Climate Variability and Ross River Virus Transmission in Townsville Region, Australia 1985 to 1996

Background How climate variability affects the transmission of infectious diseases at a regional level remains unclear. In this paper, we assessed the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. Methods Population-based information was obtained on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. The impact of climate variability on RRv transmission was assessed using the seasonal auto-regressive integrated moving average (SARIMA) model. Results There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (β=0.0012, p=0.04) and high tide (β=0.0262, p=0.01) were significantly associated with RRv transmission, although temperature and relative humidity did not seem to have played an important role in the Townsville region. Conclusions Rainfall, and high tide were likely to be key determinants of RRv transmission in the Townsville region

Changes in use of herbs and dietary supplements (HDS) among clinicians enrolled in an online curriculum

<p>Abstract</p> <p>Background</p> <p>Little is known about clinicians' use of herbs and dietary supplements (HDS), how their personal HDS use changes with time and training, and how changes in their personal use affect their confidence or communication with patients about HDS.</p> <p>Methods</p> <p>We conducted a prospective cohort study of clinicians before and after an on-line curriculum about HDS in winter-spring, 2005.</p> <p>Results</p> <p>Of the 569 clinicians who completed surveys both at baseline and after the course, 25% were male and the average age was 42 years old; 88% used HDS before and after the course. The average number of supplements used fell slightly from 6.2 at baseline to 5.8 after the course (P < 0.01). The most commonly used supplements at baseline were: multivitamins (65%), calcium (42%), B vitamins (34%), vitamin C (34%), green tea (27%), fish oil (27%) and vitamin E (25%). Use of fish oil increased to 30% after the course (P = 0.01). Use of supplements traditionally used to treat colds decreased: vitamin C (34% to 27%), zinc (13% to 10%), and echinacea (7% to 5%, P < 0.05 for all three). Changes in personal HDS use were not associated with significant changes in confidence or communication with patients.</p> <p>Conclusion</p> <p>Many clinicians use HDS personally; use changes seasonally and to a small extent with professional education. Professional use of HDS is dynamic and seasonal. Additional research is needed to understand the impact of personal use on professional attitudes and behavior in populations with lower baseline uses of HDS.</p

The long-term prediction of return to work following serious accidental injuries: A follow up study

Background Considerable indirect costs are incurred by time taken off work following accidental injuries. The aim of this study was to predict return to work following serious accidental injuries. Method 121 severely injured patients were included in the study. Complete follow-up data were available for 85 patients. Two weeks post trauma (T1), patients rated their appraisal of the injury severity and their ability to cope with the injury and its job-related consequences. Time off work was assessed at one (T2) and three years (T3) post accident. The main outcome was the number of days of sick leave taken due to the accidental injury. Results The patients' appraisals a) of the injury severity and b) of their coping abilities regarding the accidental injury and its job-related consequences were significant predictors of the number of sick-leave days taken. Injury severity (ISS), type of accident, age and gender did not contribute significantly to the prediction. Conclusions Return to work in the long term is best predicted by the patients' own appraisal of both their injury severity and the ability to cope with the accidental injury

Reciprocity as a foundation of financial economics

This paper argues that the subsistence of the fundamental theorem of contemporary financial mathematics is the ethical concept ‘reciprocity’. The argument is based on identifying an equivalence between the contemporary, and ostensibly ‘value neutral’, Fundamental Theory of Asset Pricing with theories of mathematical probability that emerged in the seventeenth century in the context of the ethical assessment of commercial contracts in a framework of Aristotelian ethics. This observation, the main claim of the paper, is justified on the basis of results from the Ultimatum Game and is analysed within a framework of Pragmatic philosophy. The analysis leads to the explanatory hypothesis that markets are centres of communicative action with reciprocity as a rule of discourse. The purpose of the paper is to reorientate financial economics to emphasise the objectives of cooperation and social cohesion and to this end, we offer specific policy advice

Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a clinically, genetically and pathologically heterogeneous disorder. Within FTLD with ubiquitin-positive inclusions (FTLD-U), a new pathological subtype named FTLD-FUS was recently found with fused in sarcoma (FUS) positive, TDP-43-negative inclusions, and striking atrophy of the caudate nucleus. The aim of this study was to determine the frequency of FTLD-FUS in our pathological FTLD series, and to describe the clinical, neuroimaging and neuropathological features of FTLD-FUS, especially caudate atrophy. Demographic and clinical data collected prospectively from 387 patients with frontotemporal dementia (FTD) yielded 74 brain specimens. Immunostaining was carried out using a panel of antibodies, including AT-8, ubiquitin, p62, FUS, and TDP-43. Cortical and caudate atrophy on MRI (n = 136) was rated as normal, mild-moderate or severe. Of the 37 FTLD-U cases, 33 were reclassified as FTLD-TDP and four (0.11, 95%: 0.00–0.21) as FTLD-FUS, with ubiquitin and FUS-positive, p62 and TDP-43-negative neuronal intranuclear inclusions (NII). All four FTLD-FUS cases had a negative family history, behavioural variant FTD (bvFTD), and three had an age at onset ≤40 years. MRI revealed mild-moderate or severe caudate atrophy in all, with a mean duration from onset till MRI of 63 months (range 16–119 months). In our total clinical FTD cohort, we found 11 patients (0.03; 95% CI: 0.01–0.05) with bvFTD, negative family history, and age at onset ≤40 years. Caudate atrophy was present in 10 out of 136 MRIs, and included all four FUS-cases. The newly identified FTLD-FUS has a frequency of 11% in FTLD-U, and an estimated frequency of three percent in our clinical FTD cohort. The existence of this pathological subtype can be predicted with reasonable certainty by age at onset ≤40 years, negative family history, bvFTD and caudate atrophy on MRI

Tigers Need Cover: Multi-Scale Occupancy Study of the Big Cat in Sumatran Forest and Plantation Landscapes

The critically endangered Sumatran tiger (Panthera tigris sumatrae Pocock, 1929) is generally known as a forest-dependent animal. With large-scale conversion of forests into plantations, however, it is crucial for restoration efforts to understand to what extent tigers use modified habitats. We investigated tiger-habitat relationships at 2 spatial scales: occupancy across the landscape and habitat use within the home range. Across major landcover types in central Sumatra, we conducted systematic detection, non-detection sign surveys in 47, 17×17 km grid cells. Within each cell, we surveyed 40, 1-km transects and recorded tiger detections and habitat variables in 100 m segments totaling 1,857 km surveyed. We found that tigers strongly preferred forest and used plantations of acacia and oilpalm, far less than their availability. Tiger probability of occupancy covaried positively and strongly with altitude, positively with forest area, and negatively with distance-to-forest centroids. At the fine scale, probability of habitat use by tigers across landcover types covaried positively and strongly with understory cover and altitude, and negatively and strongly with human settlement. Within forest areas, tigers strongly preferred sites that are farther from water bodies, higher in altitude, farther from edge, and closer to centroid of large forest block; and strongly preferred sites with thicker understory cover, lower level of disturbance, higher altitude, and steeper slope. These results indicate that to thrive, tigers depend on the existence of large contiguous forest blocks, and that with adjustments in plantation management, tigers could use mosaics of plantations (as additional roaming zones), riparian forests (as corridors) and smaller forest patches (as stepping stones), potentially maintaining a metapopulation structure in fragmented landscapes. This study highlights the importance of a multi-spatial scale analysis and provides crucial information relevant to restoring tigers and other wildlife in forest and plantation landscapes through improvement in habitat extent, quality, and connectivity

Evaluation of Force-Field Calculations of Lattice Energies on a Large Public Dataset, Assessment of Pharmaceutical Relevance, and Comparison to Density Functional Theory

