Ironing out sex differences in tuberculosis prevalence

Last year, two striking studies focused attention on sex differences in tuberculosis (TB) epidemiology. Katherine Horton and team’s metaanalysis of 56 prevalence surveys undertaken in low- and middle-income countries found that adult men had 2.21 (95% CI, 1.92–2.54) times more bacteriologically confirmed TB than adult women. The equivalent ratio for smear-positive TB (reported in 40 surveys), was 2.51 (95%CI 2.07–3.04). A male preponderance of prevalent TB was observed in all World Health Organization geographical regions that contributed sufficient data to draw meaningful conclusions. In the second study, Pete Dodd and colleagues utilised data on adult TB prevalence, the incidence of Mycobacterium tuberculosis infection in children, and data on social contact patterns from communities in Zambia and the Western Cape of South Africa, to produce modelled estimates of the incidence of M. tuberculosis infection, by age and sex. Whilst men and women had similar numbers of social contacts, contact patterns were strongly age and sex assortative. A key finding was that 66% (95%CI 64–67, Zambia) and 57% (95%CI 56–58, Western Cape) of incident M. tuberculosis infections were attributable to contact with adult men. The authors commented that this ‘was largely because tuberculosis prevalence was higher in male interviewees’

A Fast Algorithm for Robust Regression with Penalised Trimmed Squares

The presence of groups containing high leverage outliers makes linear regression a difficult problem due to the masking effect. The available high breakdown estimators based on Least Trimmed Squares often do not succeed in detecting masked high leverage outliers in finite samples. An alternative to the LTS estimator, called Penalised Trimmed Squares (PTS) estimator, was introduced by the authors in \cite{ZiouAv:05,ZiAvPi:07} and it appears to be less sensitive to the masking problem. This estimator is defined by a Quadratic Mixed Integer Programming (QMIP) problem, where in the objective function a penalty cost for each observation is included which serves as an upper bound on the residual error for any feasible regression line. Since the PTS does not require presetting the number of outliers to delete from the data set, it has better efficiency with respect to other estimators. However, due to the high computational complexity of the resulting QMIP problem, exact solutions for moderately large regression problems is infeasible. In this paper we further establish the theoretical properties of the PTS estimator, such as high breakdown and efficiency, and propose an approximate algorithm called Fast-PTS to compute the PTS estimator for large data sets efficiently. Extensive computational experiments on sets of benchmark instances with varying degrees of outlier contamination, indicate that the proposed algorithm performs well in identifying groups of high leverage outliers in reasonable computational time.Comment: 27 page

‘Bring back Hitler’s gas chambers’: asylum seeking, Nazis and facebook – a discursive analysis

In this article, we explore how talk about Nazis is used in Internet discussions regarding asylum seeking, and the issue of whether or not opposition to asylum seeking is racist. Discursive analysis was conducted on discussions about asylum seeking from the social networking website Facebook, where references to Nazis were made. Three strategies were identified: (1) people supporting asylum seeking accuse asylum opponents of being racist by referring to Nazis; (2) opponents of asylum seeking deal with such accusations by arguing that the debate is being suppressed because of references to Nazis; (3) in the final, and most striking, strategy, opponents of asylum draw upon ideas associated with the Nazis and Hitler to bring about their anti-asylum position. These findings are discussed in relation to how the link between Nazis and racism is emerging in the asylum debat

Flexible Meta-Regression to Assess the Shape of the Benzene–Leukemia Exposure–Response Curve

Ba c k g r o u n d: Previous evaluations of the shape of the benzene–leukemia exposure–response curve (ERC) were based on a single set or on small sets of human occupational studies. Integrating evidence from all available studies that are of sufficient quality combined with flexible meta-regression models is likely to provide better insight into the functional relation between benzene exposure and risk of leukemia. Objectives: We used natural splines in a flexible meta-regression method to assess the shape of the benzene–leukemia ERC. Met h o d s: We fitted meta-regression models to 30 aggregated risk estimates extracted from nine human observational studies and performed sensitivity analyses to assess the impact of a priori assessed study characteristics on the predicted ERC. Re s u l t s: The natural spline showed a supralinear shape at cumulative exposures less than 100 ppmyears, although this model fitted the data only marginally better than a linear model (p = 0.06). Stratification based on study design and jackknifing indicated that the cohort studies had a considerable impact on the shape of the ERC at high exposure levels (> 100 ppm-years) but that predicted risks for the low exposure range (< 50 ppm-years) were robust. Co n c l u s i o n s: Although limited by the small number of studies and the large heterogeneity between studies, the inclusion of all studies of sufficient quality combined with a flexible meta-regression method provides the most comprehensive evaluation of the benzene–leukemia ERC to date. The natural spline based on all data indicates a significantly increased risk of leukemia [relative risk (RR) = 1.14; 95 % confidence interval (CI), 1.04–1.26] at an exposure level as low as 10 ppm-years. Key w o r d s: benzene, epidemiology, leukemia, meta-regression, quantitative risk assessment. Environ Health Perspect 118:526–532 (2010). doi:10.1289/ehp.0901127 available vi

