CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts

Objective: To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. Methods: CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. Results: Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/μL in baseline CD4 strata 351-500, 501-650, and >650 cells/μL, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. Conclusions: Patients starting cART at high CD4 cell counts (>650 cells/μL) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death. Copyright © 2011 Lippincott Williams & Wilkins

Liquid Hydrogen Target Experience at SLAC

Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small "beer can" targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin-wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability.This paper surveys the evolution of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible

Interplay of Quantum Criticality and Geometric Frustration in Columbite

Motivated by CoNb2O6 (belonging to the columbite family of minerals), we theoretically study the physics of quantum ferromagnetic Ising chains coupled anti-ferromagnetically on a triangular lattice in the plane perpendicular to the chain direction. We combine exact solutions of the chain physics with perturbative approximations for the transverse couplings. When the triangular lattice has an isosceles distortion (which occurs in the real material), the T=0 phase diagram is rich with five different states of matter: ferrimagnetic, N\'eel, anti-ferromagnetic, paramagnetic and incommensurate phases, separated by quantum phase transitions. Implications of our results to experiments on CoNb2O6 are discussed

A Flagellar A-Kinase Anchoring Protein with Two Amphipathic Helices Forms a Structural Scaffold in the Radial Spoke Complex

A-kinase anchoring proteins (AKAPs) contain an amphipathic helix (AH) that binds the dimerization and docking (D/D) domain, RIIa, in cAMP-dependent protein kinase A (PKA). Many AKAPs were discovered solely based on the AH–RIIa interaction in vitro. An RIIa or a similar Dpy-30 domain is also present in numerous diverged molecules that are implicated in critical processes as diverse as flagellar beating, membrane trafficking, histone methylation, and stem cell differentiation, yet these molecules remain poorly characterized. Here we demonstrate that an AKAP, RSP3, forms a dimeric structural scaffold in the flagellar radial spoke complex, anchoring through two distinct AHs, the RIIa and Dpy-30 domains, in four non-PKA spoke proteins involved in the assembly and modulation of the complex. Interestingly, one AH can bind both RIIa and Dpy-30 domains in vitro. Thus, AHs and D/D domains constitute a versatile yet potentially promiscuous system for localizing various effector mechanisms. These results greatly expand the current concept about anchoring mechanisms and AKAPs

Ptarmigan Fiord basement-cover thrust imbricates, Baffin Island, Nunavut

The rocks at Ptarmigan Fiord on the Hall Peninsula of Baffin Island underwent midcrustal deformation during the formation of the Paleoproterozoic Trans-Hudson Orogen. The structural style in the region is dominated by imbricate panels of Archean basement orthogneiss and Paleoproterozoic supracrustal strata, interpreted to have been deformed by thick- skinned ductile thrusting. Basement rocks comprise amphibolite-facies metatonalite, metagranodiorite, metaquartz-diorite and metamonzogranite, and cover rocks comprise amphibolite-facies migmatitic pelitic and semipelitic schist, psammitic schist, amphibolite, calcsilicate and quartzite. The S 1a penetrative foliation is variably present in basement rocks and consis- tently present in cover rocks, and is defined by alignment of biotite, sillimanite and leucogranite that formed before and dur- ing the thermal metamorphic peak. The S 1a foliation was deformed by F 1b isoclinal folds with an amplitude of 100 m. These structures are interpreted as forming during a D 1 east-west crustal shortening event. Basement and cover imbrication oc- curred after the thermal metamorphic peak and is interpreted as D 2 thick-skinned ductile thrusting. Ductile thrust faults at the base of seven basement-cover slices are identified on the basis of repetition of units and strain localization, and are inter- preted as predominantly south-to-southeast verging on the basis of shear-sense indicators. There are two structural panels of D 2 thrust imbricates, one in the northwestern part of the map area and one in the eastern part of the map area. Map-scale crosscutting relationships indicate that the northwestern panel overthrusted the eastern panel on a southeasterly T 2c -di- rected thrust fault, following a F 2b folding event that folded the T 2a basement-cover thrust imbricates in the eastern panel. The Ptarmigan Fiord area contains a world-class exposure of thick-skinned structures as they are spectacularly delineated by belts of distinctive grey-weathering Archean basement rocks and brown- to black-weathering Paleoproterozoic supra- crustal rocks

Rabbit and Human Non-Keratinising Stratified Squamous Oesophageal Epithelium Displays Similar Microridge Structure by Scanning Electron Microscopy

Since the oesophageal epithelium of common laboratory animals, rats and mice, is keratinized it is unsuitable for comparison with typical non-keratinized stratified squamous human epithelium. It is thus important to find a suitable animal model for the study of human oesophageal tissue changes. This study investigated the microridge structure of immature and adult rabbit specimens, and adult human biopsies by scanning electron microscopy and morphometry. The investigation revealed a similarity between typical squamous human and adult rabbit oesophageal mucosal epithelium. While human epithelium specimens subdivided into two other groups (non-typical squamous and non-squamous); all typical squamous human biopsies were from patients who had normal endoscopy reports and no reflux symptoms. The surface cells of typical squamous human epithelium displayed complex microridge patterns (64% of cell surface) but patterns in non-typical squamous specimens were more variable (38%) (P \u3c 0.001) and cell boundaries less obvious. Rabbit squames displayed clear microridge patterns with an elevation in the percentage of cell surface covered by microridges, with increasing age, from immature to adult specimens (P \u3c 0.001). There was no statistically significant differences between adult rabbit, and \u27typical squamous\u27 human biopsies (range 51-65%), results which suggest potential use of a rabbit model to study changes in human oesophageal tissue

The Men's Safer Sex (MenSS) trial: protocol for a pilot randomised controlled trial of an interactive digital intervention to increase condom use in men

Sexually transmitted infections (STI) are a major public health problem. Condoms provide effective protection but there are many barriers to use. Face-to-face health promotion interventions are resource-intensive and show mixed results. Interactive digital interventions may provide a suitable alternative, allowing private access to personally tailored behaviour change support. We have developed an interactive digital intervention (the Men's Safer Sex (MenSS) website) which aims to increase condom use in men. We describe the protocol for a pilot trial to assess the feasibility of a full-scale randomised controlled trial of the MenSS website in addition to usual sexual health clinical care

Core competencies for pain management: results of an interprofessional consensus summit.

ObjectiveThe objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported.MethodsAn interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached.ResultsThe consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain.ConclusionsThese competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain

Surgical treatment for different forms of hernias in sheep and goats

Sheep and goats are frequently presented with different forms of hernias to veterinary clinics. The aim of this study is to investigate the outcome of the surgical treatment of abdominal, umbilical, inguinal and scrotal hernias in sheep and goats. Fifty-eight clinical cases (sheep = 44, goat = 14) were presented to the Veterinary Teaching Hospital, College of Agriculture and Veterinary Medicine, Qassim University, Saudi Arabia from September, 2003 to September, 2006. These animals had abdominal (sheep = 30, goat = 10), umbilical (sheep = 6, goat = 4), inguinal (sheep = 7) and scrotal (sheep = 1) hernias. All the cases of hernias in sheep and goats were subjected to full study including the history of the case, classification of hernias, the size of the hernial ring, surgical repair of the hernias, adhesions between the hernial sacs in each case, the postoperative care and follow up of the cases. The results revealed that gender had an effect on the incidence of hernia. The incidence of abdominal hernias was higher in females and the incidence of inguinal hernia was higher in males. There was a positive correlation between the history of hernia and the degree of adhesion. For the sheep, 26 out of 30 cases of abdominal hernia had good outcomes and the healing was excellent. There were postoperative complications in 4 ewes. For the goats, there were slight swellings at the site of operation in 2 out of 10 cases of abdominal hernia, while the remaining 8 cases had good outcomes. There was one case of umbilical hernia with an umbilical abscess that had broken down with sepsis formation at the surgical site. In conclusion, the success rates of surgical treatment for all types of hernias were very high and there were no significant differences in the success rates among the different types of hernias in both sheep and goats. The types of suture materials and the types of hernias had no significant effect on the outcome of the surgical treatment

Diabetes status modifies the long-term effect of lipoprotein-associated phospholipase A2 on major coronary events

AIMS/HYPOTHESIS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has an independent prognostic association with major coronary events (MCE). However, no study has investigated whether type 2 diabetes status modifies the effect of Lp-PLA2 activity or inhibition on the risk of MCE. We investigate the interaction between diabetes status and Lp-PLA2 activity with risk of MCE. Subsequently, we test the resulting hypothesis that diabetes status will play a role in modifying the efficacy of an Lp-PLA2 inhibitor. METHODS: A retrospective cohort study design was utilised in two study populations. Discovery analyses were performed in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) cohort based in Scotland, UK. Participants were categorised by type 2 diabetes control status: poorly controlled (HbA1c ≥ 48 mmol/mol or ≥6.5%) and well-controlled (HbA1c < 48 mmol/mol or <6.5%) diabetes (n = 7420). In a secondary analysis of the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial of Lp-PLA2 inhibitor (darapladib) efficacy, 15,828 participants were stratified post hoc by type 2 diabetes diagnosis status (diabetes or no diabetes) at time of recruitment. Lp-PLA2 activity was then divided into population-specific quartiles. MCE were determined from linked medical records in GoDARTS and trial records in STABILITY. First, the interaction between diabetes control status and Lp-PLA2 activity on the outcome of MCE was explored in GoDARTS. The effect was replicated in the placebo arm of STABILITY. The effect of Lp-PLA2 on MCE was then examined in models stratified by diabetes status. This helped determine participants at higher risk. Finally, the effect of Lp-PLA2 inhibition was assessed in STABILITY in the higher risk group. Cox proportional hazards models adjusted for confounders were used to assess associations. RESULTS: In GoDARTS, a significant interaction between increased Lp-PLA2 activity (continuous and quartile divided) and diabetes control status was observed in the prediction of MCE (p < 0.0001). These effects were replicated in the placebo arm of STABILITY (p < 0.0001). In GoDARTS, stratified analyses showed that, among individuals with poorly controlled diabetes, the hazards of MCE for those with high (Q4) Lp-PLA2 activity was 1.19 compared with individuals with lower (Q1-3) Lp-PLA2 activity (95% CI 1.11, 1.38; p < 0.0001) and 1.35 (95% CI 1.16, 1.57; p < 0.0001) when compared with those with the lowest activity (Q1). Those in the higher risk group were identified as individuals with the highest Lp-PLA2 activity (Q4) and poorly controlled diabetes or diabetes. Based on these observations in untreated populations, we hypothesised that the Lp-PLA2 inhibitor would have more benefit in this higher risk group. In this risk group, Lp-PLA2 inhibitor use was associated with a 33% reduction in MCE compared with placebo (HR 0.67 [95% CI 0.50, 0.90]; p = 0.008). In contrast, Lp-PLA2 inhibitor showed no efficacy in individuals with low activity, regardless of diabetes status, or among those with no baseline diabetes and high Lp-PLA2 activity. CONCLUSIONS/INTERPRETATION: These results support the hypothesis that diabetes status modifies the association between Lp-PLA2 activity and MCE. These results suggest that cardiovascular morbidity and mortality associated with Lp-PLA2 activity is especially important in patients with type 2 diabetes, particularly those with worse glycaemic control. Further investigation of the effects of Lp-PLA2 inhibition in diabetes appears warranted. DATA AVAILABILITY: STABILITY trial data are available from clinicaltrials.gov repository through the GlaxoSmithKline clinical study register https://clinicaltrials.gov/ct2/show/NCT00799903 . GoDARTS datasets generated during and/or analysed during the current study are available following request to the GoDARTS Access Managements Group https://godarts.org/scientific-community/