Acute intracerebral haemorrhage: diagnosis and management

Intracerebral haemorrhage (ICH) accounts for half of the disability-adjusted life years lost due to stroke worldwide. Care pathways for acute stroke result in the rapid identification of ICH, but its acute management can prove challenging because no individual treatment has been shown definitively to improve its outcome. Nonetheless, acute stroke unit care improves outcome after ICH, patients benefit from interventions to prevent complications, acute blood pressure lowering appears safe and might have a modest benefit, and implementing a bundle of high-quality acute care is associated with a greater chance of survival. In this article, we address the important questions that neurologists face in the diagnosis and acute management of ICH, and focus on the supporting evidence and practical delivery for the main acute interventions

Social stigma and executive compensation

We document that executives working at firms perceived negatively in light of social norms, such as tobacco, gambling and alcohol, earn a significant compensation premium. The premium compensates for personal costs executives bear due to their employer’s negative public perception and include: (i) a reduced likelihood these CEOs will serve as directors on other firms’ boards, which associates with lower executives’ social status, and (ii) impaired job mobility as employers shun stigmatized executives. The compensation premium is not explained by higher managerial skill required in firms we investigate, higher employment contract risk, political capital, litigation risk, or differences in corporate governance quality, and robust to endogeneity concerns. Our results highlight the significant impact job-related social stigma has on executive compensation

Highly Conserved Non-Coding Sequences Are Associated with Vertebrate Development

In addition to protein coding sequence, the human genome contains a significant amount of regulatory DNA, the identification of which is proving somewhat recalcitrant to both in silico and functional methods. An approach that has been used with some success is comparative sequence analysis, whereby equivalent genomic regions from different organisms are compared in order to identify both similarities and differences. In general, similarities in sequence between highly divergent organisms imply functional constraint. We have used a whole-genome comparison between humans and the pufferfish, Fugu rubripes, to identify nearly 1,400 highly conserved non-coding sequences. Given the evolutionary divergence between these species, it is likely that these sequences are found in, and furthermore are essential to, all vertebrates. Most, and possibly all, of these sequences are located in and around genes that act as developmental regulators. Some of these sequences are over 90% identical across more than 500 bases, being more highly conserved than coding sequence between these two species. Despite this, we cannot find any similar sequences in invertebrate genomes. In order to begin to functionally test this set of sequences, we have used a rapid in vivo assay system using zebrafish embryos that allows tissue-specific enhancer activity to be identified. Functional data is presented for highly conserved non-coding sequences associated with four unrelated developmental regulators (SOX21, PAX6, HLXB9, and SHH), in order to demonstrate the suitability of this screen to a wide range of genes and expression patterns. Of 25 sequence elements tested around these four genes, 23 show significant enhancer activity in one or more tissues. We have identified a set of non-coding sequences that are highly conserved throughout vertebrates. They are found in clusters across the human genome, principally around genes that are implicated in the regulation of development, including many transcription factors. These highly conserved non-coding sequences are likely to form part of the genomic circuitry that uniquely defines vertebrate development

Inference of the infection status of individuals using longitudinal testing data from cryptic populations: Towards a probabilistic approach to diagnosis

Effective control of many diseases requires the accurate detection of infected individuals. Confidently ascertaining whether an individual is infected can be challenging when diagnostic tests are imperfect and when some individuals go for long periods of time without being observed or sampled. Here, we use a multi-event capture-recapture approach to model imperfect observations of true epidemiological states. We describe a method for interpreting potentially disparate results from individuals sampled multiple times over an extended period, using empirical data from a wild badger population naturally infected with Mycobacterium bovis as an example. We examine the effect of sex, capture history and current and historical diagnostic test results on the probability of being truly infected, given any combination of diagnostic test results. In doing so, we move diagnosis away from the traditional binary classification of apparently infected versus uninfected to a probability-based interpretation which is updated each time an individual is re-sampled. Our findings identified temporal variation in infection status and suggest that capture probability is influenced by year, season and infection status. This novel approach to combining ecological and epidemiological data may aid disease management decision-making by providing a framework for the integration of multiple diagnostic test data with other information

Effects of Hylan G-F 20 supplementation on cartilage preservation detected by magnetic resonance imaging in osteoarthritis of the knee: a two-year single-blind clinical trial

<p>Abstract</p> <p>Background</p> <p>Although viscosupplementation is an effective symptomatic treatment for knee osteoarthritis (OA), the effect of longer term administration on articular cartilage has not been fully explored. We examined the effect of viscosupplementation with Hylan G-F 20 on knee cartilage over 2 years in patients with knee OA.</p> <p>Methods</p> <p>In this prospective, single-blind, parallel control group pilot study, 78 patients with symptomatic knee OA (Kellgren-Lawrence grade II and III) were assigned to either intervention group (n = 39 receiving 4 courses of 3 × 2.0 ml of intra-articular Hylan G-F 20 injections at 6 month intervals) or control group (n = 39 receiving usual care for knee OA without injections). Magnetic resonance imaging of the study knee was performed at baseline, 12 and 24 months. Cartilage volume and defects were assessed using validated methods.</p> <p>Results</p> <p>Fifty-five subjects (71%) completed 24 month follow up. Over 24 months, the intervention group had a reduced annual percentage rate of medial and lateral tibial cartilage volume loss (mean ± SD, -0.3 ± 2.7% and -1.4 ± 4.3%) compared with the control group (2.3 ± 2.6% and 1.4 ± 2.6%, P = 0.001 and 0.005 for difference, respectively). The intervention group also showed reduced cartilage defect score increment in the medial tibiofemoral compartment (0.1 ± 1.3) compared with the control group (0.8 ± 1.5, P = 0.05).</p> <p>Conclusions</p> <p>Six monthly intra-articular injections of Hylan G-F 20 administered to patients with symptomatic knee OA have a beneficial effect on knee cartilage preservation measured by both cartilage volume and cartilage defects. Hylan G-F 20 warrants further evaluation in larger clinical trials as a possible disease-modifying agent in the treatment of knee OA.</p> <p>Trial Registration</p> <p>The study was registered with ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00393393">NCT00393393</a>).</p

Explicit and implicit information needs of people with depression: a qualitative investigation of problems reported on an online depression support forum

<p>Abstract</p> <p>Background</p> <p>Health management is impeded when consumers do not possess adequate knowledge about their illness. At a public health level, consumer knowledge about depression is particularly important because depression is highly prevalent and causes substantial disability and burden. However, currently little is known about the information needs of people with depression. This study aimed to investigate the explicit and implicit information needs of users of an online depression support forum.</p> <p>Methods</p> <p>A sample of 2680 posts was systematically selected from three discussion forums on an online depression bulletin board (blueboard.anu.edu.au). Data were examined for evidence of requests for information (reflecting explicit needs) and reports of past or current problems (implicit needs). Thematic analysis was conducted using a data-driven inductive approach with the assistance of NVivo 7, and instances of questions and people reporting particular types of problems were recorded.</p> <p>Results</p> <p>A total of 134 participants with personal experience of depression contributed to the data analysed. Six broad themes represented participant queries and reported problems: Understanding depression; disclosure and stigma; medication; treatment and services; coping with depression; and comorbid health problems. A variety of specific needs were evident within these broad thematic areas. Some people (n = 46) expressed their information needs by asking direct questions (47 queries) but the majority of needs were expressed implicitly (351 problems) by the 134 participants. The most evident need for information related to coping with depression and its consequences, followed by topics associated with medication, treatment and services.</p> <p>Conclusions</p> <p>People with depression have substantial unmet information needs and require strategies to deal with the difficulties they face. They require access to high quality and relevant online resources and professionals; thus, there is a need to rectify current gaps in the provision of information and limitations of dissemination. Greater knowledge about depression and its treatment is also needed at the general community level.</p

Small global-mean cooling due to volcanic radiative forcing

In both the observational record and atmosphere-ocean general circulation model (AOGCM) simulations of the last ∼∼ 150 years, short-lived negative radiative forcing due to volcanic aerosol, following explosive eruptions, causes sudden global-mean cooling of up to ∼∼ 0.3 K. This is about five times smaller than expected from the transient climate response parameter (TCRP, K of global-mean surface air temperature change per W m−2 of radiative forcing increase) evaluated under atmospheric CO2 concentration increasing at 1 % yr−1. Using the step model (Good et al. in Geophys Res Lett 38:L01703, 2011. doi:10.​1029/​2010GL045208), we confirm the previous finding (Held et al. in J Clim 23:2418–2427, 2010. doi:10.​1175/​2009JCLI3466.​1) that the main reason for the discrepancy is the damping of the response to short-lived forcing by the thermal inertia of the upper ocean. Although the step model includes this effect, it still overestimates the volcanic cooling simulated by AOGCMs by about 60 %. We show that this remaining discrepancy can be explained by the magnitude of the volcanic forcing, which may be smaller in AOGCMs (by 30 % for the HadCM3 AOGCM) than in off-line calculations that do not account for rapid cloud adjustment, and the climate sensitivity parameter, which may be smaller than for increasing CO2 (40 % smaller than for 4 × CO2 in HadCM3)

NMDA Receptor Stimulation Induces Reversible Fission of the Neuronal Endoplasmic Reticulum

With few exceptions the endoplasmic reticulum (ER) is considered a continuous system of endomembranes within which proteins and ions can move. We have studied dynamic structural changes of the ER in hippocampal neurons in primary culture and organotypic slices. Fluorescence recovery after photobleaching (FRAP) was used to quantify and model ER structural dynamics. Ultrastructure was assessed by electron microscopy. In live cell imaging experiments we found that, under basal conditions, the ER of neuronal soma and dendrites was continuous. The smooth and uninterrupted appearance of the ER changed dramatically after glutamate stimulation. The ER fragmented into isolated vesicles in a rapid fission reaction that occurred prior to overt signs of neuronal damage. ER fission was found to be independent of ER calcium levels. Apart from glutamate, the calcium ionophore ionomycin was able to induce ER fission. The N-methyl, D-aspartate (NMDA) receptor antagonist MK-801 inhibited ER fission induced by glutamate as well as by ionomycin. Fission was not blocked by either ifenprodil or kinase inhibitors. Interestingly, sub-lethal NMDA receptor stimulation caused rapid ER fission followed by fusion. Hence, ER fission is not strictly associated with cellular damage or death. Our results thus demonstrate that neuronal ER structure is dynamically regulated with important consequences for protein mobility and ER luminal calcium tunneling

The management and outcome for patients with chronic subdural hematoma: a prospective, multicenter, observational cohort study in the United Kingdom

Symptomatic chronic subdural hematoma (CSDH) will become an increasingly common presentation in neurosurgical practice as the population ages, but quality evidence is still lacking to guide the optimal management for these patients. The British Neurosurgical Trainee Research Collaborative (BNTRC) was established by neurosurgical trainees in 2012 to improve research by combining the efforts of trainees in each of the United Kingdom (UK) and Ireland's neurosurgical units (NSUs). The authors present the first study by the BNTRC that describes current management and outcomes for patients with CSDH throughout the UK and Ireland. This provides a resource both for current clinical practice and future clinical research on CSDH

Pig farmers’ willingness to pay for management strategies to reduce aggression between pigs

When deciding whether to invest in an improvement to animal welfare, farmers must trade-off the relative costs and benefits. Despite the existence of effective solutions to many animal welfare issues, farmers’ willingness to pay for them is largely unknown. This study modelled pig farmers’ decisions to improve animal welfare using a discrete choice experiment focused on alleviating aggression between growing/finishing pigs at regrouping. Eighty-two UK and Irish pig farm owners and managers were asked to choose between hypothetical aggression control strategies described in terms of four attributes; installation cost, on-going cost, impact on skin lesions from aggression and impact on growth rate. If they did not like any of the strategies they could opt to keep their current farm practice. Systematic variations in product attributes allowed farmers’ preferences and willingness to pay to be estimated and latent class modelling accounted for heterogeneity in responses. The overall willingness to pay to reduce lesions was low at £0.06 per pig place (installation cost) and £0.01 per pig produced (running cost) for each 1% reduction in lesions. Results revealed three independent classes of farmers. Farmers in Class 1 were unlikely to regroup unfamiliar growing/finishing pigs, and thus were unwilling to adopt measures to reduce aggression at regrouping. Farmers in Classes 2 and 3 were willing to adopt measures providing certain pre-conditions were met. Farmers in Class 2 were motivated mainly by business goals, whilst farmers in Class 3 were motivated by both business and animal welfare goals, and were willing to pay the most to reduce aggression; £0.11 per pig place and £0.03 per pig produced for each 1% reduction in lesions. Farmers should not be considered a homogeneous group regarding the adoption of animal welfare innovations. Instead, campaigns should be targeted at subgroups according to their independent preferences and willingness to pay