The Complex Dance of Organelles during Mitochondrial Division.

Mitochondria are dynamic organelles that undergo cycles of fission and fusion events depending on cellular requirements. During mitochondrial division, the GTPase dynamin-related protein-1 is recruited to endoplasmic reticulum (ER)-induced mitochondrial constriction sites where it drives fission. However, the events required to complete scission of mitochondrial membranes are not well understood. Here, we emphasize the recently described roles for Golgi-derived phosphatidylinositol 4-phosphate (PI4P)-containing vesicles in the last steps of mitochondrial division. We then propose how trans-Golgi network vesicles at mitochondria-ER contact sites and PI4P generation could mechanistically execute mitochondrial division, by recruiting PI4P effectors and/or the actin nucleation machinery. Finally, we speculate on mechanisms to explain why such a complex dance of different organelles is required to facilitate the remodelling of mitochondrial membranes

Imposter Phenomenon and Research Experiences Among Counselor Educators

Content analysis was employed to explore research experiences and imposter phenomenon (IP) among 25 counselor educators. Six overarching categories emerged including inconsistent areas of efficacy in the research process, supports in conducting research, barriers in conducting research, experiences of IP across roles, triggers of IP, and factors that quiet IP, with implications for counselor educators

Surveillance of Transmitted HIV-1 Drug Resistance in Gauteng and KwaZulu-Natal Provinces, South Africa, 2005-2009

Surveillance of human immunodeficiency virus type 1 transmitted drug resistance (TDR) was conducted among pregnant women in South Africa over a 5-year period after the initiation of a large national antiretroviral treatment program. Analysis of TDR data from 9 surveys conducted between 2005 and 2009 in 2 provinces of South Africa suggests that while TDR remains low (<5%) in Gauteng Province, it may be increasing in KwaZulu-Natal, with the most recent survey showing moderate (5%-15%) levels of resistance to the nonnucleoside reverse transcriptase inhibitor drug clas

Does backreaction enforce the averaged null energy condition in semiclassical gravity?

The expected stress-energy tensor of quantum fields generically violates the local positive energy conditions of general relativity. However, may satisfy some nonlocal conditions such as the averaged null energy condition (ANEC), which would rule out traversable wormholes. Although ANEC holds in Minkowski spacetime, it can be violated in curved spacetimes if one is allowed to choose the spacetime and quantum state arbitrarily, without imposition of the semiclassical Einstein equation G_{ab} = 8 \pi . In this paper we investigate whether ANEC holds for solutions to this equation, by studying a free, massless scalar field with arbitrary curvature coupling in perturbation theory to second order about the flat spacetime/vacuum solution. We "reduce the order" of the perturbation equations to eliminate spurious solutions, and consider the limit in which the lengthscales determined by the incoming state are much larger than the Planck length. We also need to assume that incoming classical gravitational radiation does not dominate the first order metric perturbation. We find that although the ANEC integral can be negative, if we average the ANEC integral transverse to the geodesic with a suitable Planck scale smearing function, then a strictly positive result is obtained in all cases except for the flat spacetime/vacuum solution. This result suggests --- in agreement with conclusions drawn by Ford and Roman from entirely independent arguments --- that if traversable wormholes do exist as solutions to the semiclassical equations, they cannot be macroscopic but must be ``Planck scale''. A large portion of our paper is devoted to the analysis of general issues concerning the nature of the semiclassical Einstein equation and of prescriptions for extracting physically relevant solutions.Comment: 54 pages, 3 figures, uses revtex macros and epsf.tex, to appear in Phys Rev D. A new appendix has been added showing consistency of our results with recent results of Visser [gr-qc/9604008]. Some corrections were made to Appendix A, and several other minor changes to the body of the paper also were mad

Of Some Theoretical Significance: Implications of Casimir Effects

In his autobiography Casimir barely mentioned the Casimir effect, but remarked that it is "of some theortical significance." We will describe some aspects of Casimir effects that appear to be of particular significance now, more than half a century after Casimir's famous paper

Toronto HCC Risk Index::A validated scoring system to predict 10-year risk of HCC in patients with cirrhosis

Background: Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. Aim: To assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk. Methods: A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system evaluated in an external cohort for validation. Results: Of 2,079 patients with cirrhosis and ≥6 months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease (p&lt;0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low (&lt;120 points) medium (120-240) and high (&gt;240) risk groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with PBC, HBV and HCV cirrhosis (n= 1,144) with similar predictive ability (Harrell’s c-statistic 0.77) in the validation and derivation cohorts. Conclusion: HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis

Cutting Through the Discussion on Caesarean Delivery: Birth Practices as Social Practices

Women are finding appeal in (or, at minimum, a lower level of resistance to) caesarean delivery despite the health risks that it poses, and I investigate how this decision figures into a broader pattern of women\u27s gender socialisation within a culture that is deeply anxious about women\u27s bodies. I review scholarship on caesarean delivery, and use social practice theory to map possible contact points between theories of embodiment, a sociology of gender, and the specific practice of caesarean section. I consider caesarean delivery as a component of a social practice, and adopt a practice framework to analyze women\u27s motivation for selecting (or consenting to) caesarean delivery. I detail the materiality of the hospital, the medicalisation of women\u27s bodies, and women\u27s antagonistic body relationship to reveal some of the less immediately apparent reasons why caesarean delivery has been normalised and rendered invisible as part of the pattern of modern childbirth. Interventions to address the further escalation of caesarean delivery might consider how this decision aligns with other social practices. I conclude that activism addressing the social conditions that make caesarean delivery so attractive may radiate out to other aspects of women\u27s lives where the practices of normative femininity have proven equally restrictive

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial

Aim: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST). Method: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention. The inclusion criteria were age 18–70 years; attending specialist hospitals in England; self-reported constipation for >6 months; refractory to basic treatment. The main exclusions were secondary constipation and previous experience of the trial interventions. The primary outcome was the mean change in Patient Assessment of Constipation Quality of Life score at 6 months on intention to treat. The secondary outcomes were validated disease-specific and psychological questionnaires and cost-effectiveness (based on EQ-5D-5L). Results: In all, 182 patients were randomized 3:3:2 (target 384): HT n = 68; HTBF n = 68; INVEST-guided treatment n = 46. All interventions had similar reductions (improvement) in the primary outcome at 6 months (approximately −0.8 points of a 4-point scale) with no statistically significant difference between HT and HTBF (−0.03 points; 95% CI −0.33 to 0.27; P = 0.85) or INVEST versus no-INVEST (0.22; −0.11 to 0.55; P = 0.19). Secondary outcomes showed a benefit for all interventions with no evidence of greater cost-effectiveness of HTBF or INVEST compared with HT. Conclusion: The results of the study at 6 months were inconclusive. However, with the caveat of under-recruitment and further attrition at 6 months, a simple, cheaper approach to intervention may be as clinically effective and more cost-effective than more complex and invasive approaches

Sedation AND Weaning In Children (SANDWICH): protocol for a cluster randomised stepped wedge trial.

Introduction: Weaning from ventilation is a complex process involving several stages that include recognition of patient readiness to begin the weaning process; steps to reduce ventilation while optimising sedation in order not to induce distress; and removing the endotracheal tube. Delay at any stage can prolong the duration of mechanical ventilation. We developed a multi-component intervention targeted at helping clinicians to safely expedite this process and minimise the harms associated with unnecessary mechanical ventilation. Methods and analysis: This is a 20-month cluster-randomised stepped wedge clinical and cost-effectiveness trial with an internal pilot and a process evaluation. It is being conducted in 18 paediatric intensive care units in the UK to evaluate a protocol-based intervention for reducing the duration of invasive mechanical ventilation. Following an initial eight-week baseline data collection period in all sites, one site will be randomly chosen to transition to the intervention every four weeks and will start an eight-week training period after which it will continue the intervention for the remaining duration of the study. We aim to recruit approximately 10,000 patients. The primary analysis will compare data from before the training (control) with that from after the training (intervention) in each site. Full details of the analyses will be in the statistical analysis plan. Ethics and dissemination: This Protocol was reviewed and approved by NRES Committee East Midlands - Nottingham 1 Research Ethics Committee (reference: 17/EM/0301). All sites started patient recruitment on 5 February 2018 before randomisation in April 2018. Results will be disseminated in 2020. The results will be presented at national and international conferences and published in peer reviewed medical journals

Imposter phenomenon and research experiences among counselor educators

Content analysis was employed to explore research experiences and imposter phenomenon (IP) among 25 counselor educators. Six overarching categories emerged including inconsistent areas of efficacy in the research process, supports in conducting research, barriers in conducting research, experiences of IP across roles, triggers of IP, and factors that quiet IP, with implications for counselor educators