New treatments for hepatitis C virus (HCV): scope for preventing liver disease and HCV transmission in England.

New direct-acting antivirals have the potential to transform the hepatitis C (HCV) treatment landscape, with rates of sustained viral response in excess of 90%. As these new agents are expensive, an important question is whether to focus on minimizing the consequences of severe liver disease, or reducing transmission via 'treatment as prevention'. A back-calculation model was used to estimate the impact of treatment of mild, moderate and compensated cirrhosis on incident cases of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In addition, a dynamic model was used to determine the impact on incidence and prevalence of chronic infection in people who inject drugs (PWID), the main risk group in England. Treating 3500 cirrhotics per year was predicted to reduce ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630 (95% CrI 530-770) in 2020, around half that currently expected, although treating moderate-stage disease will also be needed to sustain this reduction. Treating mild-stage PWID was required to make a substantial impact on transmission: with 2500 treated per year, chronic prevalence/annual incidence in PWID was reduced from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the two goals: treating mild stage had virtually no impact on ESLD/HCC within 15 years, but the long timescale of liver disease means relatively few PWID reach cirrhosis before cessation of injecting. Strategies focussing on treating advanced disease have the potential for dramatic reductions in severe morbidity, but virtually no preventative impact

Ultrasonic Nondestructive Evaluation Using Laser Transducers

A program is described which employs lasers for ultrasonic NDE. A high-power laser is used to generate a brief sound pulse in the test specimen. A second low-power laser then measures the response of the specimen to that sound pulse. The response of the specimen is measured by a “Laser Vibrometer.” This is a novel type of heterodyne interferometer which focuses a Helium-Neon laser beam onto the surface of the specimen and measures its displacement. Displacements as small as 2×10-12 meters on a 0.15 sec averaging time can be detected and also displacements of 1.5×l0-9 meters on a 10-MHz bandwidth. The Laser Vibrometer has a well defined frequency response and does not introduce distortion. The sound generating laser is either a pulsed carbon dioxide TEA laser or a YAG laser. The peak power exceeds 10 M watt. Two mechanisms for generating the sound are discussed. The thermoelastic mechanism relies on the thermal expansion of the surface, causing it to move. The reaction to this causes a pressure pulse in the specimen. Another mechanism allows a small amount of the surface to be ablated and the reaction to this causes a substantial pressure pulse in the specimen. Both laser beams can be scanned over the surface of the specimen by a microprocessor controlled mirror. The microprocessor generates a raster scan of arbitrary size, number of lines, step size and speed. Eventually this technique will allow the inspection of complex specimens without direct contact. This will eliminate the tedium and contact reliability problems associated with conventional piezo-ceramic NDE

Aquatic community response to volcanic eruptions on the Ecuadorian Andean flank: evidence from the palaeoecological record

Aquatic ecosystems in the tropical Andes are under increasing pressure from human modification of the landscape (deforestation and dams) and climatic change (increase of extreme events and 1.5 °C on average temperatures are projected for AD 2100). However, the resilience of these ecosystems to perturbations is poorly understood. Here we use a multi-proxy palaeoecological approach to assess the response of aquatic ecosystems to a major mechanism for natural disturbance, volcanic ash deposition. Specifically, we present data from two Neotropical lakes located on the eastern Andean flank of Ecuador. Laguna Pindo (1°27.132′S–78°04.847′W) is a tectonically formed closed basin surrounded by a dense mid-elevation forest, whereas Laguna Baños (0°19.328′S–78°09.175′W) is a glacially formed lake with an inflow and outflow in high Andean Páramo grasslands. In each lake we examined the dynamics of chironomids and other aquatic and semi-aquatic organisms to explore the effect of thick (> 5 cm) volcanic deposits on the aquatic communities in these two systems with different catchment features. In both lakes past volcanic ash deposition was evident from four large tephras dated to c.850 cal year BP (Pindo), and 4600, 3600 and 1500 cal year BP (Baños). Examination of the chironomid and aquatic assemblages before and after the ash depositions revealed no shift in composition at Pindo, but a major change at Baños occurred after the last event around 1500 cal year BP. Chironomids at Baños changed from an assemblage dominated by Pseudochironomus and Polypedilum nubifer-type to Cricotopus/Paratrichocladius type-II, and such a dominance lasted for approximately 380 years. We suggest that, despite potential changes in the water chemistry, the major effect on the chironomid community resulted from the thickness of the tephra being deposited, which acted to shallow the water body beyond a depth threshold. Changes in the aquatic flora and fauna at the base of the trophic chain can promote cascade effects that may deteriorate the ecosystem, especially when already influenced by human activities, such as deforestation and dams, which is frequent in the high Andes

Alcohol-related brief intervention in patients treated for opiate or cocaine dependence: a randomized controlled study

<p>Abstract</p> <p>Background</p> <p>Despite the importance of heavy drinking and alcohol dependence among patients with opiate and cocaine dependence, few studies have evaluated specific interventions within this group. The aim of the present study was to evaluate the impact of screening with the Alcohol Use Disorders Identification Test (AUDIT) and of brief intervention (BI) on alcohol use in a sample of patients treated for opioid or cocaine dependence in a specialized outpatient clinic.</p> <p>Methods</p> <p>Adult outpatients treated for opioid or cocaine dependence in Switzerland were screened for excessive alcohol drinking and dependence with the AUDIT. Patients with AUDIT scores that indicated excessive drinking or dependence were randomized into two groups--treatment as usual or treatment as usual together with BI--and assessed at 3 months and 9 months.</p> <p>Results</p> <p>Findings revealed a high rate (44%) of problematic alcohol use (excessive drinking and dependence) among patients with opiate and cocaine dependence. The number of drinks per week decreased significantly between T0 (inclusion) and T3 (month 3). A decrease in average AUDIT scores was observed between T0 and T3 and between T0 and T9 (month 9). No statistically significant difference between treatment groups was observed.</p> <p>Conclusions</p> <p>In a substance abuse specialized setting, screening for alcohol use with the AUDIT, followed by feedback on the score, and use of alcohol BI are both possibly useful strategies to induce changes in problematic alcohol use. Definitive conclusions cannot, however, be drawn from the study because of limitations such as lack of a naturalistic group. An important result of the study is the excellent internal consistency of AUDIT in a population treated for opiate or cocaine dependence.</p

Review: Allelochemicals as multi-kingdom plant defence compounds: towards an integrated approach

© 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. The capability of synthetic pesticides to manage weeds, insect pests and pathogens in crops has diminished due to evolved resistance. Sustainable management is thus becoming more challenging. Novel solutions are needed and, given the ubiquity of biologically active secondary metabolites in nature, such compounds require further exploration as leads for novel crop protection chemistry. Despite improving understanding of allelochemicals, particularly in terms of their potential for use in weed control, their interactions with multiple biotic kingdoms have to date largely been examined in individual compounds and not as a recurrent phenomenon. Here, multi-kingdom effects in allelochemicals are introduced by defining effects on various organisms, before exploring current understanding of the inducibility and possible ecological roles of these compounds with regard to the evolutionary arms race and dose–response relationships. Allelochemicals with functional benefits in multiple aspects of plant defence are described. Gathering these isolated areas of science under the unified umbrella of multi-kingdom allelopathy encourages the development of naturally-derived chemistries conferring defence to multiple discrete biotic stresses simultaneously, maximizing benefits in weed, insect and pathogen control, while potentially circumventing resistance. © 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry

N-terminally cleaved Bcl-x(L) mediates ischemia-induced neuronal death

Transient global ischemia in rats induces delayed death of hippocampal CA1 neurons. Early events include caspase activation, cleavage of anti-death Bcl-2 family proteins and large mitochondrial channel activity. However, whether these events have a causal role in ischemia-induced neuronal death is unclear. We found that the Bcl-2 and Bcl-xL inhibitor ABT-737, which enhances death of tumor cells, protected rats against neuronal death in a clinically relevant model of brain ischemia. Bcl-xL is prominently expressed in adult neurons and can be cleaved by caspases to generate a pro-death fragment, ΔN-Bcl-xL. We found that ABT-737 administered before or after ischemia inhibited ΔN-Bcl-xL–induced mitochondrial channel activity and neuronal death. To establish a causal role for ΔN-Bcl-xL, we generated knock-in mice expressing a caspase-resistant form of Bcl-xL. The knock-in mice exhibited markedly reduced mitochondrial channel activity and reduced vulnerability to ischemia-induced neuronal death. These findings suggest that truncated Bcl-xL could be a potentially important therapeutic target in ischemic brain injury

Critical Role of Macrophages and Their Activation via MyD88-NFκB Signaling in Lung Innate Immunity to Mycoplasma pneumoniae

Mycoplasma pneumoniae (Mp), a common cause of pneumonia, is associated with asthma; however, the mechanisms underlying this association remain unclear. We investigated the cellular immune response to Mp in mice. Intranasal inoculation with Mp elicited infiltration of the lungs with neutrophils, monocytes and macrophages. Systemic depletion of macrophages, but not neutrophils, resulted in impaired clearance of Mp from the lungs. Accumulation and activation of macrophages were decreased in the lungs of MyD88−/− mice and clearance of Mp was impaired, indicating that MyD88 is a key signaling protein in the anti-Mp response. MyD88-dependent signaling was also required for the Mp-induced activation of NFκB, which was essential for macrophages to eliminate the microbe in vitro. Thus, MyD88-NFκB signaling in macrophages is essential for clearance of Mp from the lungs

Primary care provider perceptions of intake transition records and shared care with outpatient cardiac rehabilitation programs

Abstract Background While it is recommended that records are kept between primary care providers (PCPs) and specialists during patient transitions from hospital to community care, this communication is not currently standardized. We aimed to assess the transmission of cardiac rehabilitation (CR) program intake transition records to PCPs and to explore PCPs' needs in communication with CR programs and for intake transition record content. Method 144 PCPs of consenting enrollees from 8 regional and urban Ontario CR programs participated in this cross-sectional study. Intake transition records were tracked from the CR program to the PCP's office. Sixty-six PCPs participated in structured telephone interviews. Results Sixty-eight (47.6%) PCPs received a CR intake transition record. Fifty-eight (87.9%) PCPs desired intake transition records, with most wanting it transmitted via fax (n = 52, 78.8%). On a 5-point Likert scale, PCPs strongly agreed that the CR transition record met their needs for providing patient care (4.32 ± 0.61), with 48 (76.2%) reporting that it improved their management of patients' cardiac risk. PCPs rated the following elements as most important to include in an intake transition record: clinical status (4.67 ± 0.64), exercise test results (4.61 ± 0.52), and the proposed patient care plan (4.59 ± 0.71). Conclusions Less than half of intake transition records are reaching PCPs, revealing a large gap in continuity of patient care. PCP responses should be used to develop an evidence-based intake transition record, and procedures should be implemented to ensure high-quality transitional care