Exponentially Increasing Incidences of Cutaneous Malignant Melanoma in Europe Correlate with Low Personal Annual UV Doses and Suggests 2 Major Risk Factors

For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection

Variation in the use of observation status evaluation in Massachusetts acute care hospitals, 2003–2006

Background Observation evaluation is an alternate pathway to inpatient admission following Emergency Department (ED) assessment. Aims We aimed to describe the variation in observation use and charges between acute care hospitals in Massachusetts from 2003 to 2006. Methods Retrospective pilot analysis of hospital administrative data. Patients discharged from a Massachusetts hospital between 2003 and 2006 after an observation visit or inpatient hospitalization for six emergency medical conditions, grouped by the Clinical Classification System (CCS), were included. Patients discharged with a primary obstetric condition were excluded. The primary outcome measure, “Observation Proportion ” (pOBS), was the use of observation evaluation relative to inpatient evaluation (pOBS = n Observation/(n Observation + n Inpatient). We calculated pOBS, descriptive statistics of use and charges by the hospital for each condition. Results From 2003 to 2006 the number of observation visits in Massachusetts increased 3.9 % [95 % confidence interval (CI) 3.8 % to 4.0%] from 128,825 to 133,859, while inpatient hospitalization increased 1.29 % (95 % CI 1.26 % to 1.31%) from 832,415 to 843,617. Nonspecific chest pain (CCS 102) was the most frequently observed condition with 85,843 (16.3 % of total) observation evaluations. Observation visits for nonspecific chest pain increased 43.5 % from 2003 to 2006. Relative observation utilization (pOBS) for nonspecific chest pain ranged from 25 % to 95% across hospitals. Wide variation in hospital use of observation and charges was seen for all six emergency medical conditions. Conclusions There was wide variation in use of observation across six common emergency conditions in Massachusetts in this pilot analysis. This variation may have a substantial impact on hospital resource utilization. Further investigation into the patient, provider and hospital-level characteristics that explain the variation in observation use could help improve hospital efficiency

An estimate of carbon emissions from 2004 wildfires across Alaskan Yukon River Basin

© 2007 Tan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

BMP-9 induced endothelial cell tubule formation and inhibition of migration involves Smad1 driven endothelin-1 production.

BACKGROUND: Bone morphogenetic proteins (BMPs) and their receptors, such as bone morphogenetic protein receptor (BMPR) II, have been implicated in a wide variety of disorders including pulmonary arterial hypertension (PAH). Similarly, endothelin-1 (ET-1), a mitogen and vasoconstrictor, is upregulated in PAH and endothelin receptor antagonists are used in its treatment. We sought to determine whether there is crosstalk between BMP signalling and the ET-1 axis in human pulmonary artery endothelial cells (HPAECs), possible mechanisms involved in such crosstalk and functional consequences thereof. METHODOLOGY/PRINCIPAL FINDING: Using western blot, real time RT-PCR, ELISA and small RNA interference methods we provide evidence that in HPAECs BMP-9, but not BMP-2, -4 and -6 significantly stimulated ET-1 release under physiological concentrations. This release is mediated by both Smad1 and p38 MAPK and is independent of the canonical Smad4 pathway. Moreover, knocking down the ALK1 receptor or BMPR II attenuates BMP-9 stimulated ET-1 release, whilst causing a significant increase in prepro ET-1 mRNA transcription and mature peptide release. Finally, BMP-9 induced ET-1 release is involved in both inhibition of endothelial cell migration and promotion of tubule formation. CONCLUSIONS/SIGNIFICANCE: Although our data does not support an important role for BMP-9 as a source of increased endothelial ET-1 production seen in human PAH, BMP-9 stimulated ET-1 production is likely to be important in angiogenesis and vascular stability. However, increased ET-1 production by endothelial cells as a consequence of BMPR II dysfunction may be clinically relevant in the pathogenesis of PAH

Identifying variants that contribute to linkage for dichotomous and quantitative traits in extended pedigrees

Compared to genome-wide association analysis, linkage analysis is less influenced by allelic heterogeneity. The use of linkage information in large families should provide a great opportunity to identify less frequent variants. We perform a linkage scan for both dichotomous and quantitative traits in eight extended families. For the dichotomous trait, we identified one linkage region on chromosome 4q. For quantitative traits, we identified two regions on chromosomes 4q and 6p for Q1 and one region on chromosome 6q for Q2. To identify variants that contribute to these linkage signals, we performed standard association analysis in genomic regions of interest. We also screened less frequent variants in the linkage region based on the risk ratio and phenotypic distribution among carriers. Two rare variants at VEGFC and one common variant on chromosome 4q conferred the greatest risk for the dichotomous trait. We identified two rare variants on chromosomes 4q (VEGFC) and 6p (VEGFA) that explain 12.4% of the total phenotypic variance of trait Q1. We also identified four variants (including one at VNN3) on chromosome 6q that are able to drop the linkage LOD from 3.7 to 1.0. These results suggest that the use of classical linkage and association methods in large families can provide a useful approach to identifying variants that are responsible for diseases and complex traits in families

Evaluation of a novel nutrition education intervention for medical students from across England

Objectives: Problems such as hospital malnutrition (∼40% prevalence in the UK) may be managed better by improving the nutrition education of 'tomorrow's doctors'. The Need for Nutrition Education Programme aimed to measure the effectiveness and acceptability of an educational intervention on nutrition for medical students in the clinical phase of their training. Design: An educational needs analysis was followed by a consultative process to gain consensus on a suitable educational intervention. This was followed by two identical 2-day educational interventions with before and after analyses of Knowledge, Attitudes and Practices (KAP). The 2-day training incorporated six key learning outcomes. Setting: Two constituent colleges of Cambridge University used to deliver the above educational interventions. Participants: An intervention group of 100 clinical medical students from 15 medical schools across England were recruited to attend one of two identical intensive weekend workshops. Primary and secondary outcome measures: The primary outcome measure consisted of change in KAP scores following intervention using a clinical nutrition questionnaire. Secondary outcome measures included change in KAP scores 3 months after the intervention as well as a student-led semiqualitative evaluation of the educational intervention. Results: Statistically significant changes in KAP scores were seen immediately after the intervention, and this was sustained for 3 months. Mean differences and 95% CIs after intervention were Knowledge 0.86 (0.43 to 1.28); Attitude 1.68 (1.47 to 1.89); Practice 1.76 (1.11 to 2.40); KAP 4.28 (3.49 to 5.06). Ninety-seven per cent of the participants rated the overall intervention and its delivery as 'very good to excellent', reporting that they would recommend this educational intervention to colleagues. Conclusion: Need for Nutrition Education Programme has highlighted the need for curricular innovation in the area of clinical health nutrition in medical schools. This project also demonstrates the effectiveness and acceptability of such a curriculum intervention for 'tomorrow's doctors'. Doctors, dietitians and nutritionists worked well in an effective interdisciplinary partnership when teaching medical students, providing a good model for further work in a healthcare setting

Childhood loneliness as a predictor of adolescent depressive symptoms: an 8-year longitudinal study

Childhood loneliness is characterised by children’s perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed

Impacts of organic and conventional crop management on diversity and activity of free-living nitrogen fixing bacteria and total bacteria are subsidiary to temporal effects

A three year field study (2007-2009) of the diversity and numbers of the total and metabolically active free-living diazotophic bacteria and total bacterial communities in organic and conventionally managed agricultural soil was conducted at the Nafferton Factorial Systems Comparison (NFSC) study, in northeast England. The result demonstrated that there was no consistent effect of either organic or conventional soil management across the three years on the diversity or quantity of either diazotrophic or total bacterial communities. However, ordination analyses carried out on data from each individual year showed that factors associated with the different fertility management measures including availability of nitrogen species, organic carbon and pH, did exert significant effects on the structure of both diazotrophic and total bacterial communities. It appeared that the dominant drivers of qualitative and quantitative changes in both communities were annual and seasonal effects. Moreover, regression analyses showed activity of both communities was significantly affected by soil temperature and climatic conditions. The diazotrophic community showed no significant change in diversity across the three years, however, the total bacterial community significantly increased in diversity year on year. Diversity was always greatest during March for both diazotrophic and total bacterial communities. Quantitative analyses using qPCR of each community indicated that metabolically active diazotrophs were highest in year 1 but the population significantly declined in year 2 before recovering somewhat in the final year. The total bacterial population in contrast increased significantly each year. Seasonal effects were less consistent in this quantitative study