Evidence of Antineutrinos from Distant Reactors Using Pure Water at SNO.

The SNO+ Collaboration reports the first evidence of reactor antineutrinos in a Cherenkov detector. The nearest nuclear reactors are located 240 km away in Ontario, Canada. This analysis uses events with energies lower than in any previous analysis with a large water Cherenkov detector. Two analytical methods are used to distinguish reactor antineutrinos from background events in 190 days of data and yield consistent evidence for antineutrinos with a combined significance of 3.5σ.

Systemic Challenges in Internship Training for Health-Service Psychology: A Call to Action From Trainee Stakeholders.

The challenges observed in health service psychology (HSP) training during COVID-19 revealed systemic and philosophical issues that preexisted the pandemic, but became more visible during the global health crisis. In a position paper written by 23 trainees across different sites and training specializations, the authors use lessons learned from COVID-19 as a touchstone for a call to action in HSP training. Historically, trainee voices have been conspicuously absent from literature about clinical training. We describe longstanding dilemmas in HSP training that were exacerbated by the pandemic and will continue to require resolution after the pandemic has subsided. The authors make recommendations for systems-level changes that would advance equity and sustainability in HSP training. This article advances the conversation about HSP training by including the perspective of trainees as essential stakeholders.

Hormonal Contraceptives and Post-fertilization Effects.

Hormonal contraceptives are widely used for birth control and therapeutic purposes. The mechanism of action proposed for these compounds can be found in several scientific journals published to date. The present work consists in a scoping review of a convenience sample of papers regarding the mechanisms of action of each of the three main classes of hormonal contraceptives available. Different parameters and biological consequences associated with their use were also reviewed. Based on these data, we evaluated the probability of embryo loss due to the use of hormonal contraceptives. Evidence indicates the probability of embryo loss due to post-fertilization effects.

Human cervicovaginal mucus contains an activity that hinders HIV-1 movement.

Cervical and vaginal epithelia are primary barriers against HIV type I (HIV-1) entry during male-to-female transmission. Cervical mucus (CM) is produced by the endocervix and forms a layer locally as well as in the vaginal compartment in the form of cervicovaginal mucus (CVM). To study the potential barrier function of each mucus type during HIV-1 transmission, we quantified HIV-1 mobility in CM and CVM ex vivo using fluorescent microscopy. Virions and 200-nm PEGylated beads were digitally tracked and mean-squared displacement was calculated. The mobility of beads increased significantly in CVM compared with CM, consistent with the known decreased mucin concentration of CVM. Unexpectedly, HIV-1 diffusion was significantly hindered in the same CVM samples in which bead diffusion was unhindered. Inhibition of virus transport was envelope-independent. Our results reveal a previously unknown activity in CVM that is capable of impeding HIV-1 mobility to enhance mucosal barrier function.

Review article: proton pump inhibitors with clopidogrel--evidence for and against a clinically-important interaction.

BACKGROUND: The treatment of acute coronary syndromes involves a combination of antiplatelet therapies. Proton pump inhibitors are frequently recommended for patients receiving clopidogrel in addition to aspirin, to minimise the risk of bleeding. Several studies have shown that proton pump inhibitors can affect the platelet inhibitory effects of clopidogrel. However, the data on whether this has an effect on clinical outcomes are conflicting and a definitive answer is still awaited. AIM: To provide an overview of the evidence for the pharmacological interaction between proton pump inhibitors and clopidogrel and to discuss whether this interaction translates into adverse clinical outcomes. Despite recent developments, clear consensus is lacking. METHODS: A search of the published literature combined with the authors' knowledge of the field. RESULTS: There is evidence to show that proton pump inhibitors can influence the pharmacodynamics of clopidogrel, but the data suggesting clinical effects are weak and conflicting. Supporting a clinically important interaction are four retrospective studies including over 11,000 patients prescribed both clopidogrel and a proton pump inhibitor. Evidence against a clinically important interaction is derived from over 18,000 patients from seven studies, including the only prospective trial to examine the potential interaction. Confounding variables are relevant and prospective clinical evidence is lacking. CONCLUSIONS: Proton pump inhibitors offer clear protection and the concern over clinically relevant interactions with clopidogrel is biologically plausible, but not yet proven.