Crystal lattice energy is a key property affecting the ease of processing pharmaceutical materials during manufacturing, as well as product performance. We present an extensive comparison of 324 force-field protocols for calculating the lattice energies of single component, organic molecular crystals (further restricted to Z′ less than or equal to one), corresponding to a wide variety of force-fields (DREIDING, Universal, CVFF, PCFF, COMPASS, COMPASSII), optimization routines, and other variations, which could be implemented as part of an automated workflow using the industry standard Materials Studio software. All calculations were validated using a large new dataset (SUB-BIG), which we make publicly available. This dataset comprises public domain sublimation data, from which estimated experimental lattice energies were derived, linked to 235 molecular crystals. Analysis of pharmaceutical relevance was performed according to two distinct methods based upon (A) public and (B) proprietary data. These identified overlapping subsets of SUB-BIG comprising (A) 172 and (B) 63 crystals, of putative pharmaceutical relevance, respectively. We recommend a protocol based on the COMPASSII force field for lattice energy calculations of general organic or pharmaceutically relevant molecular crystals. This protocol was the most highly ranked prior to subsetting and was either the top ranking or amongst the top 15 protocols (top 5%) following subsetting of the dataset according to putative pharmaceutical relevance. Further analysis identified scenarios where the lattice energies calculated using the recommended force-field protocol should either be disregarded (values greater than or equal to zero and/or the messages generated by the automated workflow indicate extraneous atoms were added to the unit cell) or treated cautiously (values less than or equal to −249 kJ/mol), as they are likely to be inaccurate. Application of the recommended force-field protocol, coupled with these heuristic filtering criteria, achieved an root mean-squared error (RMSE) around 17 kJ/mol (mean absolute deviation (MAD) around 11 kJ/mol, Spearman’s rank correlation coefficient of 0.88) across all 226 SUB-BIG structures retained after removing calculation failures and applying the filtering criteria. Across these 226 structures, the estimated experimental lattice energies ranged from −60 to −269 kJ/mol, with a standard deviation around 29 kJ/mol. The performance of the recommended protocol on pharmaceutically relevant crystals could be somewhat reduced, with an RMSE around 20 kJ/mol (MAD around 13 kJ/mol, Spearman’s rank correlation coefficient of 0.76) obtained on 62 structures retained following filtering according to pharmaceutical relevance method B, for which the distribution of experimental values was similar. For a diverse set of 17 SUB-BIG entries, deemed pharmaceutically relevant according to method B, this recommended force-field protocol was compared to dispersion corrected density functional theory (DFT) calculations (PBE + TS). These calculations suggest that the recommended force-field protocol (RMSE around 15 kJ/mol) outperforms PBE + TS (RMSE around 37 kJ/mol), although it may not outperform more sophisticated DFT protocols and future studies should investigate this. Finally, further work is required to compare our recommended protocol to other lattice energy calculation protocols reported in the literature, as comparisons based upon previously reported smaller datasets indicated this protocol was outperformed by a number of other methods. The SUB-BIG dataset provides a basis for these future studies and could support protocol refinement

Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis

Correction to Martin et al. available at: Genes & Development 30 (19): 2158 (http://genesdev.cshlp.org/content/31/9/953.full.pdf+html).Compaction of chromosomes is essential for accurate segregation of the genome duringmitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here,we report that biallelic mutations inNCAPD2,NCAPH, orNCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.This work was supported by funding from the Medical Research Council, the Lister Institute for Preventative Medicine, and the European Research Council (ERC; 281847 to A.P.J.); a Biotechnology and Biological Sciences Research Council grant (BB/ K017632/1 to P.V); a Sir Henry Dale Fellowship (grant 102560/ Z/13/Z to A.J.W.); Medical Research Scotland (to L.S.B.); the Potentials Foundation (to C.A.W.); and the Indian Council of Medical Research (BMS 54/2/2013 to S.R.P). The Deciphering Developmental Disorders Study presents independent research commissioned by the Health Innovation Challenge Fund (grant no. HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant no. WT098051). The views expressed here are those of the authors and not necessarily those of the Wellcome Trust or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83) granted by the Cambridge South Research Ethics Committee, and GEN/ 284/12 granted by the Republic of Ireland. We acknowledge the support of the National Institute for Health Research through the Comprehensive Clinical Research Network

Microservice Transition and its Granularity Problem: A Systematic Mapping Study

Microservices have gained wide recognition and acceptance in software industries as an emerging architectural style for autonomic, scalable, and more reliable computing. The transition to microservices has been highly motivated by the need for better alignment of technical design decisions with improving value potentials of architectures. Despite microservices' popularity, research still lacks disciplined understanding of transition and consensus on the principles and activities underlying "micro-ing" architectures. In this paper, we report on a systematic mapping study that consolidates various views, approaches and activities that commonly assist in the transition to microservices. The study aims to provide a better understanding of the transition; it also contributes a working definition of the transition and technical activities underlying it. We term the transition and technical activities leading to microservice architectures as microservitization. We then shed light on a fundamental problem of microservitization: microservice granularity and reasoning about its adaptation as first-class entities. This study reviews state-of-the-art and -practice related to reasoning about microservice granularity; it reviews modelling approaches, aspects considered, guidelines and processes used to reason about microservice granularity. This study identifies opportunities for future research and development related to reasoning about microservice granularity.Comment: 36 pages including references, 6 figures, and 3 table