Sal-type ABC-F proteins: intrinsic and common mediators of pleuromutilin resistance by target protection in staphylococci

The first member of the pleuromutilin (PLM) class suitable for systemic antibacterial chemotherapy in humans recently entered clinical use, underscoring the need to better understand mechanisms of PLM resistance in disease-causing bacterial genera. Of the proteins reported to mediate PLM resistance in staphylococci, the least-well studied to date is Sal(A), a putative ABC-F NTPase that—by analogy to other proteins of this type—may act to protect the ribosome from PLMs. Here, we establish the importance of Sal proteins as a common source of PLM resistance across multiple species of staphylococci. Sal(A) is revealed as but one member of a larger group of Sal-type ABC-F proteins that vary considerably in their ability to mediate resistance to PLMs and other antibiotics. We find that specific sal genes are intrinsic to particular staphylococcal species, and show that this gene family is likely ancestral to the genus Staphylococcus. Finally, we solve the cryo-EM structure of a representative Sal-type protein (Sal(B)) in complex with the staphylococcal 70S ribosome, revealing that Sal-type proteins bind into the E site to mediate target protection, likely by displacing PLMs and other antibiotics via an allosteric mechanism

Brief Report: AIP Mutation in Pituitary Adenomas in the 18th Century and Today

From New England Journal of Medicine, Volume 364, issue 1, p.43-50. Copyright © (2011) Massachusetts Medical Society. Reprinted with permission.Gigantism results when a growth hormone–secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783,1-3 he noted an enlarged pituitary fossa. We extracted DNA from the patient’s teeth and identified a germline mutation in the aryl hydrocarbon–interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier

Getting into hot water:sick guppies frequent warmer thermal conditions

Ectotherms depend on the environmental temperature for thermoregulation and exploit thermal regimes that optimise physiological functioning. They may also frequent warmer conditions to up-regulate their immune response against parasite infection and/or impede parasite development. This adaptive response, known as ‘behavioural fever’, has been documented in various taxa including insects, reptiles and fish, but only in response to endoparasite infections. Here, a choice chamber experiment was used to investigate the thermal preferences of a tropical freshwater fish, the Trinidadian guppy (Poecilia reticulata), when infected with a common helminth ectoparasite Gyrodactylus turnbulli, in female-only and mixed-sex shoals. The temperature tolerance of G. turnbulli was also investigated by monitoring parasite population trajectories on guppies maintained at a continuous 18, 24 or 32 °C. Regardless of shoal composition, infected fish frequented the 32 °C choice chamber more often than when uninfected, significantly increasing their mean temperature preference. Parasites maintained continuously at 32 °C decreased to extinction within 3 days, whereas mean parasite abundance increased on hosts incubated at 18 and 24 °C. We show for the first time that gyrodactylid-infected fish have a preference for warmer waters and speculate that sick fish exploit the upper thermal tolerances of their parasites to self medicate

Noninvasive diffusion magnetic resonance imaging of brain tumour cell size for the early detection of therapeutic response

Cancer cells differ in size from those of their host tissue and are known to change in size during the processes of cell death. A noninvasive method for monitoring cell size would be highly advantageous as a potential biomarker of malignancy and early therapeutic response. This need is particularly acute in brain tumours where biopsy is a highly invasive procedure. Here, diffusion MRI data were acquired in a GL261 glioma mouse model before and during treatment with Temozolomide. The biophysical model VERDICT (Vascular Extracellular and Restricted Diffusion for Cytometry in Tumours) was applied to the MRI data to quantify multi-compartmental parameters connected to the underlying tissue microstructure, which could potentially be useful clinical biomarkers. These parameters were compared to ADC and kurtosis diffusion models, and, measures from histology and optical projection tomography. MRI data was also acquired in patients to assess the feasibility of applying VERDICT in a range of different glioma subtypes. In the GL261 gliomas, cellular changes were detected according to the VERDICT model in advance of gross tumour volume changes as well as ADC and kurtosis models. VERDICT parameters in glioblastoma patients were most consistent with the GL261 mouse model, whilst displaying additional regions of localised tissue heterogeneity. The present VERDICT model was less appropriate for modelling more diffuse astrocytomas and oligodendrogliomas, but could be tuned to improve the representation of these tumour types. Biophysical modelling of the diffusion MRI signal permits monitoring of brain tumours without invasive intervention. VERDICT responds to microstructural changes induced by chemotherapy, is feasible within clinical scan times and could provide useful biomarkers of treatment response

Caffeine Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

Purpose: To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. Methods: Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg 21; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo ingestion (PMPLAC trial). A randomized, doubleblind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ) and bench press (BP) exercises against loads that elicit maximum strength (75 % 1RM load) and muscle power adaptations (1 m s 21 load). Isometric maximum voluntary contraction (MVCLEG) and isometric electrically evoked strength of the right knee (EVOK LEG) were measured to identify caffeine’s action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone) were evaluated at the beginning of each trial (PRE). In addition, plasma norepinephrine (NE) and epinephrine were measured PRE and at the end of each trial following a standardized intense (85 % 1RM) 6 repetitions bout of SQ (POST). Results: In the PM PLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AM PLA