Latent tuberculosis infection screening of adult close contacts in London: a cost-utility analysis

Background: The National Institute for Health and Care Excellence (NICE) guidelines in 2016 recommend tuberculin skin test (TST) at a 5 mm induration size cut-off for latent tuberculosis infection (LTBI) screening of adult close contacts of active tuberculosis (TB) cases. An alternative would be to use an interferon-gamma release assay (IGRA) which has a higher specificity, such as the QuantiFERON-TB Gold in Tube (QFT-GIT) or T-SPOT.TB (T-SPOT). We aimed to evaluate the cost-effectiveness of the screening and treatment of LTBI in adult close contacts with various combinations of these tests in a representative London cohort. Methods: Clinical data of adult close contacts of pulmonary TB cases who were recommended to receive TST and IGRA in a TB clinic in London between 2008 and 2010 were retrospectively reviewed. A Markov decision analytic model, using an NHS perspective and lifetime horizon, was used to compare costs and quality-adjusted life-years (QALYs) associated with 7 screening strategies followed by chemoprophylaxis: TST alone, IGRA (QFT-GIT or T-SPOT) alone, TST positive followed by IGRA, and TST negative followed by IGRA. Future costs and QALYs were discounted at 3.5% per year. Results: 381 asymptomatic close contacts aged 18 to 65 years were included in this study. The mean age was 35.2 years and the majority (75.3%) were BCG vaccinated. In the base-case analysis, QFT-GIT was the most cost-effective strategy with £6876 per QALY gained, compared to TST positive followed by QFT-GIT strategy. QFT-GIT alone averted 1.6 TB cases per 1000 contacts compared to TST positive followed by QFT-GIT. Conclusion: Of the considered testing strategies, the QFT-GIT alone is preferable for LTBI screening in adult close contacts of pulmonary TB cases in London

Identification of antifungal molecules from novel probiotic Lactobacillus bacteria for control of Candida infection

1. Probiotic lactic acid bacteria were identified to have antifungal properties against Candida albicans. 2. The cell-free supernatant of the lactic acid bacteria was successfully fractionated and purified using fast performance liquid chromatography. 3. Eight of the 41 fractions containing the antifungal components exhibited a growth inhibitory effect against C albicans.published_or_final_versio

Iginio Tansini revisited

The origin of the muscolocutaneous latissimus dorsi flap dates back to 1906 when Igino Tansini, an Italian surgeon, described a procedure to reconstruct the mastectomy defect. After a detailed study of Tansini's original description and drawings, new insights about the pedicle of its compound flap have been found, showing that it has the same pedicle of the scapular flap. In the end, Tansini's flap should be more correctly considered as a compound musculocutaneous scapular flap

P109 The impact of tb nice guidance on resource capacity and contact screening outcomes: a retrospective, observational study within a central london tb centre

Introduction and objectives: Recently published NICE guidance has significantly expanded the approach to adult tuberculosis (TB) contact screening by recommending tuberculin skin testing (TST) for pulmonary and laryngeal contacts only, increasing the age threshold for screening and treatment to 65 years and defining a positive TST as induration ≥5 mm, regardless of BCG vaccination status. Interferon Gamma Release Assay (IGRA) is recommended only in situations where more evidence of infection is needed. Our institution has previously adopted an approach comprising a chest radiograph, TST and IGRA. The aim of our study was to evaluate the impact of NICE guidance on screening outcomes and resource capacity by applying the criteria to a well-defined historic cohort of TB contacts. Methods: This was a retrospective, observational study carried out at a central London teaching hospital. The study population comprised 593 consecutive, adult TB contacts screened between 1/1/2008 and 31/12/2010. Data was collected through a retrospective review of TST and IGRA tests. Results: Of the 593 contacts screened, 358 pulmonary contacts had TST and IGRA results. 56% had a TST ≥5 mm, regardless of BCG status, qualifying them for treatment as per the new NICE guidance. Of these, 61% were IGRA negative (discordant) and may therefore include false positive diagnoses, resulting in the potential for over treatment. In those with TST 5–14 mm, discordance rises to 84%. Conversely, 6% of those with TST < 5 mm are IGRA positive representing potentially missed cases. 16% of screened individuals were contacts of extra pulmonary TB. Not screening this group would reduce the demand for outpatient appointments by 151* in our cohort. In contrast, testing contacts > 35 years would require capacity for an additional 165* appointments. Furthermore, there were 162 additional LTBI cases in comparison to previous guidance requiring an additional 648* appointments. 72% of this group were IGRA negative. (*Approximate) Conclusions: Our results show the revised guidance will require increased resource capacity largely due to more patients being classified as having latent TB. In addition to workforce planning to meet these demands, further debate is needed to decide if this new approach truly reduces the incidence of active TB or results in unnecessary treatment

Managing housing needs in post conflict housing reconstruction in Sri Lanka: gaps versus recommendations

Addressing housing needs in post conflict housing reconstruction leads to successful housing reconstruction. As part of a study of investigating how the housing needs can be effectively addressed in post conflict housing reconstruction, this paper identifies the gaps in managing housing needs in post conflict housing reconstruction within the context of Sri Lanka and presents the recommendations to minimise such gaps. Data was collected through un-structured interviews conducted with 37 participants, comprising policy makers, practitioners, academics and beneficiaries who engaged in post conflict housing reconstruction in Sri Lanka. Gaps were mainly found in conflict sensitivity, measures related to physical housing, performance of implementing agencies, policy and practice issues. On the job training, application of ‘do no harm’ principles, enhanced beneficiary participation, enhanced accountability, effective monitoring, enhanced knowledge sharing, adequate drinking water facilities, irrigation development and initiatives for material manufacturing were suggested as recommendations to minimise these gaps. Identification of gaps in managing housing needs in post conflict housing reconstruction and recommendations to minimise them inform policy makers to address the housing needs effectively through incorporating these aspects into the related policies. This in turn enhances the sustainability in housing development after conflicts

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

Uncertainties in climate responses to past land cover change: First results from the LUCID intercomparison study

Seven climate models were used to explore the biogeophysical impacts of human-induced land cover change (LCC) at regional and global scales. The imposed LCC led to statistically significant decreases in the northern hemisphere summer latent heat flux in three models, and increases in three models. Five models simulated statistically significant cooling in summer in near-surface temperature over regions of LCC and one simulated warming. There were few significant changes in precipitation. Our results show no common remote impacts of LCC. The lack of consistency among the seven models was due to: 1) the implementation of LCC despite agreed maps of agricultural land, 2) the representation of crop phenology, 3) the parameterisation of albedo, and 4) the representation of evapotranspiration for different land cover types. This study highlights a dilemma: LCC is regionally significant, but it is not feasible to impose a common LCC across multiple models for the next IPCC assessment

Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies

Expansion microscopy (ExM) enables imaging of preserved specimens with nanoscale precision on diffraction-limited instead of specialized super-resolution microscopes. ExM works by physically separating fluorescent probes after anchoring them to a swellable gel. The first ExM method did not result in the retention of native proteins in the gel and relied on custom-made reagents that are not widely available. Here we describe protein retention ExM (proExM), a variant of ExM in which proteins are anchored to the swellable gel, allowing the use of conventional fluorescently labeled antibodies and streptavidin, and fluorescent proteins. We validated and demonstrated the utility of proExM for multicolor super-resolution (~70 nm) imaging of cells and mammalian tissues on conventional microscopes.United States. National Institutes of Health (1R01GM104948)United States. National Institutes of Health (1DP1NS087724)United States. National Institutes of Health ( NIH 1R01EY023173)United States. National Institutes of Health (1U01MH106011

Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.Massachusetts Institute of Technology. Faculty Discretionary Research FundNational Institutes of Health (U.S.) (Award UL1 RR 025758)Harvard Catalyst (Grant

Evaluation of the HadGEM3-A simulations in view of detection and attribution of human influence on extreme events in Europe

A detailed analysis is carried out to assess the HadGEM3-A global atmospheric model skill in simulating extreme temperatures, precipitation and storm surges in Europe in the view of their attribution to human influence. The analysis is performed based on an ensemble of 15 atmospheric simulations forced with observed Sea Surface Temperature of the 54 year period 1960-2013. These simulations, together with dual simulations without human influence in the forcing, are intended to be used in weather and climate event attribution. The analysis investigates the main processes leading to extreme events, including atmospheric circulation patterns, their links with temperature extremes, land-atmosphere and troposphere-stratosphere interactions. It also compares observed and simulated variability, trends and generalized extreme value theory parameters for temperature and precipitation. One of the most striking findings is the ability of the model to capture North Atlantic atmospheric weather regimes as obtained from a cluster analysis of sea level pressure fields. The model also reproduces the main observed weather patterns responsible for temperature and precipitation extreme events. However, biases are found in many physical processes. Slightly excessive drying may be the cause of an overestimated summer interannual variability and too intense heat waves, especially in central/northern Europe. However, this does not seem to hinder proper simulation of summer temperature trends. Cold extremes appear well simulated, as well as the underlying blocking frequency and stratosphere-troposphere interactions. Extreme precipitation amounts are overestimated and too variable. The atmospheric conditions leading to storm surges were also examined in the Baltics region. There, simulated weather conditions appear not to be leading to strong enough storm surges, but winds were found in very good agreement with reanalyses. The performance in reproducing atmospheric weather patterns indicates that biases mainly originate from local and regional physical processes. This makes local bias adjustment meaningful for climate change attribution