Effects of prasterone (dehydroepiandrosterone) on markers of cardiovascular risk and bone turnover in premenopausal women with systemic lupus erythematosus: a pilot study.

DHEA (dehydroepiandrosterone) is a weak androgen with proposed efficacy in the treatment of mild to moderate lupus, and possible beneficial effects on cardiovascular risk and bone mineral density. We hypothesized that treatment with 200 mg a day of Prasterone (DHEA) would improve pre-clinical measures of atherosclerosis: flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NMD), and circulating apoptotic endothelial cells (CD 146(AnnV +)), as well markers of bone metabolism. Thirteen premenopausal female patients with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)

Enhanced cellular responses and environmental sampling within inner foreskin explants: implications for the foreskin's role in HIV transmission.

The decrease in HIV acquisition after circumcision suggests a role for the foreskin in HIV transmission. However, the mechanism leading to protection remains undefined. Using tissue explant cultures we found that Langerhans cells (LCs) in foreskin alter their cellular protein expression in response to external stimuli. Furthermore, we observe that upon treatment with TNF-alpha, tissue-resident LCs became activated and that stimulatory cytokines can specifically cause an influx of CD4+ T-cells into the epithelial layer. Importantly, both of these changes are significant in the inner, but not outer, foreskin. In addition, we find that LCs in the inner foreskin have increased ability to sample environmental proteins. These results suggest differences in permeability between the inner and outer foreskin and indicate that HIV target cells in the inner foreskin have increased interaction with external factors. This increased responsiveness and sampling provides novel insights into the underlying mechanism of how circumcision can decrease HIV transmission.

Can a clinical prediction tool guide HIV-testing decisions? Experience at a national hospital in Guatemala.

The USA and international recommendations no longer emphasize using risk factors to target groups for HIV-testing. Using a Guatemalan database of HIV tests, we developed a clinical prediction rule to guide decisions on HIV-testing. Prior to HIV-testing, data were collected on demographics, risk factors and prior testing. Based on a theoretical construct incorporating demographics, known HIV risk factors and symptoms, we developed a logistic regression model to predict HIV seropositivity. Between 2000 and 2005, 16,471 tests were performed, of which 19.8% were positive. The algorithm successfully predicted 1883 of 2489 HIV-positive tests (sensitivity 76%, likelihood ratio [LR]-positive 2.45) and 6282 of 9086 HIV-negative tests (specificity 69%, LR-negative 0.35). Although the model indices are robust, applying the model in a clinical setting would have little impact on improving selective testing practices. Our findings support current recommendations for universal HIV-testing, not selective testing based on risk factors. Before these recommendations can be adopted widely in Guatemala, treatment access needs to be assured and protections put in place for people diagnosed with HIV infection.

PCB concentrations in lake trout (Salvelinus namaycush) are correlated to habitat use and lake characteristics.

This study considers the importance of lake trout habitat as a factor determining persistent organochlorine (OC) concentration. Lake trout is a stenothermal, cold water species and sensitive to hypoxia. Thus, factors such as lake depth, thermal stratification, and phosphorus enrichment may determine not only which lakes can support lake trout but may also influence among-lake variability in lake trout population characteristics including bioaccumulation of OCs. A survey of 23 lakes spanning much of the natural latitudinal distribution of lake trout provided a range of lake trout habitat to test the hypothesis that lake trout with greater access to littoral habitat for feeding will have lower concentrations of OCs than lake trout that are more restricted to pelagic habitat. Using the delta13C stable isotope signature in lake trout as an indicator of influence of benthic littoral feeding, we found a negative correlation between lipid-corrected delta13C and sigmaPCB concentrations supporting the hypothesis that increasing accessto littoral habitat results in lower OCs in lake trout. The prominence of mixotrophic phytoplankton in lakes with more contaminated lake trout indicated the pelagic microbial food web may exacerbate the biomagnification of OCs when lake trout are restricted to pelagic feeding. A model that predicted sigmaPCB in lake trout based on lake area and latitude (used as proximate variables for proportion of littoral versus pelagic habitat and accessibility to littoral habitat respectively) explained 73% of the variability in sigmaPCBs in lake trout in the 23 lakes surveyed.

The metabolic marker tumour pyruvate kinase type M2 (tumour M2-PK) shows increased expression along the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's oesophagus.

BACKGROUND: Proliferating and tumour cells express the glycolytic isoenzyme, pyruvate kinase type M2 (M2-PK). In tumours cells, M2-PK usually exists in dimeric form (tumour M2-PK), causing the accumulation of glycolytic phosphometabolites, which allows cells to invade areas with low oxygen and glucose concentrations. AIMS: To investigate the expression of tumour M2-PK during the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus, and to assess the prognostic usefulness of tumour M2-PK in oesophageal cancer. MATERIALS/METHODS: One hundred and ninety cases selected from the histopathology archives as follows: 17 reflux oesophagitis, 37 Barrett's oesophagus, 21 high grade dysplasia, 112 adenocarcinomas, and three control tumours. Sections were stained immunohistochemically with antibody to tumour M2-PK. RESULTS: Tumour M2-PK was expressed in all cases, and increased cytoplasmic expression was seen with progression along the metaplasia-dysplasia-adenocarcinoma sequence. All cases of adenocarcinoma showed 100% staining so that tumour M2-PK was not a useful prognostic marker. CONCLUSIONS: Tumour M2-PK is not a specific marker of Barrett's adenocarcinoma, but may be important as a marker of transformed and highly proliferating clones during progression along the metaplasia-dysplasia-adenocarcinoma sequence.

The role of receptor tyrosine kinase inhibition in treating gastrointestinal malignancy.

Tyrosine kinase receptors are proteins that transduce the signal from many growth factor and cytokine ligands to produce intracellular responses. As such they can activate multiple signalling cascade pathways and influence cell division, migration and survival. Many show upregulation in certain malignancies, including those of the gastrointestinal tract, and are thought to play key roles in carcinogenesis. This makes them attractive targets for drug therapy and in recent years many inhibitors have been developed. This review discusses the current situation regarding the development of inhibitors with particular reference to the erbB family, the insulin-like growth factor receptor, the Met receptor, the receptor for vascular endothelial growth factor and the Kit receptor. The evidence will be related back to cancers of the gut lumen. Clinical effectiveness in this area seems to lie in using a combinatorial approach that inhibits multiple key signalling points, and the reasons for this will be discussed.

The treatment, management and prevention of oesophageal cancer.

The combination of a rising incidence and a poor survival rate makes oesophageal cancer a major health issue. Adenocarcinoma of the oesophagus is associated with one of the commonest pre-malignant lesions recognised, Barrett's metaplasia. This provides a focus for early detection and intervention. The subjects of acid suppression, bile reflux, COX-2 inhibition and ablation therapy will be discussed herewith. Established carcinoma is now rarely treated by surgery alone and this review discusses the benefits of multimodality therapy combined with more accurate staging techniques. Finally an emerging understanding of the molecular events that characterise the transition to carcinoma may provide novel targets in cancer therapy such as epidermal growth factor receptor (EGFR) and TNF-alpha. This review will focus on some of the future developments in the treatment of oesophageal cancer.

Respiratory support of the head-injured child.

