A systematic review of outcome measures used in clinical trials of treatment interventions following traumatic dental injuries

Background: Traumatic dental injuries (TDI) are common, andappropriate treatment will maximize the chances of maintaining teeth infunction while safeguarding their longevity and aesthetics. Subjectively, itappears that outcome measures used in studies investigating TDI arenumerous and diverse. Objectives: To undertake a systematic review ofthe outcomes used in clinical trials of treatment interventions followingTDI. Data sources: The MEDLINE, Cochrane Central Register of Con-trolled Trials, Cochrane Database of Systematic Reviews and EMBASEdatabases were searched up to June 2014. Reference lists of eligible studieswere cross-checked to identify additional studies and strategies to identifygrey literature and ongoing trials were employed. Study selection: Twoauthors independently assessed studies for inclusion and undertook dataextraction. The study designs included were as follows: systematic reviewswith/without meta-analyses, randomized and pseudo-randomized con-trolled trials and controlled clinical trials. There were no language restric-tions. Results: Ten studies confined to two types of TDI were included:avulsion (5) and non-vital immature permanent incisor teeth (5). The out-comes reported predominantly concentrated on injury activity and thephysical consequence of injury. There was little consistency between studiesfor the length of follow up, the time points at which outcomes were evalu-ated or the methods used to measure them. Conclusions: There is signifi-cant heterogeneity in outcomes reported for TDI in the literature. Thesefindings preclude meaningful meta-analysis between studies. Future clinicalstudies need to consider collecting a more consistent and wider range ofoutcomes, which should include one or more from each of the followingdomains: health resources utilisation, adverse effects and quality of life andfamily outcome. There is a clear need for the development of a Core Out-come Set for TDI using robust and established methodology, thus optimiz-ing the value of future research

The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is a complex disease trait where genetic variations and environment interact to determine disease progression. The association of PNPLA3 with advanced disease has been consistently demonstrated but many other modifier genes remain unidentified. In NAFLD, increased fatty acid oxidation produces high levels of reactive oxygen species. Manganese-dependent superoxide dismutase (MnSOD), encoded by the SOD2 gene, plays an important role in protecting cells from oxidative stress. A common non-synonymous polymorphism in SOD2 (C47T; rs4880) is associated with decreased MnSOD mitochondrial targeting and activity making it a good candidate modifier of NAFLD severity. METHODS: The relevance of the SOD2 C47T polymorphism to fibrotic NAFLD was assessed by two complementary approaches: we sought preferential transmission of alleles from parents to affected children in 71 family trios and adopted a case-control approach to compare genotype frequencies in a cohort of 502 European NAFLD patients. RESULTS: In the family study, 55 families were informative. The T allele was transmitted on 47/76 (62%) possible occasions whereas the C allele was transmitted on only 29/76 (38%) occasions, p=0.038. In the case control study, the presence of advanced fibrosis (stage>1) increased with the number of T alleles, p=0.008 for trend. Multivariate analysis showed susceptibility to advanced fibrotic disease was determined by SOD2 genotype (OR 1.56 (95% CI 1.09-2.25), p=0.014), PNPLA3 genotype (p=0.041), type 2 diabetes mellitus (p=0.009) and histological severity of NASH (p=2.0×10(-16)). CONCLUSIONS: Carriage of the SOD2 C47T polymorphism is associated with more advanced fibrosis in NASH

Extraordinary human energy consumption and resultant geological impacts beginning around 1950CE initiated the proposed Anthropocene Epoch

Growth in fundamental drivers—energy use, economic productivity and population—can provide quantitative indications of the proposed boundary between the Holocene Epoch and the Anthropocene. Human energy expenditure in the Anthropocene, ~22 zetajoules (ZJ),exceeds that across the prior 11,700 years of the Holocene (~14.6 ZJ), largely through combustion of fossil fuels. The global warming effect during the Anthropocene is more thanan order of magnitude greater still. Global human population, their productivity and energy consumption, and most changes impacting the global environment, are highly correlated. This extraordinary outburst of consumption and productivity demonstrates how the Earth System has departed from its Holocene state since ~1950 CE, forcing abrupt physical, chemical and biological changes to the Earth’s stratigraphic record that can be used to justify the proposal for naming a new epoch—the Anthropocene

A regulation-based classification system for marine protected areas: A response to Dudley et al. [9]

Dudley et al. [9] commented on our paper [11], arguing that the current IUCN objective-based categorization of protected areas, which is also used in marine protected areas (MPAs), should not be abandoned and replaced by the new regulation-based classification system [11]. Here we clarify that we do not advocate replacing the current IUCN categories, but highlight the benefits of using both the objective-based IUCN categories and the new regulation-based classification when applied to MPAs. With an increasing number of MPA types being implemented, most of them multiple-use areas zoned for various purposes, assessing ecological and socio-economic benefits is key for advancing conservation targets and policy objectives. Although the IUCN categories can be used both in terrestrial and marine systems, they were not designed to follow a gradient of impacts and there is often a mismatch between stated objectives and implemented regulations. The new regulation-based classification system addresses these problems by linking impacts of activities in marine systems with MPA and zone classes in a simple and globally applicable way. Applying both the IUCN categories and the regulation based classes will increase transparency when assessing marine conservation goals.ERA-Net BiodivERsA project "BUFFER Partially protected areas as buffers to increase the linked social ecological resilience"; national funders ANR (France); FCT (Portugal); FOR-MAS (Sweden); SEPA (Sweden); RCN (Norway); project BUFFER; Fernand Braudel IFER fellowship (Fondation Maison des Sciences de l'Homme); Fundacao para a Ciencia e a Tecnologia (FCT) [UID/MAR/04292/2013

The association between mentoring and training outcomes in junior doctors in medicine: an observational study.

OBJECTIVE: To determine quantitatively if a positive association exists between the mentoring of junior doctors and better training outcomes in postgraduate medical training within the UK. DESIGN: Observational study. PARTICIPANTS: 117 trainees from the East of England Deanery (non-mentored group) and the recently established Royal College of Physicians (RCP) Mentoring scheme (mentored group) who were core medical trainees (CMTs) between 2015 and 2017 completed an online survey. Trainees who received mentoring at the start of higher specialty training, incomplete responses and trainees who were a part of both the East of England deanery and RCP Mentoring scheme were excluded leaving 85 trainees in the non-mentored arm and 25 trainees in the mentored arm. Responses from a total of 110 trainees were analysed. MAIN OUTCOME MEASURES: Pass rates of the various components of the Membership of the Royal College of Physicians (MRCP) (UK) examination (MRCP Part 1, MRCP Part 2 Written and MRCP Part 2 PACES), pass rates at the Annual Review of Competency Progression (ARCP), trainee involvement in significant events, clinical incidents or complaints and trainee feedback on career progression and confidence. RESULTS: Mentored trainees reported higher pass rates of the MRCP Part 1 exam versus non-mentored trainees (84.0% vs 42.4%, p<0.01). Mentored international medical graduates (IMGs) reported higher pass rates than non-mentored IMGs in the MRCP Part 2 Written exam (71.4% vs 24.0%, p<0.05). ARCP pass rates in mentored trainees were observed to be higher than non-mentored trainees (95.8% vs 69.9%, p<0.05). Rates of involvement in significant events, clinical incidents and complaints in both groups did not show any statistical difference. Mentored trainees reported higher confidence and career progression. CONCLUSIONS: A positive association is observed between the mentoring of CMTs and better training outcomes. Further studies are needed to investigate the causative effects of mentoring in postgraduate medical training within the UK

A rapid analysis platform for investigating the cellular locations of bacteria using two-photon fluorescence lifetime imaging microscopy

Facultative intracellular pathogens are able to live inside and outside host cells. It is highly desirable to differentiate their cellular locations for the purposes of fundamental research and clinical applications. In this work, we developed a novel analysis platform that allows users to choose two analysis models: amplitude weighted lifetime (τA) and intensity weighted lifetime (τI) for fluorescence lifetime imaging microscopy (FLIM). We applied these two models to analyse FLIM images of mouse Raw macrophage cells that were infected with bacteria Shigella Sonnei, adherent and invasive E. coli (AIEC) and Lactobacillus. The results show that the fluorescence lifetimes of bacteria depend on their cellular locations. The τA model is superior in visually differentiating bacteria that are in extra- and intra-cellular and membrane-bounded locations, whereas the τI model show excellent precision. Both models show speedy performances that analysis can be performed within 0.3 second. We also compared the proposed models with a widely used commercial software tool (τC, SPC Image, Becker & Hickl GmbH), showing similar τI and τC results. The platform also allows users to perform phasor analysis with great flexibility to pinpoint the regions of interest from lifetime images as well as phasor plots. This platform holds the disruptive potential of replacing z-stack imaging for identifying intracellular bacteria

Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis

Over the past two decades a number of studies have demonstrated activity of the retroviral enzyme reverse transcriptase in the serum of patients with sporadic amyotrophic lateral sclerosis (ALS). Known human exogenous retroviruses such as HIV-1 have been eliminated as possible sources of this activity and investigators have therefore considered the possibility that human endogenous retroviruses (HERVs) might be involved. HERV-K (HML-2) is the most recent retroviral candidate to be proposed following the observation of elevated HERV-K expression in cortical and spinal neurons of ALS patients and the demonstration of HERV-K envelope protein neurotoxicity in vitro and in transgenic mice. This retroviral hypothesis is an attractive one, not least because it raises the possibility that ALS might become treatable using antiretroviral drugs. In the present study we have attempted independent confirmation of the observation that HERV-K RNA levels are elevated in ALS brain. Total RNA was extracted from the postmortem premotor cortex of 34 patients with ALS and 23 controls. Quantitative real-time reverse transcription PCR (RT-qPCR) was performed according to the MIQE guidelines using HERV-K gag, pol and env primer sets. Data was analysed by the 2-∆∆Ct method with normalisation against two reference genes, GAPDH and XPNPEP1. Geometric mean HERV-K RNA expression levels in the premotor cortex of ALS patients were not found to be different from the expression levels in non-ALS controls. Our findings do not confirm the recently reported association between elevated cortical HERV-K RNA levels and ALS, and thus raise doubts about the role of this endogenous retrovirus in ALS pathogenesis. The results of this study may have implications for ongoing clinical trials aiming to suppress HERV-K activity with antiretroviral drugs