HSV-1 gM and the gK/pUL20 complex are important for the localization of gD and gH/L to viral assembly sites.

Herpes simplex virus-1 (HSV-1), like all herpesviruses, is a large complex DNA virus containing up to 16 different viral membrane proteins in its envelope. The assembly of HSV-1 particles occurs by budding/wrapping at intracellular membranes producing infectious virions contained within the lumen of cytoplasmic membrane-bound compartments that are then released by secretion. To ensure incorporation of all viral membrane proteins into the envelope, they need to be localized to the appropriate intracellular membranes either via the endocytic pathway or by direct targeting to assembly sites from the biosynthetic secretory pathway. Many HSV-1 envelope proteins encode targeting motifs that direct their endocytosis and targeting, while others do not, including the essential entry proteins gD and the gH/gL complex, and so it has been unclear how these envelope proteins reach the appropriate assembly compartments. We now show that efficient endocytosis of gD and gH/gL and their incorporation into mature virions relies upon the presence of the HSV-1 envelope proteins gM and the gK/pUL20 complex. Our data demonstrate both redundant and synergistic roles for gM and gK/pUL20 in controlling the targeting of gD and gH/L to the appropriate intracellular virus assembly compartments.This work was supported by the Biotechnology and Biological Sciences Research Council UK (Ph.D. studentship to S.-Y.K.L.), and the Royal Society (UF090010).This is the final published version. It first appeared at http://www.mdpi.com/1999-4915/7/3/915

Pseudotumor cerebri syndrome in childhood : incidence, clinical profile and risk factors in a national prospective population-based cohort study

Aim To investigate the epidemiology, clinical profile and risk factors of pseudotumor cerebri syndrome (PTCS) in children aged 1-16 years. Methods A national prospective population-based cohort study over 25 months. Newly diagnosed PTCS cases notified via British Paediatric Surveillance Unit (BPSU) were ascertained using classical diagnostic criteria and categorised according to 2013 revised diagnostic criteria. We derived national age, sex and weight-specific annual incidence rates and assessed effects of sex and weight category. Results We identified 185 PTCS cases of which 166 also fulfilled revised diagnostic criteria. The national annual incidence (95% CI) of childhood PTCS aged 1-16 years was 0.71 (0.57- 0.87) per 100,000 population increasing with age and weight to 4.18 and 10.7 per 100,000 in obese 12-15 year old boys and girls respectively. Incidence rates under 7 years were similar in both sexes. From 7 years onwards, the incidence in girls was double that in boys, but only in overweight (including obese) children. In 12-15 year old children, an estimated 82% of the incidence of PTCS was attributable to obesity. Two subgroups of PTCS were apparent: 168 (91%) cases aged from 7 years frequently presented on medication and with headache, and were predominantly female and obese. The remaining 17 (9%) cases under 7 years often lacked these risk factors and commonly presented with new onset squint. Conclusions This uniquely largest population-based study of childhood PTCS will inform the design of future intervention studies. It suggests that weight reduction is central to the prevention of PTCS

Development of Low Temperature, Aqueous Synthesis Method of Lead Sulfide Quantum Dots

Quantum dots have become an active area of research in the past decade due to their unique properties. Quantum confinement effects allow for efficient spectral conversion and size tunable fluorescence and absorption peaks. Near infrared spectral converting lead sulfide quantum dots have potential applications in solar power, biological imaging and communications technology. However at Cal Poly, lead sulfide dots have not been synthesized. The quantum dot synthesis currently adapted at Cal Poly encompasses organometallic precursors at high reaction temperatures, producing cadmium selenium dots. The organometallic approach has been found to produce nanocrystals with high quality photoluminescence, but due to its hazardous reaction parameters an environmentally safe synthesis is desired. The aim of this study was to adapt and develop an aqueous “green” synthesis method for producing lead sulfide quantum dots to Cal Poly. The method used within this study, previously reported Jiao, encompasses a low temperature aqueous synthesis method using low toxicity surfactant precursors SDS, CTAB and EDTA dissolved into deionized water heated to 70 C. A solution of lead acetate was injected into the surfactant solution to produce lead ion EDTA complexes. Thiourea solution was then slowly injected to introduce sulfur allowing lead sulfide to form. The formation of lead sulfide could be seen by the transformation of the solution from buff to dark brown. Samples taken from this solution were naturally cooled, centrifuged and rinsed with alcohol and DI water. Fluorescence and absorbance testing was conducted on produced samples to test for the presence of quantum dots. In addition, commercially purchased lead sulfide quantum dots were fluorescence tested for comparison to our samples

Early exclusion of major adverse cardiac events in emergency department chest pain patients: A prospective observational study

Background The current evaluation of patients with chest pain presenting to an emergency department (ED) with suspected acute coronary syndrome (ACS) is a lengthy process involving serial measurements of troponin. Objective We aimed to validate the diagnostic accuracy of a Thrombolysis in Myocardial Infarction (TIMI) score with single high-sensitive cardiac troponin T (hs-cTnT) for early rule out of 30-day major adverse cardiac events (MACE), and to compare the TIMI score with combinations of heart-type fatty acid binding protein (H-FABP) and a modified HEART (history, electrocardiogram, age, risk factors, troponin) score. Methods We recruited 602 consecutive adult patients with chest pain and suspected ACS in the ED. Each patient had TIMI and HEART scores, and a point-of-care H-FABP test. Results MACE occurred in 42 (7.0%) patients within 30 days. A low risk for 30-day MACE was identified by a modified TIMI score of 0 in 65 (11%) patients, and by a HEART score ≤ 2 in 96 (16%) patients. No MACE occurred in these groups, giving both scores a sensitivity of 100% (95% confidence interval [CI] 91.6–100%), and specificity of 11.6% (95% CI 9.2–14.5%) and 17.1% (95% CI 14.2–20.5%), respectively. Use of combined TIMI and HEART scores improved the specificity further to 22.0% (95% CI 18.7–25.6%) without lowering sensitivity. Early H-FABP measurement > 7 μg/L had a sensitivity of 41.5% (95% CI 27.8–56.6%) and a specificity of 91.1% (95% CI 88.4–93.2%) for predicting 30-day MACE. Conclusions A modified TIMI score of 0 or a HEART score of ≤ 2, incorporating a single hs-cTnT level, will identify patients with low risk of 30-day MACE for early discharge within 2 h of ED arrival

Epidemiology, prehospital care and outcomes of patients arriving by ambulance with dyspnoea: An observational study

Background: This study aimed to determine epidemiology and outcome for patients presenting to emergency departments (ED) with shortness of breath who were transported by ambulance. Methods: This was a planned sub-study of a prospective, interrupted time series cohort study conducted at three time points in 2014 and which included consecutive adult patients presenting to the ED with dyspnoea as a main symptom. For this sub-study, additional inclusion criteria were presentation to an ED in Australia or New Zealand and transport by ambulance. The primary outcomes of interest are the epidemiology and outcome of these patients. Analysis was by descriptive statistics and comparisons of proportions. Results: One thousand seven patients met inclusion criteria. Median age was 74 years (IQR 61-68) and 46.1 % were male. There was a high rate of co-morbidity and chronic medication use. The most common ED diagnoses were lower respiratory tract infection (including pneumonia, 22.7 %), cardiac failure (20.5%) and exacerbation of chronic obstructive pulmonary disease (19.7 %). ED disposition was hospital admission (including ICU) for 76.4 %, ICU admission for 5.6 % and death in ED in 0.9 %. Overall in-hospital mortality among admitted patients was 6.5 %. Discussion: Patients transported by ambulance with shortness of breath make up a significant proportion of ambulance caseload and have high comorbidity and high hospital admission rate. In this study, >60 % were accounted for by patients with heart failure, lower respiratory tract infection or COPD, but there were a wide range of diagnoses. This has implications for service planning, models of care and paramedic training. Conclusion: This study shows that patients transported to hospital by ambulance with shortness of breath are a complex and seriously ill group with a broad range of diagnoses. Understanding the characteristics of these patients, the range of diagnoses and their outcome can help inform training and planning of services

Predicting tree distributions in an East African biodiversity hotspot : model selection, data bias and envelope uncertainty

