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Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
This presentation will enable the learner to:
1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.
Micronutrient supplementation is recommended in Ebola Virus Disease (EVD). However, there is limited data on its therapeutic impacts. This study evaluated the association between vitamin A supplementation and mortality outcomes in EVD patients.
This retrospective cohort study accrued patients with EVD admitted to five International Medical Corps run Ebola Treatment Units (ETU) in two countries from 2014-2015. Protocolized treatments with antimicrobials and micronutrients were used at all ETUs. However, due to resource limitations and care variations, only a subset of patients received vitamin A. Standardized data on demographics, clinical characteristics, malaria status, and Ebola virus RT-PCR cycle threshold (CT) values were collected. The outcome of interest was mortality compared between cases treated with 200,000 International Units of vitamin A on care days one and two and those not. Propensity scores (PS) based on the first 48-hours of care were derived using the covariates of age, duration of ETU function, malaria status, CT values, symptoms of confusion, hemorrhage, diarrhea, dysphagia, and dyspnea. Treated and non-treated cases were matched 1:1 based on nearest neighbors with replacement. Covariate balance met predefined thresholds. Mortality proportions between cases treated and untreated with vitamin A were compared using generalized estimating equations to calculate relative risks (RR) with associated 95% confidence intervals (CI).
There were 424 cases analyzed, with 330 (77.8%) being vitamin A-treated cases. The mean age was 30.5 years and 57.0% were female. The most common symptoms were diarrhea (86%), anorexia (81%), and vomiting (77%). Mortality proportions among cases untreated and treated with vitamin A were 71.9% and 55.0%, respectively. In a propensity-matched analysis, mortality was significantly lower among cases receiving vitamin A (RR = 0.77 95%; CI:0.59-0.99; p = 0.041).
Early vitamin A supplementation was associated with reduced mortality in EVD patients and should be provided routinely during future epidemics.
The effects of growing pinto peanut mixed with elephant grass-based pastures are still little known. The aim of the current research was to evaluate the performance of herbage yield, nutritive value of forage and animal responses to levels of pinto peanut forage mass mixed with elephant grass in low-input systems. Three grazing systems were evaluated: (i) elephant grass-based (control); (ii) pinto peanut, low-density forage yield (63 g/kg of dry matter – DM) + elephant grass; and (iii) pinto peanut, high-density dry matter forage yield (206 g/kg DM) + elephant grass. The experimental design was completely randomized with the three treatments (grazing systems) and three replicates (paddocks) in split-plot grazing cycles. Forage samples were collected to evaluate the pasture and animal responses. Leaf blades of elephant grass and the other companion grasses of pinto peanut were collected to analyse the crude protein, in vitro digestible organic matter and total digestible nutrients. The pinto peanut, high-density dry matter forage yield + elephant grass treatment was found to give the best results in terms of herbage yield, forage intake and stocking rate, as well as having higher crude protein contents for both elephant grass and the other grasses, followed by pinto peanut with low-density forage yield + elephant grass and finally elephant grass alone. Better results were found with the grass–legume system for pasture and animal responses.
OBJECTIVES/SPECIFIC AIMS: The overall goal of this project is to enhance the use of GCRA in Latina breast cancer survivors at high risk of hereditary breast and ovarian cancer to reduce disparities in GCRA uptake. The aims of the study are to (1) develop a cultural adaptation of an evidence-based TGC intervention that consists of phone genetic counseling and a booklet, (2) evaluate the impact of TGC Versus Usual Care, and (3) explore the communication patterns in TGC and genetic counseling sessions with an interpreter. METHODS/STUDY POPULATION: We are conducting a 2-phase, mixed methods study. In Phase I we will develop a cultural adaption of an evidence-based intervention (TGC) for high-risk Latina breast cancer survivors using the Learner Verification and Revision Framework (n=15). In Phase II we will use a cluster randomized design with four community sites randomized to Spanish TGC (n=2 sites) or usual care (n=2 sites) (n=60; 15 per site). The primary outcome is genetic counseling uptake. Among women who receive genetic counseling either through TGC (n~30) or with an interpreter (n~15), we will assess counseling quality by reviewing 20 randomly selected audiotaped sessions (10 TGC; 10 interpreters). We will evaluate women’s HBOC knowledge and satisfaction with counseling. Communication processes and outcomes will be assessed using gold standard RIAS quantitative coding system and qualitative discourse analysis. RESULTS/ANTICIPATED RESULTS: We elicited input from transdisciplinary team members to develop an initial adaptation of a TGC print booklet and intervention protocol for use with high-risk Latina breast cancer survivors with limited English proficiency. The booklet contains low-literacy information about HBOC, risk factors, pros and cons of testing, and management strategies. Based on these materials and prior work, we anticipate TGC will consist of one 1 hour or less TGC session by phone. Participants interested in pursuing testing will receive a saliva kit and will participate in a second TGC session (30 min) to discuss test results and management options. DISCUSSION/SIGNIFICANCE OF IMPACT: Given access barriers and the shortage of Spanish-speaking genetic counselors, adapting and translating TGC intervention is a promising strategy that could reduce disparities by broadening the reach and accessibility to genetic counseling while enhancing the quality of the service for Latinas with limited English proficiency.
