Hyporheic Zone Microbiome Assembly Is Linked to Dynamic Water Mixing Patterns in Snowmelt-Dominated Headwater Catchments

Terrestrial and aquatic elemental cycles are tightly linked in upland fluvial networks. Biotic and abiotic mineral weathering, microbially mediated degradation of organic matter, and anthropogenic influences all result in the movement of solutes (e.g., carbon, metals, and nutrients) through these catchments, with implications for downstream water quality. Within the river channel, the region of hyporheic mixing represents a hot spot of microbial activity, exerting significant control over solute cycling. To investigate how snowmelt-driven seasonal changes in river discharge affect microbial community assembly and carbon biogeochemistry, depth-resolved pore water samples were recovered from multiple locations around a representative meander on the East River near Crested Butte, CO, USA. Vertical temperature sensor arrays were also installed in the streambed to enable seepage flux estimates. Snowmelt-driven high river discharge led to an expanding zone of vertical hyporheic mixing and introduced dissolved oxygen into the streambed that stimulated aerobic microbial respiration. These physicochemical processes contributed to microbial communities undergoing homogenizing selection, in contrast to other ecosystems where lower permeability may limit the extent of mixing. Conversely, lower river discharge conditions led to a greater influence of upwelling groundwater within the streambed and a decrease in microbial respiration rates. Associated with these processes, microbial communities throughout the streambed exhibited increasing dissimilarity between each other, suggesting that the earlier onset of snowmelt and longer periods of base flow may lead to changes in the composition (and associated function) of streambed microbiomes, with consequent implications for the processing and export of solutes from upland catchments

Prevalence and Correlates of Common Mental Disorders among Mothers of Young Children in Kilimanjaro Region of Tanzania.

Although poor maternal mental health is a major public health problem, with detrimental effects on the individual, her children and society, information on its correlates in low-income countries is sparse. This study investigates the prevalence of common mental disorders (CMD) among at-risk mothers, and explores its associations with sociodemographic factors. This population-based survey of mothers of children aged 0-36 months used the 14-item Shona Symptom Questionnaire (SSQ). Mothers whose response was "yes" to 8 or more items on the scale were defined as "at risk of CMD." Of the 1,922 mothers (15-48 years), 28.8% were at risk of CMD. Risk of CMD was associated with verbal abuse, physical abuse, a partner who did not help with the care of the child, being in a polygamous relationship, a partner with low levels of education, and a partner who smoked cigarettes. Cohabiting appeared to be protective. Taken together, our results indicate the significance of the quality of relations with one's partner in shaping maternal mental health. The high proportion of mothers who are at risk of CMD emphasizes the importance of developing evidence-based mental health programmes as part of the care package aimed at improving maternal well-being in Tanzania and other similar settings

Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution

Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.This work was supported by a PhD studentship funded by QMUL and awarded to D.C.S. and a Leverhulme Trust grant (RPG- 2013-351) awarded to M.R.E. Sequencing of the A. rubens neural transcriptome was funded by an EPSRC grant (EP/J501360/1

Evaluation of α2-Integrin Expression as a Biomarker for Tumor Growth Inhibition for the Investigational Integrin Inhibitor E7820 in Preclinical and Clinical Studies

E7820 is an orally active inhibitor of α2-integrin mRNA expression, currently tested in phases I and II. We aimed to evaluate what levels of inhibition of integrin expression are needed to achieve tumor stasis in mice, and to compare this to the level of inhibition achieved in humans. Tumor growth inhibition was measured in mice bearing a pancreatic KP-1 tumor, dosed at 12.5–200 mg/kg over 21 days. In the phase I study, E7820 was administered daily for 28 days over a range of 0–200 mg, followed by a 7-day washout period. PK-PD models were developed in NONMEM. α2-Integrin expression measured on platelets, corresponding to tumor stasis at t = 21 in 50% and 90% of the mice (Iint,50, Iint,90) were calculated. It was evaluated if these levels of inhibition could be achieved in patients at tolerable doses. One hundred nineteen α2-Integrin measurements and 210 tumor size measurements were available from mice. The relationship between PK and α2-integrin expression was modeled using an indirect-effect model, subsequently linked to an exponential tumor growth model. Iinh,50 and Iinh,90 were 14.7% (RSE 7%) and 17.9% (RSE 8%). Four hundred sixty two α2-integrin measurements were available from 29 patients. Using the schedule of 100 mg qd (MTD), α2-integrin expression was inhibited more strongly than the Iint,50 and Iint,90 in greater than 95% and greater than 50% of patients, respectively. Moderate inhibition of α2-integrin expression corresponded to tumor stasis in mice, and similar levels could be reached in patients with the dose level of 100 mg qd

