Effect of population trends in body mass index on prostate cancer incidence and mortality in the United States.

Concurrent with increasing prostate cancer incidence and declining prostate cancer mortality in the United States, the prevalence of obesity has been increasing steadily. Several studies have reported that obesity is associated with increased risk of high-grade prostate cancer and prostate cancer mortality, and it is thus likely that the increase in obesity has increased the burden of prostate cancer. In this study, we assess the potential effect of increasing obesity on prostate cancer incidence and mortality. We first estimate obesity-associated relative risks of low- and high-grade prostate cancer using data from the Prostate Cancer Prevention Trial. Then, using obesity prevalence data from the National Health and Nutrition Examination Survey and prostate cancer incidence data from the Surveillance, Epidemiology, and End Results program, we convert annual grade-specific prostate cancer incidence rates into incidence rates conditional on weight category. Next, we combine the conditional incidence rates with the 1980 prevalence rates for each weight category to project annual grade-specific incidence under 1980 obesity levels. We use a simulation model based on observed survival and mortality data to translate the effects of obesity trends on prostate cancer incidence into effects on disease-specific mortality. The predicted increase in obesity prevalence since 1980 increased high-grade prostate cancer incidence by 15.5% and prostate cancer mortality by between 7.0% (under identical survival for obese and nonobese cases) and 23.0% (under different survival for obese and nonobese cases) in 2002. We conclude that increasing obesity prevalence since 1980 has partially obscured declines in prostate cancer mortality

Changes in human calcaneal morphology throughout the Pleistocene-Holocene Levant

The calcaneal morphology changed considerably during human evolution to enable efficient bipedal locomotion. However, little information exists regarding its adaptation to changes in habitual activities following the transition to a sedentary lifestyle. We aimed to examine changes in calcaneal morphology during the Pleistocene-Holocene Levant in light of sexual dimorphism. We studied three archaic Homo sapiens calcanei dated to the Middle and Upper Paleolithic, 23 Natufian hunter-gatherers, 12 Pre-Pottery Neolithic early farmers, and 31 Chalcolithic farmers. The calcanei were scanned via a surface scanner and measured, and bone proportions were calculated. Measurements included the height, length, and width of various calcaneal elements. The sex of each individual was determined using methods based on calcaneal morphology. The validity of these methods was tested in those individuals who had the pelvis (92.3% agreement rate). Accordingly, the sample included 59.4% males and 40.6% females. Most calcaneal indices were sex-independent, except for the relative width, relative anterior length, and the cuboid index. Temporal trends between the Natufian and Chalcolithic periods were more pronounced among males than females. While in the proximal calcaneus, the temporal trend was similar between males and females, it differed in the distal part and articular facets. The calcanei of archaic H. sapiens exceeded the average of the Natufian hunter-gatherer for most variables, though the trend varied. To conclude, males and females were affected differently by the changing environment. The calcanei of archaic H. sapiens were better adapted for activity involving high mobility, independent of sex. During the transition to a sedentary way of life, different factors probably designed the male and female calcaneus. These could include factors related to the sexual division of labor, adaptation to lengthy standing, and changes in footwear

Next-Generation Probiotics Targeting \u3ci\u3eClostridium difficile\u3c/i\u3e through Precursor- Directed Antimicrobial Biosynthesis

Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials

Developing understanding of pupil feedback using Habermas’ notion of communicative action

The focus of this article is to explore the notion of pupil feedback and the possible ways in which it can be understood and developed using Jürgen Habermas’ theory of Communicative Action. The theoretical position adopted is framed within the concept of assessment for learning, and is particularly related to the notion of assessment as learning within AfL. Furthermore, the paper is located within a social constructivist perspective. Jürgen Habermas’ theory of Communicative Action enables us to recognise that feedback, and more importantly the interpretation of feedback, cannot be a one-way process. Without recognition of pupil interpretation, its very purpose (to alter the learning gap) is compromised. This paper offers new ways of exploring feedback, which recognise complexity and the importance of interpretation and relationships in shared negotiated communicative contexts. It further contributes to the ways in which assessment and learning are understood and intersect

Assessment as learning: Blurring the boundaries of assessment and learning for theory, policy and practice

This paper explores assessment and learning in a way that blurs their boundaries. The notion of assessment as learning (AaL) is offered as an aspect of formative assessment (assessment for learning). It considers how pupils self-regulate their own learning, and in so doing make complex decisions about how they use feedback and engage with the learning priorities of the classroom. Discussion is framed from a sociocultural stance, yet challenges some of the perspectives that have widely become accepted. It offers three new views to help explore the concept of AaL: understanding feedback; understanding the learning gap; and exploring vocabularies of assessment. Pragmatically, the ideas examined suggest that teachers may need to consider less about focused and directive feedback, but more about how learners interpret and understand feedback from their self-regulatory and self-productive identities and how vocabularies for assessment can be more collaboratively shared in learning contexts. © 2014 © 2014 Taylor & Francis

Genetic Polymorphisms in the Hypothalamic Pathway in Relation to Subsequent Weight Change – The DiOGenes Study

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects. AIM: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake. METHODS AND FINDINGS: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻⁷). CONCLUSIONS: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation

Felony Murder and Capital Punishment: an Examination of the Deterrence Question

A proper test of the deterrent effect of the death penalty must consider capital homicides. However, the criterion variable in most investigations has been total homicides—most of which bear no legal or theoretical relationship to capital punishment. To address this fundamental data problem, this investigation used Federal Bureau of Investigation data for 1976–1987 to examine the relationship between capital punishment and felony murder, the most common type of capital homicide. We conducted time series analyses of monthly felony murder rates, the frequency of executions, and the amount and type of television coverage of executions over the period. The analyses revealed occasional departures (for vehicle theft and narcotics killings) from the null hypotheses. However, on balance, and in line with the vast majority of capital punishment studies, this investigation found no consistent evidence that executions and the television coverage they receive are associated significantly with rates for total, index, or different types of felony murder

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements