Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels

The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive because its transduction channels open over a very narrow range of displacements. The synchronous gating of transduction channels also underlies the active hair-bundle motility that amplifies and tunes responsiveness. The extent to which the gating of independent transduction channels is coordinated depends on how tightly individual stereocilia are constrained to move as a unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that thermal movements of stereocilia located as far apart as a bundle's opposite edges display high coherence and negligible phase lag. Because the mechanical degrees of freedom of stereocilia are strongly constrained, a force applied anywhere in the hair bundle deflects the structure as a unit. This feature assures the concerted gating of transduction channels that maximizes the sensitivity of mechanoelectrical transduction and enhances the hair bundle's capacity to amplify its inputs.Comment: 24 pages, including 6 figures, published in 200

The effects of temperature on nitrous oxide and oxygen mixture homogeneity and stability

<p>Abstract</p> <p>Background</p> <p>For many long standing practices, the rationale for them is often lost as time passes. This is the situation with respect to the storage and handling of equimolar 50% nitrous oxide and 50% oxygen volume/volume (v/v) mixtures.</p> <p>Methods</p> <p>A review was undertaken of existing literature to examine the developmental history of nitrous oxide and oxygen mixtures for anesthesia and analgesia and to ascertain if sufficient bibliographic data was available to support the position that the contents of a cylinder of a 50%/50% volume/volume (v/v) mixture of nitrous oxide and oxygen is in a homogenous single gas phase in a filled cylinder under normal conditions of handling and storage and if justification could be found for the standard instructions given for handling before use.</p> <p>Results</p> <p>After ranking and removing duplicates, a total of fifteen articles were identified by the various search strategies and formed the basis of this literature review. Several studies were identified that confirmed that 50%/50% v/v mixture of nitrous oxide and oxygen is in a homogenous single gas phase in a filled cylinder under normal conditions of handling and storage. The effect of temperature on the change of phase of the nitrous oxide in this mixture was further examined by several authors. These studies demonstrated that although it is possible to cause condensation and phase separation by cooling the cylinder, by allowing the cylinder to rewarm to room temperature for at least 48 hours, preferably in a horizontal orientation, and inverting it three times before use, the cylinder consistently delivered the proper proportions of the component gases as a homogenous mixture.</p> <p>Conclusions</p> <p>The contents of a cylinder of a 50%/50% volume/volume (v/v) mixture of nitrous oxide and oxygen is in a homogenous single gas phase in a filled cylinder under normal conditions of handling and storage. The standard instructions given for handling before are justified based on previously conducted studies.</p

Understanding the Treatment Algorithm of Patients with Metastatic Pancreatic Neuroendocrine Neoplasms: A Single-Institution Retrospective Analysis Comparing Outcomes of Chemotherapy, Molecular Targeted Therapy, and Peptide Receptor Radionuclide Therapy in 255 Patients

Background The number of therapeutic options for patients with pancreatic neuroendocrine neoplasms (PNEN) has increased, but the optimal therapeutic algorithm has not been defined due to lack of randomised trials comparing different modalities. Methods We performed a retrospective study in patients with metastatic PNEN treated with ≥1 line of systemic therapy. The relationship between baseline characteristics, treatment type and time to treatment failure (TTF), time to progression (TTP) and overall survival (OS) was analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Results Two hundred and fifty-five patients with metastatic PNEN had 491 evaluable lines of therapy. Independent predictors of TTF included treatment type, Ki-67, tumour grade and chromogranin A. To reduce selection bias, a subgroup of 114 patients with grade 2 (G2) metastatic pancreatic neuroendocrine tumours (PNET) was analysed separately. These patients had received 234 lines of treatment (105 chemotherapy, 82 molecular targeted therapy, and 47 peptide receptor radionuclide therapy [PRRT]). In the G2 cohort, TTF and TTP were superior for PRRT compared with both chemotherapy and molecular targeted therapy. OS in the G2 cohort was also superior for those that had received PRRT compared with those that had not (median 84 vs 56 months; HR 0.55, 95%CI 0.31-0.98, p=0.04). Conclusions This study suggests that PRRT is associated with superior clinical outcomes relative to other systemic therapies for G2 metastatic PNET. Prospective studies are required to confirm these observations

Surgical Management of Inguinal Hernias at Bugando Medical Centre in Northwestern Tanzania: Our Experiences in a Resource-Limited Setting.

Inguinal hernia repair remains the commonest operation performed by general surgeons all over the world. There is paucity of published data on surgical management of inguinal hernias in our environment. This study is intended to describe our own experiences in the surgical management of inguinal hernias and compare our results with that reported in literature. A descriptive prospective study was conducted at Bugando Medical Centre in northwestern Tanzania. Ethical approval to conduct the study was obtained from relevant authorities before the commencement of the study. Statistical data analysis was done using SPSS software version 17.0. A total of 452 patients with inguinal hernias were enrolled in the study. The median age of patients was 36 years (range 3 months to 78 years). Males outnumbered females by a ratio of 36.7:1. This gender deference was statistically significant (P=0.003). Most patients (44.7%) presented late (more than five years of onset of hernia). Inguinoscrotal hernia (66.8%) was the commonest presentation. At presentation, 208 (46.0%) patients had reducible hernia, 110 (24.3%) had irreducible hernia, 84 (18.6%) and 50(11.1%) patients had obstructed and strangulated hernias respectively. The majority of patients (53.1%) had right sided inguinal hernia with a right-to-left ratio of 2.1: 1. Ninety-two (20.4%) patients had bilateral inguinal hernias. 296 (65.5%) patients had indirect hernia, 102 (22.6%) had direct hernia and 54 (11.9%) had both indirect and direct types (pantaloon hernia). All patients in this study underwent open herniorrhaphy. The majority of patients (61.5%) underwent elective herniorrhaphy under spinal anaesthesia (69.2%). Local anaesthesia was used in only 1.1% of cases. Bowel resection was required in 15.9% of patients. Modified Bassini's repair (79.9%) was the most common technique of posterior wall repair of the inguinal canal. Lichtenstein mesh repair was used in only one (0.2%) patient. Complication rate was 12.4% and it was significantly higher in emergency herniorrhaphy than in elective herniorrhaphy (P=0.002). The median length of hospital stay was 8 days and it was significantly longer in patients with advanced age, delayed admission, concomitant medical illness, high ASA class, the need for bowel resection and in those with surgical repair performed under general anesthesia (P<0.001). Mortality rate was 9.7%. Longer duration of symptoms, late hospitalization, coexisting disease, high ASA class, delayed operation, the need for bowel resection and presence of complications were found to be predictors of mortality (P<0.001). Inguinal hernias continue to be a source of morbidity and mortality in our centre. Early presentation and elective repair of inguinal hernias is pivotal in order to eliminate the morbidity and mortality associated with this very common problem

Neurosensory symptom complexes after acute mild traumatic brain injury

Mild Traumatic Brain Injury (mTBI) is a prominent public health issue. To date, subjective symptom complaints primarily dictate diagnostic and treatment approaches. As such, the description and qualification of these symptoms in the mTBI patient population is of great value. This manuscript describes the symptoms of mTBI patients as compared to controls in a larger study designed to examine the use of vestibular testing to diagnose mTBI. Five symptom clusters were identified: Post-Traumatic Headache/Migraine, Nausea, Emotional/ Affective, Fatigue/Malaise, and Dizziness/Mild Cognitive Impairment. Our analysis indicates that individuals with mTBI have headache, dizziness, and cognitive dysfunction far out of proportion to those without mTBI. In addition, sleep disorders and emotional issues were significantly more common amongst mTBI patients than non-injured individuals. A simple set of questions inquiring about dizziness, headache, and cognitive issues may provide diagnostic accuracy. The consideration of other symptoms may be critical for providing prognostic value and treatment for best short-term outcomes or prevention of long-term complications

The Cochrane Skin Group: a vanguard for developing and promoting evidence-based dermatology

Aim The Cochrane Skin Group (CSG) is part of the international Cochrane Collaboration (http://www.cochrane.org/). The CSG prepares, maintains and disseminates high quality evidence-based summaries on the prevention, diagnosis and treatment of skin diseases. We present a synopsis of the history, scope and priorities of the CSG. In addition, we report outcomes of CSG reviews and critically assess clinical value. Methods Descriptive analysis of systematic reviews published by the CSG since its inception including output, impact factor, associated methodological studies, and influence in clinical guidelines, promoting patient and public engagement and in triggering new primary research. Results The CSG started in 1997, and has published 61 reviews, 34 protocols and 31 registered titles by August 2013. The CSG scope includes 1000 skin diseases; 80% of reviews cover the top ten diagnoses and 40% of reviews provide clear guidance for clinical practice. CSG reviews had an impact factor of 6.1 in 2011 which places it alongside top dermatology journals. CSG reviews are typically broad in focus and have been shown to be of better quality than non-Cochrane reviews. They are highly cited in clinical guidelines. Several reviews have identified evidence gaps that have led to better primary research. Conclusions The CSG has emerged as a vanguard of evidence-based dermatology by growing a community interested in applying best external evidence to the care of skin patients and by identifying topics for research. CSG reviews are high impact, clinically relevant and have tangibly influenced international dermatology clinical practice guidelines and new research

Managerial Work in a Practice-Embodying Institution - The role of calling, the virtue of constancy

What can be learned from a small scale study of managerial work in a highly marginal and under-researched working community? This paper uses the ‘goods-virtues-practices-institutions’ framework to examine the managerial work of owner-directors of traditional circuses. Inspired by MacIntyre’s arguments for the necessity of a narrative understanding of the virtues, interviews explored how British and Irish circus directors accounted for their working lives. A purposive sample was used to select subjects who had owned and managed traditional touring circuses for at least 15 years, a period in which the economic and reputational fortunes of traditional circuses have suffered badly. This sample enabled the research to examine the self-understanding of people who had, at least on the face of it, exhibited the virtue of constancy. The research contributes to our understanding of the role of the virtues in organizations by presenting evidence of an intimate relationship between the virtue of constancy and a ‘calling’ work orientation. This enhances our understanding of the virtues that are required if management is exercised as a domain-related practice

No straight lines – young women’s perceptions of their mental health and wellbeing during and after pregnancy: a systematic review and meta-ethnography

Background: Young mothers face mental health challenges during and after pregnancy including increased rates of depression compared to older mothers. While the prevention of teenage pregnancy in countries such as the United States and the United Kingdom has been a focus for policy and research in recent decades, the need to understand young women’s own experiences has been highlighted. The aim of this meta-ethnography was to examine young women’s perceptions of their mental health and wellbeing during and after pregnancy to provide new understandings of those experiences. Methods: A systematic review and meta-ethnographic synthesis of qualitative research was conducted. Seven databases were systematically searched and forward and backward searching conducted. Papers were included if they were from Organisation for Economic Co-operation and Development countries and explored mental health and wellbeing experiences of young mothers (age under 20 in pregnancy; under 25 at time of research) as a primary research question – or where evidence about mental health and wellbeing from participants was foregrounded. Nineteen papers were identified and the Critical Appraisal Skills Programme checklist for qualitative research used to appraise the evidence. Following the seven-step process of meta-ethnography, key constructs were examined within each study and then translated into one another. Results: Seven translated themes were identified forming a new line of argument wherein mental health and wellbeing was analysed as relating to individual bodily experiences; tied into past and present relationships; underpinned by economic insecurity and entangled with feelings of societal surveillance. There were ‘no straight lines’ in young women’s experiences, which were more complex than dominant narratives around overcoming adversity suggest. Conclusions: The synthesis concludes that health and social care professionals need to reflect on the operation of power and stigma in young women’s lives and its impact on wellbeing. It adds to understanding of young women’s mental health and wellbeing during and after pregnancy as located in physical and structural factors rather than individual capacities alone

Addressing the Future Burden of Cancer and Its Impact on the Oncology Workforce: Where Is Cancer Prevention and Control?

The need for cancer professionals has never been more urgent than it is today. Reports project serious shortages by 2020 of oncology health care providers. Although many plans have been proposed, no role for prevention has been described. In response, a 2-day symposium was held in 2009 at The University of Texas MD Anderson Cancer Center to capture the current status of the cancer prevention workforce and begin to identify gaps in the workforce. Five working groups were organized around the following topic areas: (a) health policy and advocacy; (b) translation to the community; (c) integrating cancer prevention into clinical practice; (d) health services infrastructure and economics; and (e) discovery, research, and technology. Along with specific recommendations on these topics, the working groups identified two additional major themes: the difficulty of defining areas within the field (including barriers to communication) and lack of sufficient funding. These interdependent issues synergistically impede progress in preventing cancer; they are explored in detail in this synthesis, and recommendations for actions to address them are presented. Progress in cancer prevention should be a major national and international goal. To achieve this goal, ensuring the health of the workforce in cancer prevention and control is imperative

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations