The Silent Epidemic: Perspectives of High School Dropouts

Presents findings from a survey that examines why some students do not complete their high school education, and what academic and personal supports would have helped them stay in school. Includes recommendations for improving graduation rates

Scenario-led modelling of broadleaf forest expansion in Wales

Context Significant changes in the composition and extent of the UK forest cover are likely to take place in the coming decades. Current policy targets an increase in forest area, for example the Welsh Government aims for forest expansion by 2030, and a purposeful shift from non-native conifers to broadleaved tree species, as identified by the UK Forestry Standard Guidelines on Biodiversity. Objectives Using the example of Wales, we aim to generate evidence-based projection of impact of contrasting policy scenarios on the state of forests in the near future, with the view of stimulating debate and aiding decisions concerning plausible outcomes of different policies. Methods We quantified changes in different land use and land cover (LULC) classes in Wales between 2007 and 2015 and used a Multi-layer perceptron-Markov chain ensemble modelling approach to project the state of Welsh forests in 2030 under the current and an alternate policy scenario. Results The current level of expansion and restoration of broadleaf forest in Wales is sufficient to deliver on existing policy goals. We also show effects of a more ambitious afforestation policy on the Welsh landscape. In a key finding, the highest intensity of broadleaf expansion is likely to shift from south-eastern to a more central areas of Wales. Conclusion The study identifies the key predictors of LULC change in Wales. High resolution future land cover simulation maps using these predictors offers an evidence-based tool for forest managers and government officials to test effects of existing and alternative policy scenarios

A cross-sector analysis of human and organisational factors in the deployment of data-driven predictive maintenance

Domains such as utilities, power generation, manufacturing and transport are increasingly turning to data-driven tools for management and maintenance of key assets. Whole ecosystems of sensors and analytical tools can provide complex, predictive views of network asset performance. Much research in this area has looked at the technology to provide both sensing and analysis tools. The reality in the field, however, is that the deployment of these technologies can be problematic due to user issues, such as interpretation of data or embedding within processes, and organisational issues, such as business change to gain value from asset analysis. 13 experts from the field of remote condition monitoring, asset management and predictive analytics across multiple sectors were interviewed to ascertain their experience of supplying data-driven applications. The results of these interviews are summarised as a framework based on a predictive maintenance project lifecycle covering project motivations and conception, design and development, and operation. These results identified critical themes for success around having a target or decision-led, rather than data-led, approach to design; long-term resourcing of the deployment; the complexity of supply chains to provide data-driven solutions and the need to maintain knowledge across the supply chain; the importance of fostering technical competency in end-user organisations; and the importance of a maintenance-driven strategy in the deployment of data-driven asset management. Emerging from these themes are recommendations related to culture, delivery process, resourcing, supply chain collaboration and industry-wide cooperation

Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR) trial [NCT00256139]

BACKGROUND: Chronic psoriasis can negatively affect patients' lives. Assessing the impact of treatment on different aspects of a patient's health-related quality of life (HRQOL) is therefore important and relevant in trials of anti-psoriasis agents. The recombinant humanized IgG(1 )monoclonal antibody efalizumab targets multiple T-cell-dependent steps in the immunopathogenesis of psoriasis. Efalizumab has demonstrated safety and efficacy in several clinical trials, and improves patients' quality of life. Objective: To evaluate the impact of efalizumab on HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis, including a large cohort of High-Need patients for whom at least 2 other systemic therapies were unsuitable because of lack of efficacy, intolerance, or contraindication. METHODS: A total of 793 patients were randomized in a 2:1 ratio to receive efalizumab 1 mg/kg/wk (n = 529) or placebo (n = 264) for 12 weeks. The study population included 526 High-Need patients (342 efalizumab, 184 placebo). The treatment was evaluated by patients using the HRQOL assessment tools Short Form-36 (SF-36) and Dermatology Life Quality Index (DLQI). Other patient-reported assessments included the Psoriasis Symptom Assessment (PSA), a visual analog scale (VAS) for itching, and the Patient's Global Psoriasis Assessment (PGPA). RESULTS: Efalizumab was associated with improvements at Week 12 from baseline in patient-reported outcomes, both in the total study population and in the High-Need cohort. Among all efalizumab-treated patients, the DLQI improved by 5.7 points from baseline to Week 12, relative to an improvement of 2.3 points for placebo patients (P < .001). Corresponding improvements in DLQI in the High-Need cohort were 5.4 points for efalizumab compared to 2.3 for placebo (P < .001). Improvements from baseline on the SF-36, PSA, PGPA, and itching VAS at Week 12 were also significantly greater in efalizumab-treated patients than for placebo. CONCLUSION: A 12-week course of efalizumab improved HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis. The benefits of efalizumab therapy in High-Need patients were similar to those observed in the total study population, indicating that the beneficial impact of efalizumab on QOL is consistent regardless of disease severity, prior therapy, or contraindications to previous therapies

Comparative analysis of sequence characteristics of imprinted genes in human, mouse, and cattle

Genomic imprinting is an epigenetic mechanism that results in monoallelic expression of genes depending on parent-of-origin of the allele. Although the conservation of genomic imprinting among mammalian species has been widely reported for many genes, there is accumulating evidence that some genes escape this conservation. Most known imprinted genes have been identified in the mouse and human, with few imprinted genes reported in cattle. Comparative analysis of genomic imprinting across mammalian species would provide a powerful tool for elucidating the mechanisms regulating the unique expression of imprinted genes. In this study we analyzed the imprinting of 22 genes in human, mouse, and cattle and found that in only 11 was imprinting conserved across the three species. In addition, we analyzed the occurrence of the sequence elements CpG islands, C + G content, tandem repeats, and retrotransposable elements in imprinted and in nonimprinted (control) cattle genes. We found that imprinted genes have a higher G + C content and more CpG islands and tandem repeats. Short interspersed nuclear elements (SINEs) were notably fewer in number in imprinted cattle genes compared to control genes, which is in agreement with previous reports for human and mouse imprinted regions. Long interspersed nuclear elements (LINEs) and long terminal repeats (LTRs) were found to be significantly underrepresented in imprinted genes compared to control genes, contrary to reports on human and mouse. Of considerable significance was the finding of highly conserved tandem repeats in nine of the genes imprinted in all three species

Assessing household wealth in health studies in developing countries: a comparison of participatory wealth ranking and survey techniques from rural South Africa

BACKGROUND: Accurate tools for assessing household wealth are essential for many health studies in developing countries. Household survey and participatory wealth ranking (PWR) are two approaches to generate data for this purpose. METHODS: A household survey and PWR were conducted among eight villages in rural South Africa. We developed three indicators of household wealth using the data. One indicator used PWR data only, one used principal components analysis to combine data from the survey, while the final indicator used survey data combined in a manner informed by the PWR. We assessed internal consistency of the indices and assessed their level of agreement in ranking household wealth. RESULTS: Food security, asset ownership, housing quality and employment were important indicators of household wealth. PWR, consisting of three independent rankings of 9671 households, showed a high level of internal consistency (intraclass correlation coefficient 0.81, 95% CI 0.79-0.82). Data on 1429 households were available from all three techniques. There was moderate agreement in ranking households into wealth tertiles between the two indicators based on survey data (spearman rho = 0.69, kappa = 0.43), but only limited agreement between these techniques and the PWR data (spearman rho = 0.38 and 0.31, kappa = 0.20 and 0.17). CONCLUSION: Both PWR and household survey can provide a rapid assessment of household wealth. Each technique had strengths and weaknesses. Reasons for differences might include data inaccuracies or limitations in the methods by which information was weighted. Alternatively, the techniques may measure different things. More research is needed to increase the validity of measures of socioeconomic position used in health studies in developing countries

Wolf Rock lighthouse: past developments and future survivability under wave loading

Lighthouses situated on exposed rocky outcrops warn mariners of the dangers that lurk beneath the waves. They were first constructed when approaches to wave loading and structural response were relatively unsophisticated, essentially learning from previous failures. Here, we chart the evolution of lighthouses on the Wolf Rock, situated between Land's End and the Isles of Scilly in the UK. The first empirical approaches are described, followed by design aspects of the present tower, informed by innovations developed on other rocky outcrops. We focus on a particular development associated with the automation of lighthouses: the helideck platform. The design concept is described and the structure then scrutinized for future survivability, using the latest structural modelling techniques of the entire lighthouse and helideck. Model validation data were obtained through a complex logistical field operation and experimental modal analysis. Extreme wave loading for the model required the identification of the 250-year return period wave using a Bayesian method with informative prior distributions, for two different scenarios (2017 and 2067). The structural models predict responses of the helideck to wave loading which is characterized by differential displacements of 0.093m (2017) and 0.115m (2067) with associated high tension forces and plastic strain.</p

Increased dynamics in the 40-57 Ω-loop of the G41S variant of human cytochrome c promote its pro-apoptotic conformation

Thrombocytopenia 4 is an inherited autosomal dominant thrombocytopenia, which occurs due to mutations in the human gene for cytochrome c that results in enhanced mitochondrial apoptotic activity. The Gly41Ser mutation was the first to be reported. Here we report stopped-flow kinetic studies of azide binding to human ferricytochrome c and its Gly41Ser variant, together with backbone amide H/D exchange and 15N-relaxation dynamics using NMR spectroscopy, to show that alternative conformations are kinetically and thermodynamically more readily accessible for the Gly41Ser variant than for the wild-type protein. Our work reveals a direct conformational link between the 40-57 Ω-loop in which residue 41 resides and the dynamical properties of the axial ligand to the heme iron, Met80, such that the replacement of glycine by serine promotes the dissociation of the Met80 ligand, thereby increasing the population of a peroxidase active state, which is a key non-native conformational state in apoptosis