Single-dose administration of Bowman-Birk inhibitor concentrate in patients with oral leukoplakia.

The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor and a potential cancer chemopreventive agent for humans. In this Phase I clinical trial, BBI concentrate was administered as a single oral dose to 24 subjects with oral leukoplakia. Pharmacokinetics of BBI was analyzed, and subjects were monitored clinically for toxic effects. Subjects received between 25 and 800 chymotrypsin inhibitor units (CIU) of the compound in a dose escalation trial. BBI was taken up rapidly, and a metabolic product of BBI was excreted in the urine within 24-48 h. No clinical or laboratory evidence of toxicity was observed in the study. Protease activity was also measured in buccal cells to evaluate usefulness as a biomarker. Single-dose BBI concentrate administered up to 800 CIU was well tolerated and appeared to be nontoxic. Further investigation in Phase II clinical trials is being done

Strengths and weaknesses in the implementation of maternal and perinatal death reviews in Tanzania: perceptions, processes and practice.

OBJECTIVES: Tanzania institutionalised maternal and perinatal death reviews (MPDR) in 2006, yet there is scarce evidence on the extent and quality of implementation of the system. We reviewed the national policy documentation and explored stakeholders' involvement in, and perspectives of, the role and practices of MPDR in district and regional hospitals, and assessed current capacity for achieving MPDR. METHODS: We reviewed the national MPDR guidelines and conducted a qualitative study using semi-structured interviews. Thirty-two informants in Mara Region were interviewed within health administration and hospitals, and five informants were included at the central level. Interviews were analysed for comparison of statements across health system level, hospital, profession and MPDR experience. RESULTS: The current MPDR system does not function adequately to either perform good quality reviews or fulfil the aspiration to capture every facility-based maternal and perinatal death. Informants at all levels express differing understandings of the purpose of MPDR. Hospital reviews fail to identify appropriate challenges and solutions at the facility level. Staff are committed to the process of maternal death review, with routine documentation and reporting, yet action and response are insufficient. CONCLUSION: The confusion between MPDR and maternal death surveillance and response results in a system geared towards data collection and surveillance, failing to explore challenges and solutions from within the remit of the hospital team. This reduces the accountability of the health workers and undermines opportunities to improve quality of care. We recommend initiatives to strengthen the quality of facility-level reviews in order to establish a culture of continuous quality of care improvement and a mechanism of accountability within facilities. Effective facility reviews are an important peer-learning process that should remain central to quality of care improvement strategies.<br/

Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes

Arduous implementation: Does the Normalisation Process Model explain why it's so difficult to embed decision support technologies for patients in routine clinical practice

Background: decision support technologies (DSTs, also known as decision aids) help patients and professionals take part in collaborative decision-making processes. Trials have shown favorable impacts on patient knowledge, satisfaction, decisional conflict and confidence. However, they have not become routinely embedded in health care settings. Few studies have approached this issue using a theoretical framework. We explained problems of implementing DSTs using the Normalization Process Model, a conceptual model that focuses attention on how complex interventions become routinely embedded in practice.Methods: the Normalization Process Model was used as the basis of conceptual analysis of the outcomes of previous primary research and reviews. Using a virtual working environment we applied the model and its main concepts to examine: the 'workability' of DSTs in professional-patient interactions; how DSTs affect knowledge relations between their users; how DSTs impact on users' skills and performance; and the impact of DSTs on the allocation of organizational resources.Results: conceptual analysis using the Normalization Process Model provided insight on implementation problems for DSTs in routine settings. Current research focuses mainly on the interactional workability of these technologies, but factors related to divisions of labor and health care, and the organizational contexts in which DSTs are used, are poorly described and understood.Conclusion: the model successfully provided a framework for helping to identify factors that promote and inhibit the implementation of DSTs in healthcare and gave us insights into factors influencing the introduction of new technologies into contexts where negotiations are characterized by asymmetries of power and knowledge. Future research and development on the deployment of DSTs needs to take a more holistic approach and give emphasis to the structural conditions and social norms in which these technologies are enacte

Simulations of events for the LUX-ZEPLIN (LZ) dark matter experiment

The LUX-ZEPLIN dark matter search aims to achieve a sensitivity to the WIMP-nucleon spin-independent cross-section down to (1–2)×10−12 pb at a WIMP mass of 40 GeV/c2. This paper describes the simulations framework that, along with radioactivity measurements, was used to support this projection, and also to provide mock data for validating reconstruction and analysis software. Of particular note are the event generators, which allow us to model the background radiation, and the detector response physics used in the production of raw signals, which can be converted into digitized waveforms similar to data from the operational detector. Inclusion of the detector response allows us to process simulated data using the same analysis routines as developed to process the experimental data

Modelling the nucleon wave function from soft and hard processes

Current light-cone wave functions for the nucleon are unsatisfactory since they are in conflict with the data of the nucleon's Dirac form factor at large momentum transfer. Therefore, we attempt a determination of a new wave function respecting theoretical ideas on its parameterization and satisfying the following constraints: It should provide a soft Feynman contribution to the proton's form factor in agreement with data; it should be consistent with current parameterizations of the valence quark distribution functions and lastly it should provide an acceptable value for the \jp \to N \bar N decay width. The latter process is calculated within the modified perturbative approach to hard exclusive reactions. A simultaneous fit to the three sets of data leads to a wave function whose $x$-dependent part, the distribution amplitude, shows the same type of asymmetry as those distribution amplitudes constrained by QCD sum rules. The asymmetry is however much more moderate as in those amplitudes. Our distribution amplitude resembles the asymptotic one in shape but the position of the maximum is somewhat shifted.Comment: 32 pages RevTex + PS-file with 5 figures in uu-encoded, compressed fil

First Measurement of Transferred Polarization in the Exclusive e p --> e' K+ Lambda Reaction

The first measurements of the transferred polarization for the exclusive ep --> e'K+ Lambda reaction have been performed in Hall B at the Thomas Jefferson National Accelerator Facility using the CLAS spectrometer. A 2.567 GeV electron beam was used to measure the hyperon polarization over a range of Q2 from 0.3 to 1.5 (GeV/c)2, W from 1.6 to 2.15 GeV, and over the full center-of-mass angular range of the K+ meson. Comparison with predictions of hadrodynamic models indicates strong sensitivity to the underlying resonance contributions. A non-relativistic quark model interpretation of our data suggests that the s-sbar quark pair is produced with spins predominantly anti-aligned. Implications for the validity of the widely used 3P0 quark-pair creation operator are discussed.Comment: 6 pages, 4 figure

Periodic eclipses of the young star PDS 110 discovered with WASP and KELT photometry

We report the discovery of eclipses by circumstellar disc material associated with the young star PDS 110 in the Ori OB1a association using the SuperWASP and Kilodegree Extremely Little Telescope surveys. PDS 110 (HD 290380, IRAS 05209-0107) is a rare Fe/Ge-type star, an similar to 10 Myr-old accreting intermediate-mass star showing strong infrared excess (L-IR/L-bol similar or equal to 0.25). Two extremely similar eclipses with a depth of 30 per cent and duration similar to 25 d were observed in 2008 November and 2011 January. We interpret the eclipses as caused by the same structure with an orbital period of 808 +/- 2 d. Shearing over a single orbit rules out diffuse dust clumps as the cause, favouring the hypothesis of a companion at similar to 2 au. The characteristics of the eclipses are consistent with transits by an unseen low-mass (1.8-70M(Jup)) planet or brown dwarf with a circumsecondary disc of diameter similar to 0.3 au. The next eclipse event is predicted to take place in 2017 September and could be monitored by amateur and professional observatories across the world

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

The importance of post-translocation monitoring of habitat use and population growth: insights from a Seychelles Warbler (Acrocephalus sechellensis) translocation

Translocations are a valuable tool within conservation, and when performed successfully can rescue species from extinction. However, to label a translocation a success, extensive post-translocation monitoring is required, ensuring the population is growing at the expected rate. In 2011, a habitat assessment identified Frégate Island as a suitable island to host a Seychelles Warbler (Acrocephalus sechellensis) population. Later that year, 59 birds were translocated from Cousin Island to Frégate Island. Here, we determine Seychelles Warbler habitat use and population growth on Frégate Island, assessing the status of the translocation and identifying any interventions that may be required. We found that territory quality, an important predictor of fledgling production on Cousin Island, was a poor predictor of bird presence on Frégate Island. Instead, tree diversity, middle-storey vegetation density, and broad-leafed vegetation density all predicted bird presence positively. A habitat suitability map based on these results suggests most of Frégate Island contains either a suitable or a moderately suitable habitat, with patches of unsuitable overgrown coconut plantation. To achieve the maximum potential Seychelles Warbler population size on Frégate Island, we recommend habitat regeneration, such that the highly diverse subset of broad-leafed trees and a dense middle storey should be protected and replace the unsuitable coconut. Frégate Island’s Seychelles Warbler population has grown to 141 birds since the release, the slowest growth rate of all Seychelles Warbler translocations; the cause of this is unclear. This study highlights the value of post-translocation monitoring, identifying habitat use and areas requiring restoration, and ultimately ensuring that the population is growing