Numerical simulation of spring hydrograph recession curves for evaluating behavior of the East Yorkshire chalk aquifer

The Cretaceous Chalk aquifer is the most important in the UK for the provision of water to public supply and agriculture. The Chalk has both matrix and fracture porosity and is thus best considered as a dual porosity aquifer system. Although the matrix porosity is large, typically around 0.35 in the study area of East Yorkshire, UK (ESI, 2010), pore diameters are typically very small, and the water contained in them is virtually immobile. The high permeability fracture network is responsible for the ability of water to drain; spatial variations in fracture network properties mean conventional approaches to aquifer characterization such as borehole pumping tests are of limited utility. Hence this study attempts to better understand the flow system and characterise aquifer properties from the recession response seen at springs during the spring/summer period when recharge is minimal. This approach has the advantage that spring hydrographs represent the sum of the response from entire catchments. This paper reports numerical modeling for simulating aquifer and spring responses during hydrological recession. Firstly, available geological and hydrogeological information for the study area was used to develop hydrogeological conceptual models. Four different numerical models have been constructed representing four possible scenarios that could represent the aquifer in the selected area. These are: single reservoir aquifer, double reservoir aquifer, single reservoir aquifer with highly permeable vertical zone intersecting the spring location and single reservoir aquifer containing tunnel shaped highly permeable zone at the spring elevation respectively. The sensitivity of spring recession response to various external and internal parameter values was investigated, to understand relations between spring recession, hydrological inputs (recharge) and aquifer structure. Spring hydrographs from the real aquifer were compared with the hydrographs generated from models, in order to estimate aquifer properties. The work aims to identify the utility of spring hydrographs in eliciting aquifer permeability structure, as well as identifying the conceptual scenario which best represents the Chalk Aquifer in East Yorkshire, UK

‘Warning: allergic to penicillin’: association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes

Background The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. Objectives To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. Methods We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. Results PenA prevalence was 5.9% (IQR = 3.8%–8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. Conclusions PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes

Scanning-probe spectroscopy of semiconductor donor molecules

Semiconductor devices continue to press into the nanoscale regime, and new applications have emerged for which the quantum properties of dopant atoms act as the functional part of the device, underscoring the necessity to probe the quantum structure of small numbers of dopant atoms in semiconductors[1-3]. Although dopant properties are well-understood with respect to bulk semiconductors, new questions arise in nanosystems. For example, the quantum energy levels of dopants will be affected by the proximity of nanometer-scale electrodes. Moreover, because shallow donors and acceptors are analogous to hydrogen atoms, experiments on small numbers of dopants have the potential to be a testing ground for fundamental questions of atomic and molecular physics, such as the maximum negative ionization of a molecule with a given number of positive ions[4,5]. Electron tunneling spectroscopy through isolated dopants has been observed in transport studies[6,7]. In addition, Geim and coworkers identified resonances due to two closely spaced donors, effectively forming donor molecules[8]. Here we present capacitance spectroscopy measurements of silicon donors in a gallium-arsenide heterostructure using a scanning probe technique[9,10]. In contrast to the work of Geim et al., our data show discernible peaks attributed to successive electrons entering the molecules. Hence this work represents the first addition spectrum measurement of dopant molecules. More generally, to the best of our knowledge, this study is the first example of single-electron capacitance spectroscopy performed directly with a scanning probe tip[9].Comment: In press, Nature Physics. Original manuscript posted here; 16 pages, 3 figures, 5 supplementary figure

A new version of the HBSC Family Affluence Scale - FAS III: Scottish qualitative findings from the International FAS Development Study

A critical review of the Family Affluence Scale (FAS) concluded that FAS II was no longer discriminatory within very rich or very poor countries, where a very high or a very low proportion of children were categorised as high FAS or low FAS respectively (Currie et al. 2008). The review concluded that a new version of FAS - FAS III - should be developed to take into account current trends in family consumption patterns across the European region, the US and Canada. In 2012, the FAS Development and Validation Study was conducted in eight countries - Denmark, Greenland, Italy, Norway, Poland, Romania, Slovakia and Scotland. This paper describes the Scottish qualitative findings from this study. The Scottish qualitative fieldwork comprising cognitive interviews and focus groups sampled from 11, 13 and 15 year-old participants from 18 of the most- and least- economically deprived schools. These qualitative results were used to inform the final FAS III recommendations.Publisher PDFPeer reviewe

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

Do 'good values' lead to 'good' health-behaviours? Longitudinal associations between young people's values and later substance-use

<p>Background: Past studies have linked certain values (traditional vs. individualistic) with adolescent substance-use. The aims of this study are to replicate cross-sectional research linking values and adolescent substance-use and to determine if such values predict future substance-use.</p> <p>Methods: A longitudinal school-based survey of 2196 young people (age 15) followed up in early adulthood (age 18/19). Participants provided data about their beliefs and values at age 15, and their substance-use (smoking, alcohol and drug-use) at ages 15 and 18/19. In addition data were collected about their social background (gender, risk-taking, deprivation, religion, etc).</p> <p>Results: Cross-sectionally, young people with anti-authority values were more likely to use various substances, e.g. 17-67% more likely to regularly smoke (daily), drink (most days), or use drugs (weekly) for each SD above typical levels. Adjusting for social background, associations were not substantially attenuated. However in the prospective analysis, adjusting for both background and substance-use at age 15, only two (anti-authoritarian and work ethic) values were (marginally) associated with substance-use at age 18/19.</p> <p>Conclusions: While we replicated results found in prior cross-sectional studies, evidence from this study does not support the argument that holding certain 'pro-social' or 'good' values substantively protects against later substance-use and challenges the likely effectiveness of values-based interventions in relation to later substance-use.</p&gt

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Development of a quality assessment tool for systematic reviews of observational studies (QATSO) of HIV prevalence in men having sex with men and associated risk behaviours

<p>Abstract</p> <p>Background</p> <p>Systematic reviews based on the critical appraisal of observational and analytic studies on HIV prevalence and risk factors for HIV transmission among men having sex with men are very useful for health care decisions and planning. Such appraisal is particularly difficult, however, as the quality assessment tools available for use with observational and analytic studies are poorly established.</p> <p>Methods</p> <p>We reviewed the existing quality assessment tools for systematic reviews of observational studies and developed a concise quality assessment checklist to help standardise decisions regarding the quality of studies, with careful consideration of issues such as external and internal validity.</p> <p>Results</p> <p>A pilot version of the checklist was developed based on epidemiological principles, reviews of study designs, and existing checklists for the assessment of observational studies. The Quality Assessment Tool for Systematic Reviews of Observational Studies (QATSO) Score consists of five items: External validity (1 item), reporting (2 items), bias (1 item) and confounding factors (1 item). Expert opinions were sought and it was tested on manuscripts that fulfil the inclusion criteria of a systematic review. Like all assessment scales, QATSO may oversimplify and generalise information yet it is inclusive, simple and practical to use, and allows comparability between papers.</p> <p>Conclusion</p> <p>A specific tool that allows researchers to appraise and guide study quality of observational studies is developed and can be modified for similar studies in the future.</p