Meticulous care of the head-injured child revolves around the prevention of secondary injury. In no arena is this more crucial than in the respiratory support of the pediatric traumatic brain-injured patient. Careful attention to intubation techniques, maintenance of adequate oxygen delivery, avoidance of hypoxia, and judicious use of PEEP and other respiratory therapeutics all can be invaluable in the care of the pediatric traumatic brain-injured patient and may ultimately enhance outcome in this sometimes devastating disease.

Sex-role strain in alcoholic women.

We investigated sources of sex-role strain between alcoholic and non-alcoholic women. We compared alcoholic (n = 55) and non-alcoholic (n = 51) women on the presence of strain in their sex-role identity and strain between sex-role identity, attitudes, and behaviors in 1996. One source of sex-role strain for alcoholic women was the discrepancy between their perceived femininity when intoxicated versus when sober. A second source of strain for alcoholic women was the discrepancy between their traditionally feminine sex-role identity as well as attitudes toward marital, parental, and educational roles and their participation in male-valued activities. We offer suggestions for future research.

The role of race in the clinical presentation.

What role, if any, should race play in clinical presentations? While race is widely used as a way of identifying patients, this practice has been challenged as conceptually flawed, potentially misleading, and possibly prejudicial to the patient. There are, however; important reasons for not excluding information about race. This article includes a set of guidelines for the inclusion of racial data in presentations: (1) Race is a social construct and, if used, should be recorded in the social history, not the opening sentence of the presentation. (2) Patients should self-identity their race or races. (3) Race should not be used as a proxy for genetic variation, social class, or other elements of the social history. (4) Clinicians should be mindful of the potential influence of racism in the clinical encounter.

Baseline metal concentrations in coastal Labrador sediments.

Levels of Cr, Cu, Fe, Pb, Ni, and Zn in surface sediment from the Voisey's Bay area of coastal Labrador showed no evidence of recent anthropogenic input of metals. Metal concentrations in surface sediments, normalized to Li, fell within the 95% confidence limits of the background levels. Further analysis showed that the Li-metal regression lines from the surface sediments and sediments from 30-cm depth had the same slope and intercepts, suggesting that there was no difference in the metal content of the sediments at the two depths. Li-metal relationships can be used as a measure of the natural variability of the metal concentrations for the region and will serve as a baseline against which future anthropogenic affects may be assessed.

Staphylococcal enterotoxin-B-induced lethal shock in mice is T-cell-dependent, but disease susceptibility is defined by the non-T-cell compartment.

Here we introduce a murine model for SEB-induced lethal shock that relies on the administration of SEB alone and does not involve hepatotoxicity by avoiding pretreatment with the hepatotoxin D-galactosamine. In the absence of D-gal, we first identified SEB-susceptible and -resistant H-2(k)-congenic mouse strains. In contrast with what is well established for the classic D-gal-dependent model and what therefore is anticipated for the human disease, the levels of TNF produced did not define susceptibility in our model. The SEB-induced TNF response in vitro and in vivo was stronger in resistant B10.BR mice than in susceptible C3H/HeJ mice. Neither the magnitude nor the quality of the T cell response induced by SEB defined susceptibility. Adoptive transfer experiments in C3H-SCID recipient mice demonstrated that induction of the disease is T-cell-dependent. T cells from resistant and susceptible mice both transferred disease susceptibility to H-2(k)-congenic C3H-SCID mice, indicating that disease susceptibility is downstream from T cell activation, at the level of the target organ itself, which responds differently to T-cell-induced inflammation.

Direct comparison of the impact of head tracking, reverberation, and individualized head-related transfer functions on the spatial perception of a virtual speech source.

A study of sound localization performance was conducted using headphone-delivered virtual speech stimuli, rendered via HRTF-based acoustic auralization software and hardware, and blocked-meatus HRTF measurements. The independent variables were chosen to evaluate commonly held assumptions in the literature regarding improved localization: inclusion of head tracking, individualized HRTFs, and early and diffuse reflections. Significant effects were found for azimuth and elevation error, reversal rates, and externalization.