Site-specific occurrence of nonmelanoma skin cancers in patients with cutaneous melanoma

In a registry-based case–control study, we compared the site-specific occurrence of nonmelanoma (keratinocytic) skin cancers among patients with cutaneous melanoma cases (cases, n=3774) and solid tumours (controls, n=349 923), respectively. Overall, patients with melanoma were almost five-fold more likely to develop keratinocytic cancers compared with solid tumour controls (adjusted OR 4.7, 95% CI 4.1–5.3), but the risks varied depending upon the site of melanoma. Whereas patients with melanoma of the head and neck had similarly increased risks of keratinocytic cancers across all body sites, patients with melanoma of the trunk were significantly more likely to develop keratinocyte cancer diagnosed on the trunk (adjusted OR 12.5, 95% CI 7.2–20.2) than on the head and neck (adjusted OR 3.0, 95% CI 2.2–4.3). Similar colocalisation of skin tumours was observed for patients with melanomas of the lower limb. These findings provide support for the hypothesis that skin cancers at different anatomical sites may arise through different causal pathways

Record linked retrospective cohort study of 4.6 million people exploring ethnic variations in disease: myocardial infarction in South Asians

Background Law and policy in several countries require health services to demonstrate that they are promoting racial/ethnic equality. However, suitable and accurate data are usually not available. We demonstrated, using acute myocardial infarction, that linkage techniques can be ethical and potentially useful for this purpose. Methods The linkage was based on probability matching. Encryption of a unique national health identifier (the Community Health Index (CHI)) ensured that information about health status and census-based ethnicity could not be ascribed to an identified individual. We linked information on individual ethnic group from the 2001 Census to Scottish hospital discharge and mortality data. Results Overall, 94% of the 4.9 million census records were matched to a CHI record with an estimated false positive rate of less than 0.1 %, with 84.9 – 87.6% of South Asians being successfully linked. Between April 2001 and December 2003 there were 126 first episodes of acute myocardial infarction (AMI) among South Asians and 30,978 among non-South Asians. The incidence rate ratio was 1.45 (95% CI 1.17, 1.78) for South Asian compared to non-South Asian men and 1.80 (95% CI 1.31, 2.48) for South Asian women. After adjustment for age, sex and any previous admission for diabetes the hazard ratio for death following AMI was 0.59 (95% CI 0.43, 0.81), reflecting better survival among South Asians. Conclusion The technique met ethical, professional and legal concerns about the linkage of census and health data and is transferable internationally wherever the census (or population register) contains ethnic group or race data. The outcome is a retrospective cohort study. Our results point to increased incidence rather than increased case fatality in explaining high CHD mortality rate. The findings open up new methods for researchers and health planners

Limited congruence exhibited across microbial, meiofaunal and macrofaunal benthic assemblages in a heterogeneous coastal environment

One of the most common approaches for investigating the ecology of spatially complex environments is to examine a single biotic assemblage present, such as macroinvertebrates. Underlying this approach are assumptions that sampled and unsampled taxa respond similarly to environmental gradients and exhibit congruence across different sites. These assumptions were tested for five benthic groups of various sizes (archaea, bacteria, microbial eukaryotes/protists, meiofauna and macrofauna) in Plymouth Sound, a harbour with many different pollution sources. Sediments varied in granulometry, hydrocarbon and trace metal concentrations. Following variable reduction, canonical correspondence analysis did not identify any associations between sediment characteristics and assemblage composition of archaea or macrofauna. In contrast, variation in bacteria was associated with granulometry, trace metal variations and bioturbation (e.g. community bioturbation potential). Protists varied with granulometry, hydrocarbon and trace metal predictors. Meiofaunal variation was associated with hydrocarbon and bioturbation predictors. Taxon turnover between sites varied with only three out of 10 group pairs showing congruence (meiofauna-protists, meiofauna-macrofauna and protists-macrofauna). While our results support using eukaryotic taxa as proxies for others, the lack of congruence suggests caution should be applied to inferring wider indicator or functional interpretations from studies of a single biotic assemblage

What punishment expresses

In this article, I consider the question of what punishment expresses and propose a way of approaching the question that overcomes problems in both psychosocial and philosophical expressivist traditions. The problem in both traditions is, I suggest, the need for an adequate moral – neither moralizing nor reductive – psychology, and I argue that Melanie Klein’s work offers such a moral psychology. I offer a reconstruction of Klein’s central claims and begin to sketch some of its potential implications for an expressive account of punishment. I outline a Kleinian interpretation of modern punishment’s expression as of an essentially persecutory nature but also include depressive realizations that have generally proved too difficult for liberal modernity to work through successfully, and the recent ‘persecutory turn’ is a defence against such realizations. I conclude by considering the wider philosophical significance of a Kleinian account for the expressivist theory of punishment

Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes

Effectiveness of individualized physiotherapy on pain and functioning compared to a standard exercise protocol in patients presenting with clinical signs of subacromial impingement syndrome. A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Shoulder impingement syndrome is a common musculoskeletal complaint leading to significant reduction of health and disability. Physiotherapy is often the first choice of treatment although its effectiveness is still under debate. Systematic reviews in this field highlight the need for more high quality trials to investigate the effectiveness of physiotherapy interventions in patients with subacromial impingement syndrome.</p> <p>Methods/Design</p> <p>This randomized controlled trial will investigate the effectiveness of individualized physiotherapy in patients presenting with clinical signs and symptoms of subacromial impingement, involving 90 participants aged 18-75. Participants are recruited from outpatient physiotherapy clinics, general practitioners, and orthopaedic surgeons in Germany. Eligible participants will be randomly allocated to either individualized physiotherapy or to a standard exercise protocol using central randomization.</p> <p>The control group will perform the standard exercise protocol aiming to restore muscular deficits in strength, mobility, and coordination of the rotator cuff and the shoulder girdle muscles to unload the subacromial space during active movements. Participants of the intervention group will perform the standard exercise protocol as a home program, and will additionally be treated with individualized physiotherapy based on clinical examination results, and guided by a decision tree. After the intervention phase both groups will continue their home program for another 7 weeks.</p> <p>Outcome will be measured at 5 weeks and at 3 and 12 months after inclusion using the shoulder pain and disability index and patients' global impression of change, the generic patient-specific scale, the average weekly pain score, and patient satisfaction with treatment. Additionally, the fear avoidance beliefs questionnaire, the pain catastrophizing scale, and patients' expectancies of treatment effect are assessed. Participants' adherence to the protocol, use of additional treatments for the shoulder, direct and indirect costs, and sick leave due to shoulder complaints will be recorded in a shoulder log-book.</p> <p>Discussion</p> <p>To our knowledge this is the first trial comparing individualized physiotherapy based on a defined decision making process to a standardized exercise protocol. Using high-quality methodologies, this trial will add evidence to the limited body of knowledge about the effect of physiotherapy in patients with SIS.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN86900354</p

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians

Aims/hypothesis: $FTO$ harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for $FTO$ in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the $FTO$ locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. Methods: All studies published on the association between $FTO$-rs9939609 (or proxy [r$^2$ > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. Results: The $FTO$-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10$^{−19}$), overweight by 1.13-fold/allele (p = 1.0 × 10$^{−11}$) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10$^{−8}$). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10$^{−5}$). The $FTO$-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10$^{−17}$), WHR by 0.003/allele (p = 1.2 × 10$^{−6}$), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of $FTO$ variation on obesity-related traits and type 2 diabetes was similar in the two populations. Conclusions/interpretation: $FTO$ is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, $FTO$ is also associated with type 2 diabetes independently of BMI. Electronic supplementary material The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users