Rethinking the patient: using Burden of Treatment Theory to understand the changing dynamics of illness

<b>Background</b> In this article we outline Burden of Treatment Theory, a new model of the relationship between sick people, their social networks, and healthcare services. Health services face the challenge of growing populations with long-term and life-limiting conditions, they have responded to this by delegating to sick people and their networks routine work aimed at managing symptoms, and at retarding - and sometimes preventing - disease progression. This is the new proactive work of patient-hood for which patients are increasingly accountable: founded on ideas about self-care, self-empowerment, and self-actualization, and on new technologies and treatment modalities which can be shifted from the clinic into the community. These place new demands on sick people, which they may experience as burdens of treatment.<p></p> <b>Discussion</b> As the burdens accumulate some patients are overwhelmed, and the consequences are likely to be poor healthcare outcomes for individual patients, increasing strain on caregivers, and rising demand and costs of healthcare services. In the face of these challenges we need to better understand the resources that patients draw upon as they respond to the demands of both burdens of illness and burdens of treatment, and the ways that resources interact with healthcare utilization.<p></p> <b>Summary</b> Burden of Treatment Theory is oriented to understanding how capacity for action interacts with the work that stems from healthcare. Burden of Treatment Theory is a structural model that focuses on the work that patients and their networks do. It thus helps us understand variations in healthcare utilization and adherence in different healthcare settings and clinical contexts

Mechanical compression attenuates normal human bronchial epithelial wound healing

Background: Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. Methods: Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1) unperturbed control cells, 2) single scrape wound only, 3) static compression (6 hours of 30 cmH(2)O), and 4) 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. Results: We found that mechanical compression and scrape injury increase TGF-beta 2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE(2) media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE(2), but not EGF. Conclusion: Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE(2) and a compromised cytoskeleton

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

A systematic review of adolescent physiological development and its relationship with health-related behaviour:a protocol

BACKGROUND: At any one time, there are one billion people worldwide who are in the second decade of their life, and 1.8 billion in the 10–24 age range. Whilst a great deal of focus has been placed on healthy early years development, the adolescent years are also a unique period of opportunity: exposure to health-influencing behaviours such as alcohol consumption or cigarette smoking, may serve to establish patterns that have significant health consequences in later life. Although there is often an emphasis on risk-taking and detrimental health behaviours during adolescence, these years also provide significant opportunities for behaviour to be shaped in positive ways that may improve longer term health outcomes. However, it is firstly important to understand the complex physiological changes that are taking place within the human body during this period and their relationship with health-related behaviour. Such knowledge can help to inform health policy and intervention development. AIM: The aim of this study is to gain a comprehensive understanding of the relationship between physiological development and health-related behaviours in adolescence. METHODS: The principles of an integrative review will be used. Such reviews are of use where research has emerged in different fields, to combine existing knowledge and produce a more extensive understanding. Studies from a range of different methodological approaches, published or unpublished, will be included. A range of databases and literature depositories will be searched using a pre-defined search strategy. The review will include studies that focus on adolescents (nominally, those aged 10–24 years). We will seek papers that focus on both physiological development and health behaviour, or papers focusing solely on physiological development if there are clear implications for health behaviour. Studies with a focus on participants with specific health conditions will be excluded. Two reviewers will independently screen potential studies for eligibility and quality; members of the project team will act as third reviewers in the case of uncertainty or discrepancy. Further analyses (e.g. meta-analysis, meta-synthesis, meta-summary) will be decided upon, and sub-set analyses carried out. Finally, an integrative summation will be produced, giving a critical analysis of the results and providing conclusions and recommendations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-015-0173-5) contains supplementary material, which is available to authorized users