The Eastern Arc Mountains (EAMs) of Tanzania and Kenya support some of the most ancient tropical rainforest on Earth. The forests are a global priority for biodiversity conservation and provide vital resources to the Tanzanian population. Here, we make a first attempt to predict the spatial distribution of 40 EAM tree species, using generalised additive models, plot data and environmental predictor maps at sub 1 km resolution. The results of three modelling experiments are presented, investigating predictions obtained by (1) two different procedures for the stepwise selection of predictors, (2) down-weighting absence data, and (3) incorporating an autocovariate term to describe fine-scale spatial aggregation. In response to recent concerns regarding the extrapolation of model predictions beyond the restricted environmental range of training data, we also demonstrate a novel graphical tool for quantifying envelope uncertainty in restricted range niche-based models (envelope uncertainty maps). We find that even for species with very few documented occurrences useful estimates of distribution can be achieved. Initiating selection with a null model is found to be useful for explanatory purposes, while beginning with a full predictor set can over-fit the data. We show that a simple multimodel average of these two best-model predictions yields a superior compromise between generality and precision (parsimony). Down-weighting absences shifts the balance of errors in favour of higher sensitivity, reducing the number of serious mistakes (i.e., falsely predicted absences); however, response functions are more complex, exacerbating uncertainty in larger models. Spatial autocovariates help describe fine-scale patterns of occurrence and significantly improve explained deviance, though if important environmental constraints are omitted then model stability and explanatory power can be compromised. We conclude that the best modelling practice is contingent both on the intentions of the analyst (explanation or prediction) and on the quality of distribution data; generalised additive models have potential to provide valuable information for conservation in the EAMs, but methods must be carefully considered, particularly if occurrence data are scarce. Full results and details of all species models are supplied in an online Appendix. (C) 2008 Elsevier B.V. All rights reserved

Shear wave elastography of breast cancer:sensitivity according to histological type in a large cohort

PURPOSE: To define the shear wave elastography (SWE) characteristics of breast cancer histological types by size in a large cohort.METHODS: Consecutive patients with US visible masses underwent SWE. All those with confirmed invasive breast cancer were included in the study. Histologic type was ascertained from core biopsy and surgical resection specimens. For each type, mean and median values for Emean and Emax were ascertained. Commoner tumour types were further analysed by invasive size. The significance of differences was established using the Chi-square test.RESULTS: 1137 tumours constituted the study group. The proportion of tumours with Emean below 50 kPa was higher in tubular cancers (23%) compared to ductal carcinomas of no specific type (DNST) (6%) (p &lt; 0.001). Emax below 80 kPa was seen in 34% of tubular cancers compared to 16% of DNST (p &lt; 0.002). Emean and Emax for lobular, mucinous, papillary and metaplastic cancers were not different from those of DNST. There were no significant differences in Emean or Emax between tumour types once broken down according to invasive size.CONCLUSIONS: Most breast cancer histological types have similar SWE characteristics. The exception is tubular cancer which has significantly lower stiffness than other histologic types, accounted for largely by their small size.</p

Development, manufacturing, characterization, and modeling of a novel alumina/polysiloxane/boron carbide ablative composite

A novel class of alumina-reinforced, pre-ceramic resin matrix ablative composites was developed, manufactured, characterized, and modeled for use as a thermal protection system (TPS) material for extreme aerothermal environments. High alumina paper and twill-woven mullite fiber were investigated as reinforcements for a Techneglas Ultra High Temperature Resin (UHTR) pre-ceramic polysiloxane matrix composite. These 2D laminate alumina/UHTR (A/U) composites minimize peak back face temperature primarily through rapid melt advection and low through-thickness thermal conductivity. A loading study was performed for boron carbide (B₄C) as an additive and identified an optimal 7.5 wt% loading in UHTR, and the resulting changes to decomposition chemistry mechanisms were identified using analytical chemistry techniques. The bulk formation of networked Silicon Boron Oxycarbide (SiBOC) and precipitation of Highly Oriented Pyrolytic Graphite (HOPG) was identified in pyrolyzed and annealed UHTR with boron carbide. Four variants of A/U with and without boron carbide underwent aerothermal testing using an oxyacetylene test bed (OTB), whose flow field was characterized using Schlieren imaging and a low-cost enthalpy probe. Alumina Paper/UHTR with 7.5 wt% B4C (AP/UBC) was down selected to be the primary focus of thermal characterization and ablation material response (MR) modeling efforts in CMA, FIAT, and ITRAC, three industry standard one-dimensional ablation modeling codes. Ablative software outputs were compared against OTB experimental results to validate the AP/UBC material response model for use in preliminary design estimates for AP/UBC thicknesses of 0.100 inches or less.Materials Science and Engineerin

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy