Identification of sex hormone-binding globulin in the human hypothalamus

Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin ( SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. Copyright (c) 2005 S. Karger AG, Base

Causes of Higher Climate Sensitivity in CMIP6 Models

Equilibrium climate sensitivity, the global surface temperature response to CO urn:x-wiley:grl:media:grl60047:grl60047-math-0001 doubling, has been persistently uncertain. Recent consensus places it likely within 1.5–4.5 K. Global climate models (GCMs), which attempt to represent all relevant physical processes, provide the most direct means of estimating climate sensitivity via CO urn:x-wiley:grl:media:grl60047:grl60047-math-0002 quadrupling experiments. Here we show that the closely related effective climate sensitivity has increased substantially in Coupled Model Intercomparison Project phase 6 (CMIP6), with values spanning 1.8–5.6 K across 27 GCMs and exceeding 4.5 K in 10 of them. This (statistically insignificant) increase is primarily due to stronger positive cloud feedbacks from decreasing extratropical low cloud coverage and albedo. Both of these are tied to the physical representation of clouds which in CMIP6 models lead to weaker responses of extratropical low cloud cover and water content to unforced variations in surface temperature. Establishing the plausibility of these higher sensitivity models is imperative given their implied societal ramifications

The Effect of Arsenic Mitigation Interventions on Disease Burden in Bangladesh

Many interventions have been advocated to mitigate the impact of arsenic contamination of drinking water in Bangladesh. However, there are few data on the true magnitude of arsenic-related disease in Bangladesh nationally. There has also been little consideration given to possible adverse effects of such interventions, in particular, diarrheal disease. The purpose of this study was to estimate and compare the likely impacts of arsenic mitigation interventions on both arsenic-related disease and water-borne infectious disease. We found that arsenic-related disease currently results in 9,136 deaths per year and 174,174 disability-adjusted life years (DALYs; undiscounted) lost per year in those exposed to arsenic concentrations > 50 μg/L. This constitutes 0.3% of the total disease burden in Bangladesh in terms of undiscounted DALYs. We found intervention to be of overall benefit in reducing disease burden in most scenarios examined, but the concomitant increase in water-related infectious disease significantly reduced the potential benefits gained from intervention. A minimum reduction in arsenic-related DALYs of 77% was necessary before intervention achieved any reduction in net disease burden. This is assuming that interventions were provided to those exposed to > 50 μg/L and would concomitantly result in a 20% increase in water-related infectious disease in those without access to adequate sanitation. Intervention appears to be justified for those populations exposed to high levels of arsenic, but it must be based on exposure levels and on the effectiveness of interventions not only in reducing arsenic but in minimizing risk of water-related infections

Reflexive learning, socio-cognitive conflict and peer-assessment to improve the quality of feedbacks in online tests

International audienceOur previous works have introduced the Tsaap-notes platform dedicated to the semi automatic generation of multiple choice questionnaire providing feedbacks: it reuses interactive questions asked by teachers during lectures, as well as the notes taken by students after the presentation of the results as feedbacks integrated into the quizzes. In this paper, we introduce a new feature which aims at increasing the number of contributions of students in order to significantly improve the quality of the feedbacks used in the resulting quizzes. This feature splits the submission of an answer into several distinct phases to harvest explanations given by students, and then applies an algorithm to filter the best contributions to be integrated as feedbacks in the tests. Our approach has been validated by a first experimentation involving master students enrolled in a computer science course

On the unification of dwarf and giant elliptical galaxies

The near orthogonal distributions of dwarf elliptical (dE) and giant elliptical (E) galaxies in the mu_e-Mag and mu_e-log(R_e) diagrams have been interpreted as evidence for two distinct galaxy formation processes. However, continuous, linear relationships across the alleged dE/E boundary at M_B = -18 mag - such as those between central surface brightness (mu_0) and (i) galaxy magnitude and (ii) light-profile shape (n) - suggest a similar, governing formation mechanism. Here we explain how these latter two linear trends necessitate a different behavior for dE and E galaxies, exactly as observed, in diagrams involving mu_e (and also _e). A natural consequence is that the distribution of dEs and Es in Fundamental Plane type analyses that use the associated intensity I_e, or _e, are expected to appear different. Together with other linear trends across the alleged dE/E boundary, such as those between luminosity and color, metallicity, and velocity dispersion, it appears that the dEs form a continuous extension to the E galaxies. The presence of partially depleted cores in luminous (M_B < -20.5 mag) Es does however signify the action of a different physical process at the centers (< ~300 pc) of these galaxies.Comment: 5 pages from the proceedings of the 2004 conference "Penetrating bars through masks of cosmic dust: the Hubble tuning fork strikes a new note". Edited by D. L. Block, I. Puerari, K. C. Freeman, R. Groess, and E. K. Bloc

The relationship between cadence, pedalling technique and gross efficiency in cycling

Technique and energy saving are two variables often considered as important for performance in cycling and related to each other. Theoretically, excellent pedalling technique should give high gross efficiency (GE). The purpose of the present study was to examine the relationship between pedalling technique and GE. 10 well-trained cyclists were measured for GE, force effectiveness (FE) and dead centre size (DC) at a work rate corresponding to ~75% of VO2max during level and inclined cycling, seat adjusted forward and backward, at three different cadences around their own freely chosen cadence (FCC) on an ergometer. Within subjects, FE, DC and GE decreased as cadence increased (p < 0.001). A strong relationship between FE and GE was found, which was to great extent explained by FCC. The relationship between cadence and both FE and GE, within and between subjects, was very similar, irrespective of FCC. There was no difference between level and inclined cycling position. The seat adjustments did not affect FE, DC and GE or the relationship between them. Energy expenditure is strongly coupled to cadence, but force effectiveness, as a measure for pedalling technique, is not likely the cause of this relationship. FE, DC and GE are not affected by body orientation or seat adjustments, indicating that these parameters and the relationship between them are robust to coordinative challenges within a range of cadence, body orientation and seat position that is used in regular cycling

Clinical outcome of endonasal KTP laser assisted dacryocystorhinostomy

BACKGROUND: To evaluate the clinical outcome of primary endonasal laser assisted dacryocystorhinostomy (ENL-DCR) using the potassium-titanyl-phosphate laser. METHODS: We retrospectively reviewed all primary ENL-DCRs performed within a period of twelve months by the same combined Ophthalmology and Otorhinolaringology team in Freeman Hospital, Newcastle upon Tyne, UK. The main outcome measure for success was resolution or significant improvement of epiphora. Details of surgery, intraoperative and postoperative complications, as well as pathology associated with failure were also studied. Patients were followed up for at least 12 months. RESULTS: A total of 41 consecutive ENL-DCRs on 29 patients (22 females, 7 males, mean age 75 years) were analysed. All patients had bicanalicular silicone intubation for at least 4 months. The success rate at 12 months postoperatively was 78.1%. Pathology associated with failure included: intranasal pathology (12.2%), mucocele (7.3%), and systemic sarcoidosis (2.4%). No significant intra-operative complications were recorded. CONCLUSION: The ENL-DCR with potassium-titanyl-phosphate laser can be considered as a safe and efficient primary procedure for the treatment of nasolacrimal duct obstruction

Transdermal fentanyl for the treatment of pain caused by osteoarthritis of the knee or hip: an open, multicentre study

BACKGROUND: This study was designed to evaluate the utility of transdermal fentanyl (TDF, Durogesic(®)) for the treatment of pain due to osteoarthritis (OA) of the knee or hip, which was not adequately controlled by non-opioid analgesics or weak opioids. The second part of the trial, investigating TDF in patients with rheumatoid arthritis (RA) is reported separately. METHODS: Current analgesia was optimised during a 1-week run-in. Patients then received 28 days treatment with TDF starting at 25 μg/hr, with the option to increase the dose until adequate pain control was achieved. Metoclopramide was taken during the first week and then as needed. RESULTS: Of the 159 patients recruited, 75 with OA knee and 44 with OA hip completed the treatment phase, 30 knee and 18 hip patients entered the one-week taper-off phase. The most frequently used maximum dose of TDF was 25 μg/hr. The number of patients with adequate pain control increased during the run-in period from 4% to 27%, and further increased during TDF treatment to 88% on day 28. From baseline to endpoint, there were significant reductions in pain (p < 0.001) and improvements in functioning (p < 0.001) and physical (p < 0.001) and mental (p < 0.05) health. Scores for 'pain right now' decreased significantly within 24 hours of starting TDF treatment. TDF was assessed favourably and 84% of patients would recommend it for OA-related pain. Nausea and vomiting were the most common adverse events (reported by 32% and 26% of patients respectively), despite prophylaxis with metoclopramide, which showed limited efficacy in this setting. CONCLUSION: TDF significantly increased pain control, and improved functioning and quality of life. Metoclopramide appeared to be of limited value in preventing nausea and vomiting; more effective anti-emetic treatment may enable more people to benefit from strong opioids such as TDF. This study suggests that four weeks is a reasonable period to test the benefit of adding TDF to improve pain control in OA patients and that discontinuing therapy in cases of limited benefit creates no major obstacles