Drug-induced liver injury

Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paractamol overdose, nearly all DILI encountered in the clinical setting is idiosyncratic in nature, since affected individuals represent only a small proportion of those treated with such drugs. In many cases the mechanism for idiosyncrasy is immune mediation and is often identified by genetic risk determined by HLA variants. In the absence of diagnostic tests and/or biomarkers, the diagnosis of DILI requires a high index of suspicion after diligently excluding other causes of abnormal liver tests. Antibiotics are the class of drugs most frequently associated with idiosyncratic DILI, though recent studies indicate that herbal and dietary supplements are an increasingly recognised cause. It is imperative that upon development of DILI the culprit drug be discontinued especially in the presence of elevated transaminases (AST/ALT ≥5ULN) and/or jaundice. Risk factors for the development ALF include hepatocellular DILI and female gender, the treatment being supportive with some benefit of N-acetylcysteine in early stages. In view of the poor transplant-free survival in idiosyncratic DILI, early consideration for liver transplant is mandatory

The Impact of Environmental Factors on Emergency Medicine Resident Career Choice

Objective: To evaluate the impact of environmental factors on emergency medicine (EM) resident career choice. Methods: Program directors of all U.S. EM residencies were surveyed in November 1997. A 22-item questionnaire assessed resources allocated to research, fellowship availability, academic productivity of faculty and residents, and career choices of residency graduates. Results: The response rate was 83%. The program director (mean ± SD) estimates of resident career choice were as follows: 27.8 ± 19.1% pursued academic positions with emphasis on teaching, 5.4 ± 9.8% pursued academic positions with emphasis on research, and 66.8 ± 23.1%, pursued private practice positions. In addition, 5.70 ± 6.13% of the residency graduates were estimated to seek felloship training. Univariate analyses demonstrated that increasing departmental funding for research, having substantial resource availability (defined as having at least two of the following: dedicated laboratory space; support for a laboratory research technician/assistant, a clinical research nurse or study coordinator, a statistician, or an assistant with a PhD degree), a greater number of peer-reviewed publications by residents (r = 0.22; p = 0.08), and a greater number of peer-reviewed publications by faculty (r = 0.26; p = 0.04) positively correlated with the percentage of graduates who pursue academic research careers. Using multiple regression, however, increasing intramural funding and the presence of substantial resource availability were the only variables predictive of resident pursuit of an academic research career. Conclusion: Modification of the EM training environment may influence the career choices of graduates. Specifically, greater commitment of departmental funds and support of resources for research may enhance the likelihood of a trainee's choosing an academic research career.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72940/1/j.1553-2712.1999.tb00387.x.pd

Uncoupling growth from phosphorus uptake in Lemna: Implications for use of duckweed in wastewater remediation and P recovery in temperate climates

Phosphorus (P) is an essential nutrient for crop growth and the second most limiting after N. Current supplies rely on P‐rich rocks that are unevenly distributed globally and exploited unsustainably, leading to concerns about future availability and therefore food security. Duckweeds (Lemnaceae) are aquatic macrophytes used in wastewater remediation with the potential for nutrient recycling as feed or fertilizer. The use of duckweeds in this way is confined to tropical regions as it has previously been assumed that growth in the colder seasons of the temperate regions would be insufficient. In this study, the combined effects of cool temperatures and short photoperiods on growth and P uptake and accumulation in Lemna were investigated under controlled laboratory conditions. Growth and P accumulation in Lemna can be uncoupled, with significant P removal from the medium and accumulation within the plants occurring even at 8°C and 6‐hr photoperiods. Direct measurement of radiolabeled phosphate uptake confirmed that while transport is strongly temperature dependent, uptake can still be measured at 5°C. Prior phosphate starvation of the duckweed and use of nitrate as the nitrogen (N) source also greatly increased the rate of P removal and in‐cell accumulation. These results form the basis for further examination of the feasibility of duckweed‐based systems for wastewater treatment and P recapture in temperate climates, particularly in small, rural treatment works

Gamow-Teller strength distributions for nuclei in pre-supernova stellar cores

Electron-capture and $\beta$-decay of nuclei in the core of massive stars play an important role in the stages leading to a type II supernova explosion. Nuclei in the f-p shell are particularly important for these reactions in the post Silicon-burning stage of a presupernova star. In this paper, we characterise the energy distribution of the Gamow-Teller Giant Resonance (GTGR) for mid-fp-shell nuclei in terms of a few shape parameters, using data obtained from high energy, forward scattering (p,n) and (n,p) reactions. The energy of the GTGR centroid $E_{GT}$ is further generalised as function of nuclear properties like mass number, isospin and other shell model properties of the nucleus. Since a large fraction of the GT strength lies in the GTGR region, and the GTGR is accessible for weak transitions taking place at energies relevant to the cores of presupernova and collapsing stars, our results are relevant to the study of important $e^-$-capture and $\beta$-decay rates of arbitrary, neutron-rich, f-p shell nuclei in stellar cores. Using the observed GTGR and Isobaric Analog States (IAS) energy systematics we compare the coupling coefficients in the Bohr-Mottelson two particle interaction Hamiltonian for different regions of the Isotope Table.Comment: Revtex, 28 pages +7 figures (PostScript Figures, uuencoded, filename: Sutfigs.uu). If you have difficulty printing the figures, please contact [email protected]. Accepted for publication in Phys. Rev. C, Nov 01, 199

Time-resolved spatial distributions of individual components of electroactive films during potentiodynamic electrodeposition

Of the attributes that determine the performance of electroactive film-based devices, the least well quantified and understood is the spatial distribution of the component species. This is critical since it dictates the transport rates of all the mobile species (electrons, counterions, solvent, analyte, and reactant) and the film mechanical properties (as exploited in actuator devices). One of the few techniques able to provide individual species population profiles in situ is specular neutron reflectivity (NR). Historically, this information is obtained at the cost of poor time resolution (hours). Here we show how NR measurements with event mode data acquisition enable both spatial and temporal resolution; the latter can be selected postexperiment and varied during the transient. We profile individual species at “buried” interfaces under dynamic electrochemical conditions during polypyrrole electrodeposition and Cu deposition/dissolution. In the case of polypyrrole, the film is homogeneous throughout growth; there is no evidence of dendrite formation followed by solvent (water) displacement. Correlation of NR-derived film thickness and coulometric assay allows calculation of the solvent volume fraction, ϕS = 0.48. In the case of Cu in a deep eutectic solvent, the complexing nature of the medium results in time-dependent metal speciation: mechanistically, dissolution does not simply follow the deposition pathway in reverse

Rates of Tuberculosis Infection in Healthcare Workers Providing Services to HIV-Infected Populations

Objective: To assess the prevalence of tuberculosis (TB) or a positive skin test in healthcare workers (HCWs) providing services to human immunodeficiency virus (HIV)-infected individuals and to determine prospectively the incidence of new infections in this population. Design: This prospective cohort study enrolled 1,014 HCWs working with HIV-infected populations from 10 metropolitan areas. Purified protein derivative (PPD) tuberculin skin tests were placed at baseline and every 6 months afterwards on those without a history of TB or a positive PPD. Demographic, occupational, and TB exposure data also were collected. Setting: Outpatient clinics, hospitals, private practice offices, and drug treatment programs providing HIV-related healthcare and research programs. Participants: A voluntary sample of staff and volunteers from 16 Community Programs for Clinical Research on AIDS units. Results: Factors related to prior TB or a positive skin test at baseline included being foreign-born, increased length of time in health care, living in New York City, or previous bacille Calmette-Guerín vaccination. The rate of PPD conversion was 1.8 per 100 person years of follow-up. No independent relation was found between the amount or type of contact with HIV-infected populations and the risk of TB infection. Conclusion: These data provide some reassurance that caring for HIV-infected patients is not related to an increased rate ofTB infection among HCWs in these settings

Who, where, when: the demographic and geographic distribution of bicycle crashes in West Yorkshire

Factors associated with cycle safety, including international differences in injury and mortality rates, protective equipment and bicycle training, have been subject to increasing academic interest. Environmental variables associated with cycle safety have also been scrutinised, but few studies have focussed on geographical factors at the local level. This paper addresses this research gap by analysing a geo-referenced dataset of road traffic incidents, taken from the UK's STATS19 dataset (2005 - 2012). We investigate incidents involving cyclists within West Yorkshire. This is an interesting case study area as it has an historically low cycling rate but very ambitions cycling plans following investment from the Department for Transport. West Yorkshire is found to be an unusually risky area for cyclists, with an estimated 53 deaths and 1372 serious injuries per billion kilometres cycled, based on census commuting statistics. This is roughly double the national average. This riskiness varies spatially and temporally, broadly in line with expectations from the previous literature. An unexpected result was that cycling seems to be disproportionately risky for young people in West Yorkshire compared with young people nationally. The case study raises the issue of potential negative health impacts of promoting cycling amongst vulnerable groups in dangerous areas. We conclude by highlighting opportunities for increasing cycling uptake via measures designed primarily to improve safety. The analysis underlying this research is reproducible, based on code stored at https://github.com/Robinlovelace/bikeR

Real-time in situ dynamic sub-surface imaging of multi-component electrodeposited films using event mode neutron reflectivity

Exquisite control of the electrodeposition of metal films and coatings is critical to a number of high technology and manufacturing industries, delivering functionality as diverse as anti- corrosion and anti-wear coatings, electronic device interconnects and energy storage. The frequent involvement of more than one metal motivates the capability to control, maintain and monitor spatial disposition of the component metals, whether as multilayers, alloys or composites. Here we investigate the deposition, evolution and dissolution of single and two- component metal layers involving Ag, Cu, and Sn on Au substrates immersed in the deep eutectic solvent (DES) Ethaline. During galvanostatically controlled stripping of the metals from two-component systems the potential signature in simultaneous thickness electrochemical potential (STEP) measurements provides identification of the dissolving metal; coulometric assay of deposition efficiency is an additional outcome. When combined with quartz crystal microbalance (QCM) frequency responses, the mass change:charge ratio provides oxidation state data; this is significant for Cu in the high chloride environment provided by Ethaline. The spatial distribution (solvent penetration and external roughness) of multiple components in bilayer systems is provided by specular neutron reflectivity (NR). Significantly, the use of recently established event mode capability shortens the observational timescale of the NR measurements by an order of magnitude, permitting dynamic in situ observations on practically useful timescales. Ag,Cu bilayers of both spatial configurations give identical STEP signatures indicating that, despite the extremely low layer porosity, thermodynamic constraints (rather than spatial accessibility) dictate reactivity; thus, surprisingly, Cu dissolves first in both instances. Sn penetrates the Au electrode on the timescale of deposition; this can be prevented by interposing a layer of either Ag or Cu

The effects of corporate and country sustainability characteristics on the cost of debt: an international investigation

We investigate the relationship between corporate and country sustainability on the cost of bank loans. We look into 470 loan agreements signed between 2005 and 2012 with borrowers based in 28 different countries across the world and operating in all major industries. Our principal findings reveal that country sustainability, relating to both social and environmental frameworks, has a statistically and economically impactful effect on direct financing of economic activity. An increase of one unit in a country's sustainability score is associated with an average decrease in the cost of debt by 64 basis points. Our international analysis shows that the environmental dimension of a country's institutional framework is approximately twice as impactful as the social dimension, when it comes to determining the cost of corporate loans. On the other hand, we find no conclusive evidence that firm-level sustainability influences the interest rates charged to borrowing firms by banks. Our main findings survive a battery of robustness tests and additional analyses concerning subsamples, alternative sustainability metrics and the effects of financial crisis

HPV-Related Anal Cancer Is Associated With Changes in the Anorectal Microbiome During Cancer Development

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. METHODS: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer. RESULTS: 60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p CONCLUSION: Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorecta