A comparative phylogenetic approach to Austronesian cultural evolution

Phylogenetic comparative methods were used to test hypotheses about cultural evolution in ethnolinguistic groups from the Austronesian language family of the Pacific. The case for quantitative statistical approaches to the empirical evolution of linguistic and cultural features was presented. Phylogenetic trees of 67 Austronesian languages were constructed using maximum parsimony and Bayesian Markov Chain Monte Carlo likelihood algorithms on a database of lexical items. The predominant transmission mode of 76 cultural traits was examined at the macroevolutionary level with (i) partial Mantel matrix tests and (ii) multiple regression on phylogenetic and geographic nearest neighbours. Mantel tests showed that both geographic and phylogenetic transmission was correlated with cultural diversity. Geographic distance had a greater overall partial correlation with cultural distance than did phylogenetic distance, but only phylogenetic correlations were found with kinship/social traits. Multiple regression on individual traits found that phylogenetic nearest neighbours predicted more cultural traits, especially those involving the inheritance of resources. Ancestral states of kinship traits were reconstructed using a Bayesian comparative method on a sample of 1000 phylogenies. The root of the tree was reconstructed as having matrilocal post-marital residence and a bilateral, flexible descent system. Proto Oceanic was reconstructed as unilocal and unilineal, and an hypothesis of matriliny and matrilocality could not be rejected. Murdock's main-sequence theory of the co-evolution of post-marital residence and descent systems was tested. The most likely model of the evolutionary pathway demonstrated that residence changed before descent. Rates of change in residence and descent traits were estimated. A co-evolutionary hypothesis of matriliny and male absence was tested. Contrary to anthropological theory, a high dependence on fishing showed no clear pattern of co-evolution with matrilineal social organisation. Population size of the language community was hypothesized to be a factor influencing lexical change. Conventional statistics showed a significant strong inverse correlation, indicating a relationship between small populations and accelerated lexical change. This correlation disappeared when comparative methods were used to control for phylogeny. Population size appeared to be evolving according to a drift model, while lexical change did not fit a neutral model of evolution

Differential Geometry of Quantum States, Observables and Evolution

The geometrical description of Quantum Mechanics is reviewed and proposed as an alternative picture to the standard ones. The basic notions of observables, states, evolution and composition of systems are analised from this perspective, the relevant geometrical structures and their associated algebraic properties are highlighted, and the Qubit example is thoroughly discussed.Comment: 20 pages, comments are welcome

The UK's Global Health Respiratory Network: Improving respiratory health of the world's poorest through research collaborations.

Respiratory disorders are responsible for considerable morbidity, health care utilisation, societal costs and approximately one in five deaths worldwide [1-4]. Yet, despite this substantial health and societal burden – which particularly affects the world’s poorest populations and as such is a major contributor to global health inequalities – respiratory disorders have historically not received the policy priority they warrant. For example, despite causing an estimated 1000 deaths per day, less than half of the world’s countries collect data on asthma prevalence (http://www.globalasthmareport.org/). This is true for both communicable and non-communicable respiratory disorders, many of which are either amenable to treatment or preventable

Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial

Background Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges. Methods We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented). Results At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points. Conclusion In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes

A cross sectional study of requests for knee radiographs from primary care

<p>Abstract</p> <p>Background</p> <p>Knee pain is the commonest pain complaint amongst older adults in general practice. General Practitioners (GPs) may use x rays when managing knee pain, but little information exists regarding this process. Our objectives, therefore, were to describe the information GPs provide when ordering knee radiographs in older people, to assess the association between a clinical diagnosis of osteoarthritis (OA) and the presence of radiographic knee OA, and to investigate the clinical content of the corresponding radiologists' report.</p> <p>Methods</p> <p>A cross sectional study of GP requests for knee radiographs and their matched radiologists' reports from a local radiology department. Cases, aged over 40, were identified during an 11-week period. The clinical content of the GPs' requests and radiologists' reports was analysed. Associations of radiologists' reporting of i) osteoarthritis, ii) degenerative disease and iii) individual radiographic features of OA, with patient characteristics and clinical details on the GPs' requests, were assessed.</p> <p>Results</p> <p>The study identified 136 cases with x ray requests from 79 GPs and 11 reporting radiologists. OA was identified clinically in 19 (14%) of the requests, and queried in another 31 (23%). The main clinical descriptor was pain in 119 cases (88%). Radiologists' reported OA in 22% of cases, and the features of OA were mentioned in 63%. Variation in reporting existed between radiologists. The commonest description was joint space narrowing in 52 reports (38%). There was an apparent although non significant increase in the reporting of knee OA when the GP had diagnosed or queried it (OR 1.95; 95% CI 0.76, 5.00).</p> <p>Conclusion</p> <p>The features of radiographic OA are commonly reported in those patients over 40 whom GPs send for x ray. If OA is clinically suspected, radiologists appear to be more likely to report its presence. Further research into alternative models of referral and reporting might identify a more appropriate imaging policy in knee disorders for primary care.</p

Structural Basis for Mitotic Centrosome Assembly in Flies.

In flies, Centrosomin (Cnn) forms a phosphorylation-dependent scaffold that recruits proteins to the mitotic centrosome, but how Cnn assembles into a scaffold is unclear. We show that scaffold assembly requires conserved leucine zipper (LZ) and Cnn-motif 2 (CM2) domains that co-assemble into a 2:2 complex in vitro. We solve the crystal structure of the LZ:CM2 complex, revealing that both proteins form helical dimers that assemble into an unusual tetramer. A slightly longer version of the LZ can form micron-scale structures with CM2, whose assembly is stimulated by Plk1 phosphorylation in vitro. Mutating individual residues that perturb LZ:CM2 tetramer assembly perturbs the formation of these micron-scale assemblies in vitro and Cnn-scaffold assembly in vivo. Thus, Cnn molecules have an intrinsic ability to form large, LZ:CM2-interaction-dependent assemblies that are critical for mitotic centrosome assembly. These studies provide the first atomic insight into a molecular interaction required for mitotic centrosome assembly.Z.F. and A.F.M.H. were supported by Sir William Dunn School EPA PhD studentships and also a Clarendon Scholarship and a Santander Graduate Award to A.F.M.H; A.C., A.W., M.A.C., P.T.C., and J.W.R. were supported by a Wellcome Trust Senior Investigator Award (104575); S.J. and S.M.L. were supported by a Wellcome Trust Senior Investigator Award (100298); A.W. was also partially supported by a Wellcome Trust Strategic Award to the Micron Oxford Advanced Bioimaging Unit (107457)

The discordance between clinical and radiographic knee osteoarthritis: A systematic search and summary of the literature

<p>Abstract</p> <p>Background</p> <p>Studies have suggested that the symptoms of knee osteoarthritis (OA) are rather weakly associated with radiographic findings and vice versa. Our objectives were to identify estimates of the prevalence of radiographic knee OA in adults with knee pain and of knee pain in adults with radiographic knee OA, and determine if the definitions of x ray osteoarthritis and symptoms, and variation in demographic factors influence these estimates.</p> <p>Methods</p> <p>A systematic literature search identifying population studies which combined x rays, diagnosis, clinical signs and symptoms in knee OA. Estimates of the prevalence of radiographic OA in people with knee pain were determined and vice versa. In addition the effects of influencing factors were scrutinised.</p> <p>Results</p> <p>The proportion of those with knee pain found to have radiographic osteoarthritis ranged from 15–76%, and in those with radiographic knee OA the proportion with pain ranged from 15% – 81%. Considerable variation occurred with x ray view, pain definition, OA grading and demographic factors</p> <p>Conclusion</p> <p>Knee pain is an imprecise marker of radiographic knee osteoarthritis but this depends on the extent of radiographic views used. Radiographic knee osteoarthritis is likewise an imprecise guide to the likelihood that knee pain or disability will be present. Both associations are affected by the definition of pain used and the nature of the study group. The results of knee x rays should not be used in isolation when assessing individual patients with knee pain.</p

Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation

This study was supported by the British Heart Foundation (PG 09/002/ 2642). AJR is funded by King’s College London British Heart Foundation Centre of Excellence and EI was supported by the Department of Health via National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s and St Tomas’ NHF Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. BG was supported by a British Heart Foundation studentship (FS/10/009/28166) and DC by an Arthritis Research UK Fellowship (18103)

Dose patterns in commercially insured subjects chronically exposed to opioids: a large cohort study in the United States

<p>Abstract</p> <p>Background</p> <p>Little data exist on how opioid doses vary with the length of exposure among chronic opioid users.</p> <p>Methods</p> <p>To characterize the change in the dosage of opioids over time, a retrospective cohort study using the PharMetrics database for the years 1999 through 2008 was conducted. Individuals exposed to opioids in 2000 who had 2 opioid dispensings at least 6 months apart and were opioid naive (did not receive any opioid 6 month before their exposure in 2000) were included. The date of the first dispensing in 2000 was defined as the index date and the dispensing had to be for a strong and full agonist opioid. All opioid doses were converted to oral morphine equivalent doses. Exposure was classified as continuous or intermittent. Mean, median, interquartile range, and 95^thpercentile of opioid dose over 6-month periods, as well as the percentage of subjects who ever received a high or very high opioid dose, were calculated.</p> <p>Results</p> <p>Among the 48,986 subjects, the mean age was 44.5 years and 54.5% were women. Intermittent exposure was observed in 99% of subjects; continuous exposure was observed in 1% of subjects. The mean duration of exposure for the subjects who were continuously exposed to opioids was 477 days. In subjects with no cancer diagnosis who were continuously exposed to opioids, the mean, 25^th, 50^th, and 75^thpercentile of dose was stable during the first 2 years of use, but the 95^thpercentile increased. Seven percent of them were exposed to doses of 180 mg or more of morphine at some point.</p> <p>Conclusions</p> <p>Dose escalation is uncommon in subjects with intermittent exposure to opioids. For subjects with continuous exposure to opioids who have cancer, doses rise substantially with time. For those without cancer, doses remain relatively stable for the first 2 years of use, but subsequently increase. Seven percent of subjects with no cancer diagnosis will be exposed to daily doses of 180 mg or more of morphine equivalent at some point.</p