An Automated Image Analysis System to Quantify Endosomal Tubulation.

Recycling of cargos from early endosomes requires regulation of endosomal tubule formation and fission. This regulation is disrupted in cells depleted of the microtubule severing enzyme spastin, causing elongation of endosomal tubules and mis-trafficking of recycling endosomal cargos such as the transferrin receptor. Spastin is encoded by SPAST, mutations in which are the most frequent cause of autosomal dominant hereditary spastic paraplegia, a condition characterised by a progressive loss of lower limb function resulting from upper motor neuron axonopathy. Investigation of molecular factors involved in endosomal tubule regulation is hindered by the need for manual counting of endosomal tubules. We report here the development of an open source automated system for the quantification of endosomal tubules, using ImageJ and R. We validate the method in cells depleted of spastin and its binding partner IST1. The additional speed and reproducibility of this system compared with manual counting makes feasible screens of candidates to further understand the mechanisms of endosomal tubule formation and fission.This work was supported by grants to ER; UK Medical Research Council Project Grant [MR/M00046X/1], Wellcome Trust Senior Research Fellowship in Clinical Science [082381], Project Grants from United States Spastic Paraplegia Foundation and from the Tom Wahlig Stiftung. TMN was supported by MRC PhD studentship [G0800117]. CIMR is supported by a Wellcome Trust Strategic Award [100140] and Equipment Grant [093026]

Renal impairment in a rural African antiretroviral programme

Background: There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods: (i) Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii) A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR) of significantly impaired renal function (combining severe and moderate impairment). Co-variates for analysis were age, sex and CD4 count at initiation. Results: (i) There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8) whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5) with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl). In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1), male gender (aOR 1.89, 95% C.I. 1.39–2.56) and CD4<100 cells/ul (aOR 1.4, 95% C.I. 1.07–1.82) were associated with risk of significant renal impairment (ii) In 149 consecutive patients, urine analysis had poor sensitivity and specificity for detecting impaired renal function. Conclusion: In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited

Life satisfaction in coastal Kenya and Mozambique reflects culture, gendered relationships and security of basic needs: Implications for ecosystem services

This is the final version. Available from Elsevier via the DOI in this record. Data availability: Data are published in https://reshare.ukdataservice.ac.ukLife satisfaction is both a desirable ‘end’ for sustainable development, and a means to understand the priorities, and behaviour of people towards local ecosystems. Ecosystem-services research on life satisfaction has focused on cultural services in wealthy, Western contexts, although ecosystem services are essential for poor people's livelihoods in the Global South. We examined reported life satisfaction from a survey of over 2000 people in rural and urban settings of coastal Kenya and Mozambique. We coded respondents’ open-ended reasons for their reported satisfaction, and used multiple correspondence analysis to explore the characteristics of people who mentioned different reasons. We tested associations between satisfaction and the meeting of basic needs and income, with binary logistic regression, accounting for site and gender. Life satisfaction was lower in Kenya, for men, and in the most urbanised site. Respondents explained high, and low, satisfaction in terms of social relationships, basic needs, money and employment. They rarely mentioned the ecosystem services and related livelihoods that underpin those, suggesting an instrumental relation to nature. Meeting basic needs, including economic security better predicted satisfaction than household income. Life satisfaction reflected material differences in people's lives but also different evaluative criteria and national cultures. For example, family reasons more commonly explained women's satisfaction, while money was more important for urban-dwelling men. We propose that the holistic perspective offered by life-satisfaction research can inform environmental management alongside more focused ecosystem-service research. For example, our results suggest that a) interventions should recognise immediate needs and social relationships, b) the role of ecosystem services for subjective wellbeing varies by local culture and individual identities and c) secure and fair access to ecosystem services may support life satisfaction better than high incomes that are insecure or inequitably distributed.Economic and Social Research Council (ESRC)Department for International Development (DFID)Natural Environment Research Council (NERC

Identification of hip fracture patients from radiographs using Fourier analysis of the trabecular structure: a cross-sectional study

Peer reviewedPublisher PD

Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions

We report on a search for metastable positively and negatively charged states of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864. We have sampled approximately six billion 10% most central Au+Pb interactions and have observed no strangelet states (baryon number A < 100 droplets of strange quark matter). We thus set upper limits on the production of these exotic states at the level of 1-6 x 10^{-8} per central collision. These limits are the best and most model independent for this colliding system. We discuss the implications of our results on strangelet production mechanisms, and also on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover memorial edition

Quantifying morbidities by Adjusted Clinical Group system for a Taiwan population: A nationwide analysis

<p>Abstract</p> <p>Background</p> <p>The Adjusted Clinical Group (ACG) system has been used in measuring an individual's and a population's morbidities. Although all required inputs for running the ACG system are readily available, patients' morbidities and their associations to health care utilizations have been rarely studied in Taiwan. Therefore, the objective of this study was using the ACG system to quantify morbidities for Taiwanese population and to examine their relationship to ambulatory utilizations and costs.</p> <p>Methods</p> <p>This secondary analysis examined claims data for ambulatory services provided to 2.71 million representative Taiwanese in 2002 and 2003. People were grouped by the ACG system according to age, gender, and all ambulatory diagnosis codes in a given year. The software collapses the full set of ACGs into six morbidity categories (Non-users, Healthy, Low-morbidity, Moderate-, High- and Very-high) termed Resource Utilization Bands (RUBs). Each ACG was assigned a relative weight (RW), which was calculated as the ratio of mean ambulatory cost for each ACG to that for the overall. The distribution of morbidities was compared between years 2002 and 2003. The consistency of the distributions of visits, costs, and RWs of each ACG were examined for a two-year period. The relationship between people's morbidities and their ambulatory utilizations and costs was assessed.</p> <p>Results</p> <p>Ninety-eight percent of the subjects were correctly assigned to ACGs. Except for non-users (7.9 ~ 8.3%), most subjects were assigned to ACGs of acute and minor diseases and ACGs of moderate-to-high-morbid chronic diseases. The distributions of ACG-based morbidities were highly consistent (r = 0.949, <it>p < 0.001</it>) between 2002 and 2003. The ACG-specific visits (r = 0.955, <it>p < 0.001</it>), costs (r = 0.966, <it>p < 0.001</it>) and RWs (r = 0.991, <it>p < 0.001</it>) were correlated across two years. People grouped to the high-morbid ACGs had more visits and costs than those grouped to the low-morbid ACGs. Forty-six percent of the total ambulatory costs were spent by eighteen percent of the population, who were grouped to the High- and Very-high-morbidity RUBs.</p> <p>Conclusion</p> <p>This study demonstrated the feasibility, validity, and reliability of using the ACG system to measure morbidities in a Taiwan population and to explain their associations with ambulatory utilizations and costs for the whole country.</p

Complex patterns of human antisera reactivity to novel 2009 H1N1 and historical H1N1 influenza strains

Background: During the 2009 influenza pandemic, individuals over the age of 60 had the lowest incidence of infection with approximately 25% of these people having pre-existing, cross-reactive antibodies to novel 2009 H1N1 influenza isolates. It was proposed that older people had pre-existing antibodies induced by previous 1918-like virus infection(s) that cross-reacted to novel H1N1 strains. Methodology/Principal Findings: Using antisera collected from a cohort of individuals collected before the second wave of novel H1N1 infections, only a minority of individuals with 1918 influenza specific antibodies also demonstrated hemagglutination-inhibition activity against the novel H1N1 influenza. In this study, we examined human antisera collected from individuals that ranged between the ages of 1 month and 90 years to determine the profile of seropositive influenza immunity to viruses representing H1N1 antigenic eras over the past 100 years. Even though HAI titers to novel 2009 H1N1 and the 1918 H1N1 influenza viruses were positively associated, the association was far from perfect, particularly for the older and younger age groups. Conclusions/Significance: Therefore, there may be a complex set of immune responses that are retained in people infected with seasonal H1N1 that can contribute to the reduced rates of H1N1 influenza infection in older populations. © 2012 Carter et al

Kinship Index Variations among Populations and Thresholds for Familial Searching

Current familial searching strategies are developed primarily based on autosomal STR loci, since most of the offender profiles in the forensic DNA databases do not contain Y-STR or mitochondrial DNA data. There are generally two familial searching methods, Identity-by-State (IBS) based methods or kinship index (KI) based methods. The KI based method is an analytically superior method because the allele frequency information is considered as opposed to solely allele counting. However, multiple KIs should be calculated if the unknown forensic profile may be attributed to multiple possible relevant populations. An important practical issue is the KI threshold to select for limiting the list of candidates from a search. There are generally three strategies of setting the KI threshold for familial searching: (1) SWGDAM recommendation 6; (2) minimum KI≥KI threshold; and (3) maximum KI≥KI threshold. These strategies were evaluated and compared by using both simulation data and empirical data. The minimum KI will tend to be closer to the KI appropriate for the population of which the forensic profile belongs. The minimum KI≥KI threshold performs better than the maximum KI≥KI threshold. The SWGDAM strategy may be too stringent for familial searching with large databases (e.g., 1 million or more profiles), because its KI thresholds depend on the database size and the KI thresholds of large databases have a higher probability to exclude true relatives than smaller databases. Minimum KI≥KI threshold strategy is a better option, as it provides the flexibility to adjust the KI threshold according to a pre-determined number of candidates or false positive/negative rates. Joint use of both IBS and KI does not significantly reduce the chance of including true relatives in a candidate list, but does provide a higher efficiency of familial searching

Counting and effective rigidity in algebra and geometry

The purpose of this article is to produce effective versions of some rigidity results in algebra and geometry. On the geometric side, we focus on the spectrum of primitive geodesic lengths (resp., complex lengths) for arithmetic hyperbolic 2-manifolds (resp., 3-manifolds). By work of Reid, this spectrum determines the commensurability class of the 2-manifold (resp., 3-manifold). We establish effective versions of these rigidity results by ensuring that, for two incommensurable arithmetic manifolds of bounded volume, the length sets (resp., the complex length sets) must disagree for a length that can be explicitly bounded as a function of volume. We also prove an effective version of a similar rigidity result established by the second author with Reid on a surface analog of the length spectrum for hyperbolic 3-manifolds. These effective results have corresponding algebraic analogs involving maximal subfields and quaternion subalgebras of quaternion algebras. To prove these effective rigidity results, we establish results on the asymptotic behavior of certain algebraic and geometric counting functions which are of independent interest.Comment: v.2, 39 pages. To appear in Invent. Mat