that this mutation results in a lack of expression of the truncated mutant spartin protein. Spartin is involved in many cellular processes and associates with several intracellular organelles, including mitochondria. Spartin contains a conserved plant-related senescence domain at its C-terminus. However, neither the function of this domain nor the roles of spartin in mitochondrial physiology are currently known. In this study, we determined that the plant-related senescence domain of spartin interacts with cardiolipin but not with two other major mitochondrial phospholipids, phosphatidylcholine and phosphatidylethanolamine. We also found that knockdown of spartin by small interfering RNA in a human neuroblastoma cell line resulted in depolarization of the mitochondrial membrane. In addition, depletion of spartin resulted in a significant decrease in both mitochondrial calcium uptake and mitochondrial membrane potential in cells treated with thapsigargin. Our results suggest that impairment of mitochondrial calcium uptake might contribute to the neurodegeneration of long corticospinal axons and the pathophysiology of Troyer syndrome

Trends in hospital admissions and mortality from asthma and chronic obstructive pulmonary disease in Australia, 1993-2003

The document attached has been archived with permission from the editor of the Medical Journal of Australia (8 May 2008). An external link to the publisher’s copy is includedObjective: To examine evolving changes in asthma and chronic obstructive pulmonary disease (COPD) in South Australia and Australia as a whole from the perspective of hospital admissions, ventilatory support and mortality data. Design: Retrospective analyses, for the period 1993–2003, of hospital separations data from the Australian Institute of Health and Welfare and the Integrated South Australian Activity Collection, and mortality data from the Australian Bureau of Statistics and South Australian hospital morbidity collection. Main outcome measures: Hospital separations, ventilatory support episodes, mortality rates, burden-of-disease rankings. Results: Between 1993 and 2003, in SA and nationally, hospital separations for asthma declined but separations for COPD increased significantly. Falling mortality rates from asthma in both men and women, and from COPD in men, contrast with increasing rates of COPD-related hospitalisation and mortality in women. Conclusions: Hospital admissions and mortality associated with asthma have fallen. Admission rates for COPD are declining for men, but there is no indication that admission rates for women have reached a peak. There is a need for higher prioritisation of COPD, including policies to reduce smoking in women, and medical practice initiatives to support primary and secondary prevention, pulmonary rehabilitation and appropriate drug therapies.David H Wilson, Graeme Tucker, Peter Frith, Sarah Appleton, Richard E Ruffin and Robert J Adam

Novel substituted methylenedioxy lignan suppresses proliferation of cancer cells by inhibiting telomerase and activation of c-myc and caspases leading to apoptosis

Conventional solvent fractionation and bioactivity based target assays were used to identify a new anti-cancer molecule from Phyllanthus urinaria, a herbal medicinal plant used in South India. At each step of the purification process the different fractions that were isolated were tested for specific anti-proliferative activity by assays measuring the inhibition of [3H]thymidine incorporation, and trypan blue drug exclusion. The ethyl acetate fraction that contained the bioactivity was further purified and resolved by HPLC on a preparative column. The purity of each of the fractions and their bioactivity were checked. Fraction 3 demonstrated a single spot on TLC and showed maximum anti-proliferative activity. This fraction was further purified and the structure was defined as 7′-hydroxy-3′,4′,5,9,9′-pentamethoxy-3,4-methylene dioxy lignan using NMR and mass spectrometry analysis. The pure compound and the crude ethyl acetate fraction which showed anti-proliferative activities were examined for ability to target specific markers of apoptosis like bcl2, c-myc and caspases and for effects on telomerase. Four specific cancer cell lines HEp2, EL-1 monocytes, HeLa and MCP7 were used in this study. The results indicate that 7′-hydroxy-3′,4′,5,9,9′-pentamethoxy-3,4-methylene dioxy lignan was capable of inhibiting telomerase activity and also could inhibit bcl2 and activate caspase 3 and caspase 8 whose significance in the induction of apoptosis is well known. We believe that this compound could serve as a valuable chemotherapeutic drug after further evaluations

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0