Hookworm Infection and Environmental Factors in Mbeya Region, Tanzania: A Cross-sectional, Population-based study.

Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics. Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control. Cross-sectional interview data and stool samples from 6,375 participants from nine different sites in Mbeya region, south-western Tanzania, were collected as part of a cohort study. Hookworm infection was assessed by microscopy of duplicate Kato-Katz thick smears from one stool sample from each participant. A geographic information system was used to obtain remotely sensed environmental data such as land surface temperature (LST), vegetation cover, rainfall, and elevation, and combine them with hookworm infection data and with socio-demographic and behavioral data. Uni- and multivariable logistic regression was performed on sites separately and on the pooled dataset. Univariable analyses yielded significant associations for all ecological variables. Five ecological variables stayed significant in the final multivariable model: population density (odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.63-0.73), mean annual vegetation density (OR = 0.11; 95% CI = 0.06-0.18), mean annual LST during the day (OR = 0.81; 95% CI = 0.75-0.88), mean annual LST during the night (OR = 1.54; 95% CI = 1.44-1.64), and latrine coverage in household surroundings (OR = 1.02; 95% CI = 1.01-1.04). Interaction terms revealed substantial differences in associations of hookworm infection with population density, mean annual enhanced vegetation index, and latrine coverage between the two sites with the highest prevalence of infection. This study supports previous findings that remotely sensed data such as vegetation indices, LST, and elevation are strongly associated with hookworm prevalence. However, the results indicate that the influence of environmental conditions can differ substantially within a relatively small geographic area. The use of large-scale associations as a predictive tool on smaller scales is therefore problematic and should be handled with care

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

Scaling Patterns for QCD Jets

Jet emission at hadron colliders follows simple scaling patterns. Based on perturbative QCD we derive Poisson and staircase scaling for final state as well as initial state radiation. Parton density effects enhance staircase scaling at low multiplicities. We propose experimental tests of our theoretical findings in Z+jets and QCD gap jets production based on minor additions to current LHC analyses.Comment: 36 pages, 16 figure

Residential Radon and Brain Tumour Incidence in a Danish Cohort

BACKGROUND: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. OBJECTIVE: To investigate the long-term effect of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. METHODS: During 1993-1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced residential addresses from 1 January 1971 until 31 December 2009 and calculated radon concentrations at each address using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and 95% confidence intervals (CI) for the risk of primary brain tumours associated with residential radon exposure with adjustment for age, sex, occupation, fruit and vegetable consumption and traffic-related air pollution. Effect modification by air pollution was assessed. RESULTS: Median estimated radon was 40.5 Bq/m(3). The adjusted IRR for primary brain tumour associated with each 100 Bq/m(3) increment in average residential radon levels was 1.96 (95% CI: 1.07; 3.58) and this was exposure-dependently higher over the four radon exposure quartiles. This association was not modified by air pollution. CONCLUSIONS: We found significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies

Environment change, economy change and reducing conflict at source

At a time when fossil fuel burning, nationalism, ethnic and religious intolerance, and other retrograde steps are being promoted, the prospects for world peace and environmental systems stability may appear dim. Yet now is it the more important to continue to examine the sources of conflict. A major obstacle to general progress is the currently dominant economic practice and theory, which is here called the economy-as-usual, or economics-as-usual, as appropriate. A special obstacle to constructive change is the language in which economic matters are usually discussed. This language is narrow, conservative, technical and often obscure. The rapid changes in the environment (physical and living) are largely kept in a separate compartment. If, however, the partition is removed, economics -as-usual, with its dependence on growth and its widening inequality, is seen to be unsustainable. Radical economic change, for better or worse, is to be expected. Such change is here called economy change. The change could be for the better if it involved an expansion of the concept of economics itself, along the lines of oikonomia, a modern revival of a classical Greek term for management or household. In such an expanded view, not everything of economic value can be measured. It is argued that economics-as-usual is the source of much strife. Some features are indicated of a less conflictual economy - more just, cooperative and peaceful. These features include a dignified life available to all people as of right, the word 'wealth' being reconnected with weal, well and well-being, and 'work' being understood as including all useful activity

The feasibility of an exercise intervention in males at risk of oesophageal adenocarcinoma: a randomized controlled trial

Objective: To investigate the feasibility and safety of a 24-week exercise intervention, compared to control, in males with Barrett's oesophagus, and to estimate the effect of the intervention, compared to control, on risk factors associated with oesophageal adenocarcinoma development. Methods: A randomized controlled trial of an exercise intervention (60 minutes moderate-intensity aerobic and resistance exercise five days/week over 24 weeks; one supervised and four unsupervised sessions) versus attention control (45 minutes stretching five days/week over 24 weeks; one supervised and four unsupervised sessions) in inactive, overweight/obese (25.0-34.9 kg/m2) males with Barrett's oesophagus, aged 18-70 years. Primary outcomes were obesity-associated hormones relevant to oesophageal adenocarcinoma risk (circulating concentrations of leptin, adiponectin, interleukin-6, tumour necrosis factor-alpha, C-reactive protein, and insulin resistance HOMA). Secondary outcomes included waist circumference, body composition, fitness, strength and gastro-oesophageal reflux symptoms. Outcomes were measured at baseline and 24-weeks. Intervention effects were analysed using generalised linear models, adjusting for baseline value. Results: Recruitment was difficult in this population with a total of 33 participants recruited (target sample size: n = 80); 97% retention at 24-weeks. Adherence to the exercise protocol was moderate. No serious adverse events were reported. A statistically significant intervention effect (exercise minus control) was observed for waist circumference (-4.5 95%CI -7.5, -1.4 cm; p < 0.01). Effects on primary outcomes were not statistically significant. Conclusion: This small, exploratory trial provides important information to inform future trial development including recruitment rates and estimates of effect sizes on outcomes related to oesophageal adenocarcinoma risk. Future trials should investigate a combined dietary and exercise intervention to achieve greater weight loss in this population and relax inclusion criteria to maximize recruitment. Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000401257. © 2015 Winzer et al

Phenotypic variation and fitness in a metapopulation of tubeworms (Ridgeia piscesae Jones) at hydrothermal vents

We examine the nature of variation in a hot vent tubeworm, Ridgeia piscesae, to determine how phenotypes are maintained and how reproductive potential is dictated by habitat. This foundation species at northeast Pacific hydrothermal sites occupies a wide habitat range in a highly heterogeneous environment. Where fluids supply high levels of dissolved sulphide for symbionts, the worm grows rapidly in a ‘‘short-fat’’ phenotype characterized by lush gill plumes; when plumes are healthy, sperm package capture is higher. This form can mature within months and has a high fecundity with continuous gamete output and a lifespan of about three years in unstable conditions. Other phenotypes occupy low fluid flux habitats that are more stable and individuals grow very slowly; however, they have low reproductive readiness that is hampered further by small, predator cropped branchiae, thus reducing fertilization and metabolite uptake. Although only the largest worms were measured, only 17% of low flux worms were reproductively competent compared to 91% of high flux worms. A model of reproductive readiness illustrates that tube diameter is a good predictor of reproductive output and that few low flux worms reached critical reproductive size. We postulate that most of the propagules for the vent fields originate from the larger tubeworms that live in small, unstable habitat patches. The large expanses of worms in more stable low flux habitat sustain a small, but long-term, reproductive output. Phenotypic variation is an adaptation that fosters both morphological and physiological responses to differences in chemical milieu and predator pressure. This foundation species forms a metapopulation with variable growth characteristics in a heterogeneous environment where a strategy of phenotypic variation bestows an advantage over specialization

Transcriptional Reprogramming of CD11b+Esamhi Dendritic Cell Identity and Function by Loss of Runx3

Classical dendritic cells (cDC) are specialized antigen-presenting cells mediating immunity and tolerance. cDC cell-lineage decisions are largely controlled by transcriptional factor regulatory cascades. Using an in vivo cell-specific targeting of Runx3 at various stages of DC lineage development we show that Runx3 is required for cell-identity, homeostasis and function of splenic Esamhi DC. Ablation of Runx3 in DC progenitors led to a substantial decrease in splenic CD4+/CD11b+ DC. Combined chromatin immunoprecipitation sequencing and gene expression analysis of purified DC-subsets revealed that Runx3 is a key gene expression regulator that facilitates specification and homeostasis of CD11b+Esamhi DC. Mechanistically, loss of Runx3 alters Esamhi DC gene expression to a signature characteristic of WT Esamlow DC. This transcriptional reprogramming caused a cellular change that diminished phagocytosis and hampered Runx3-/- Esamhi DC capacity to prime CD4+ T cells, attesting to the significant role of Runx3 in specifying Esamhi DC identity and function

Tight coupling of leaf area index to canopy nitrogen and phosphorus across heterogeneous tallgrass prairie communities

Nitrogen (N) and phosphorus (P) are limiting nutrients for many plant communities worldwide. Foliar N and P along with leaf area are among the most important controls on photosynthesis and hence productivity. However, foliar N and P are typically assessed as species level traits, whereas productivity is often measured at the community scale. Here, we compared the community-level traits of leaf area index (LAI) to total foliar nitrogen (TFN) and total foliar phosphorus (TFP) across nearly three orders of magnitude LAI in grazed and ungrazed tallgrass prairie in north-eastern Kansas, USA. LAI was strongly correlated with both TFN and TFP across communities, and also within plant functional types (grass, forb, woody, and sedge) and grazing treatments (bison or cattle, and ungrazed). Across almost the entire range of LAI values and contrasting communities, TFN:TFP ratios indicated co-limitation by N and P in almost all communities; this may further indicate a community scale trend of an optimal N and P allocation per unit leaf area for growth. Previously, results from the arctic showed similar tight relationships between LAI:TFN, suggesting N is supplied to canopies to maximize photosynthesis per unit leaf area. This tight coupling between LAI, N, and P in tallgrass prairie suggests a process of optimal allocation of N and P, wherein LAI remains similarly constrained by N and P despite differences in species composition, grazing, and canopy density

mTOR: from growth signal integration to cancer, diabetes and ageing

In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.National Institutes of Health (U.S.)Howard Hughes Medical InstituteWhitehead Institute for Biomedical ResearchJane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France