Age and petrogenesis of the Lundy granite: Paleocene intraplate peraluminous magmatism in the Bristol Channel, UK

This is the author accepted manuscript. The final version is available from Geological Society via the DOI in this record.The Lundy granite forms part of the Lundy Igneous Complex, which is the southernmost substantive expression of magmatism within both the British Cenozoic Igneous Province and the wider North Atlantic Igneous Province. Its Qz + Pl + Kfs + Bt ± Grt ± Tpz mineralogy and peraluminous character contrast with other British Cenozoic Igneous Province granites farther north but are similar to the granites of the adjacent Early Permian Cornubian Batholith. We present the results of mapping, petrographical and mineral chemical analysis, and the first U–Pb zircon ages for the granite (59.8 ± 0.4 – 58.4 ± 0.4 Ma) and cross-cutting basic dykes (57.2 ± 0.5 Ma), which confirm a Paleocene age for magmatism. Zircon inheritance is limited but two cores imply the presence of Early Palaeozoic igneous rocks in the unexposed basement of SW England. The anomalous southerly location of the Lundy Igneous Complex is a consequence of mantle melting arising from the superimposition of localized lithospheric extension, related to intraplate strike-slip tectonics, with the distal ancestral Icelandic plume. Granite generation primarily reflects crustal partial melting during the emplacement of mantle-derived melts. The change in geochemical character between the Lundy granite (peraluminous) and other British Cenozoic Igneous Province granites (metaluminous or subalkaline) indicates a fundamental crustal source control between contrasting peri-Gondwanan and Laurentian basement provinces.Financial assistance was received from University College Oxford, the Geologists’ Association, the Lundy Field Society and the Burdett-Coutts fund

Double quantum dot with integrated charge sensor based on Ge/Si heterostructure nanowires

Coupled electron spins in semiconductor double quantum dots hold promise as the basis for solid-state qubits. To date, most experiments have used III-V materials, in which coherence is limited by hyperfine interactions. Ge/Si heterostructure nanowires seem ideally suited to overcome this limitation: the predominance of spin-zero nuclei suppresses the hyperfine interaction and chemical synthesis creates a clean and defect-free system with highly controllable properties. Here we present a top gate-defined double quantum dot based on Ge/Si heterostructure nanowires with fully tunable coupling between the dots and to the leads. We also demonstrate a novel approach to charge sensing in a one-dimensional nanostructure by capacitively coupling the double dot to a single dot on an adjacent nanowire. The double quantum dot and integrated charge sensor serve as an essential building block required to form a solid-state spin qubit free of nuclear spin.Comment: Related work at http://marcuslab.harvard.edu and http://cmliris.harvard.ed

Antiretroviral Therapy outcomes among adolescents and youth in rural Zimbabwe

Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents) 15.1-19 years (adolescents), 19.1-24 years (young adults) and 24.1-29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35). Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults

What is the comparative health status and associated risk factors for the Métis? A population-based study in Manitoba, Canada

<p>Abstract</p> <p>Background</p> <p>Métis are descendants of early 17^thcentury relationships between North American Indians and Europeans. This study's objectives were: (1) to compare the health status of the Métis people to all other residents of Manitoba, Canada; and (2) to analyze factors in predicting the likelihood of diabetes and related lower limb amputation.</p> <p>Methods</p> <p>Using de-identified administrative databases plus the Métis Population Database housed at the Manitoba Centre for Health Policy, age/sex-adjusted rates of mortality and disease were calculated for Métis (n = 73,016) and all other Manitobans (n = 1,104,672). Diseases included: hypertension, arthritis, diabetes, ischemic heart disease (age 19+); osteoporosis (age 50+); acute myocardial infarction (AMI) and stroke (age 40+); total respiratory morbidity (TRM, all ages). Using logistic regression, predictors of diabetes (2004/05-2006/07) and diabetes-related lower-limb amputations (2002/03-2006/07) were analyzed.</p> <p>Results</p> <p>Disease rates were higher for Métis compared to all others: premature mortality before age 75 (4.0 vs. 3.3 per 1000, p < .001); total mortality (9.7 vs. 8.4 per 1000, p < .001); injury mortality (0.58 vs. 0.51 per 1000, p < .03); Potential Years of Life Lost (64.6 vs. 54.6 per 1000, p < .001); all-cause 5-year mortality for people with diabetes (20.8% vs. 18.6%, p < .02); hypertension (27.9% vs. 24.8%, p < .001); arthritis (24.2% vs. 19.9%, p < .001), TRM (13.6% vs. 10.6%, p < .001); diabetes (11.8% vs. 8.8%, p < .001); diabetes-related lower limb amputation (24.1 vs. 16.2 per 1000, p < .001); ischemic heart disease (12.2% vs. 8.7%, p < .001); osteoporosis (12.2% vs. 12.3%, NS), dialysis initiation (0.46% vs. 0.34%, p < .001); AMI (5.4 vs. 4.3 per 1000, p < .001); stroke (3.6 vs. 2.9 per 1000, p < .001). Controlling for geography, age, sex, income, continuity of care and comorbidities, Métis were more likely to have diabetes (aOR = 1.29, 95% CI 1.25-1.34), but not diabetes-related lower limb amputation (aOR = 1.13, 95% CI 0.90-1.40, NS). Continuity of care was associated with decreased risk of amputation both provincially (aOR = 0.71, 95% CI 0.62-0.81) and for Métis alone (aOR = 0.62, 95% CI 0.40-0.96).</p> <p>Conclusion</p> <p>Despite universal healthcare, Métis' illness and mortality rates are mostly higher. Although elevated diabetes risk persists for the Métis even after adjusting for sociodemographic, healthcare and comorbidity variables, the risk of amputation for Métis appears more related to healthcare access rather than ethnicity.</p

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Cost-Effective Use of Silver Dressings for the Treatment of Hard-to-Heal Chronic Venous Leg Ulcers

Aim To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs). Background Chronic venous ulceration affects 1–3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial. Methods A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: ‘Healed ulcer’, ‘Healing ulcer’ or ‘No improvement’ were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model. Results Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings. Conclusion The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs

Interactions between downslope flows and a developing cold-air pool

A numerical model has been used to characterize the development of a region of enhanced cooling in an alpine valley with a width of order (Formula presented.) km, under decoupled stable conditions. The region of enhanced cooling develops largely as a region of relatively dry air which partitions the valley atmosphere dynamics into two volumes, with airflow partially trapped within the valley by a developing elevated inversion. Complex interactions between the region of enhanced cooling and the downslope flows are quantified. The cooling within the region of enhanced cooling and the elevated inversion is almost equally partitioned between radiative and dynamic effects. By the end of the simulation, the different valley atmospheric regions approach a state of thermal equilibrium with one another, though this cannot be said of the valley atmosphere and its external environment.Peer reviewe

Post-puff respiration measures on smokers of different tar yield cigarettes

The purpose of this study was to determine the effect of different tar yield cigarette brands on the post-puff inhalation/exhalation depth and duration for established smokers of the brands. The study was conducted with 74 established smokers of 1–17 mg Federal Trade Commission (FTC) tar products. The subjects were participating in a five-day inpatient clinical biomarker study during which time they were allowed to smoke their own brand of cigarette whenever they wished. On two separate days, the subjects' breathing pattern was measured using respiratory inductive plethysmography while they smoked one cigarette. This enabled the measurement of the post-puff inhalation volume, exhalation volume, inhalation duration, and exhalation duration for each subject after each puff on two of their own brand of cigarettes