Monolithic integrated thin film tandem solar cells consisting of a high bandgap perovskite top cell and a low bandgap thin film bottom cell are expected to reach higher power conversion efficiencies (PCEs) with lower manufacturing cost and environmental impacts than the market-dominant crystalline silicon photovoltaics. There have been several demonstrations of 4-terminal and 2-terminal perovskite tandem devices with CuInGaSe2 (CIGS) or CuInSe2 (CIS) and, similar to the other tandem structures, the optimization of this device relies on optimal choice for the perovskite bandgap and thickness. Therefore, further advancement will be enabled by tuning the perovskite absorber to maximize the photocurrent limited by the current match condition. Here, we systematically study the optical absorption and transmission of perovskite thin films with varying absorber band gap. Based on these results, we model the photocurrent generations in both perovskite and CIS subcells and estimate the performances of projected tandem devices by considering the ideally functioning perovskite and CIS device. Our results show that for perovskite layers with 500 nm thickness the optimal bandgap is around 1.6 eV. With these configurations, PCEs above 20% could be achieved by monolithically integrated perovskite/CIS tandem solar cells. Also by modelling the absorption at every layer we calculate the quantum efficiency at each subcell in addition to tracking optical losses.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Methods of obtaining large grain size and high crystallinity in absorber materials play an important role in fabrication of high-performance methylammonium lead iodide (MAPbI3) perovskite solar cells. Here we study the effect of adding small concentrations of Cd2+, Zn2+, and Fe2+salts to the perovskite precursor solution used in the single-step solution fabrication process. Enhanced grain size and crystallinity in MAPbI3 films were obtained by using 0.1% of Cd2+ or Zn2+in the precursor solution. Consequently, solar cells constructed with Cd- and Zn-doped perovskite films show a significant improvement in device performance. These results suggest that the process may be an effective and facile method to fabricate high-efficiency perovskite photovoltaic devices.
Mesoporous silicas were synthesized via a surfactant-templated sol-gel route using castor oil as the templating agent under acidic medium. The resulting silicas were subsequently amine functionalized with 3-aminopropyltriethoxysilane (NH2-MTS), [3-(2-aminoethylamino)-propyl]trimethoxysilane (NN-MTS), and [3-(diethylamino)propyl]trimethoxysilane(DN-MTS) to introduce surface basicity. Surface physicochemical properties were characterized by field emission gun scanning electron microscopy (FEGSEM), nitrogen porosimetry, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and diffuse reflectance infrared fourier transform spectroscopy (DRIFTS). As-synthesised materials exhibit type IV adsorption-desorption isotherms characteristic of mesoporous structures. Clusters of spherical shaped materials were observed by FEGSEM, suggesting growth of silica occurs within colloidal dispersions. High-resolution N 1s XP spectra and DRIFT spectra confirmed the presence of amine groups in the organo-amine functionalised mesoporous silicas. The amine functionalised mesoporous silicas were active for the transesterification of tributyrin with methanol, with conversion found to increase from NH2-MTS< NN-MTS< DN-MTS.
The clinical and pathologic characterisation of two fatal cases of tick-borne rickettsiosis in rural (El Valle) and urban (City of Panama) Panama are described. Clinical and autopsy findings were non-specific, but the molecular analysis was used to identify Rickettsia rickettsii in both cases. No ticks were collected in El Valle, while in the urban case, R. rickettsii was detected in Rhipicephalus sanguineus s.l., representing the first molecular finding in this tick in Panama and Central America.
22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of neurodevelopmental disorder, however, the links between developmental coordination disorder (DCD), intellectual function and psychiatric disorder remain unexplored.
To establish the prevalence of indicative DCD in children with 22q11.2DS and examine associations with IQ, neurocognition and psychopathology.
Neurocognitive assessments and psychiatric interviews of 70 children with 22q11.2DS (mean age 11.2, s.d. = 2.2) and 32 control siblings (mean age 11.5, s.d. = 2.1) were carried out in their homes. Nine children with 22q11.2DS and indicative DCD were subsequently assessed in an occupational therapy clinic.
Indicative DCD was found in 57 (81.4%) children with 22q11.2DS compared with 2 (6.3%) control siblings (odds ratio (OR) = 36.7, P < 0.001). Eight of nine (89%) children with indicative DCD met DSM-5 criteria for DCD. Poorer coordination was associated with increased numbers of anxiety, (P < 0.001), attention-deficit hyperactivity disorder (ADHD) (P < 0.001) and autism-spectrum disorder (ASD) symptoms (P < 0.001) in children with 22q11.2DS. Furthermore, 100% of children with 22q11.2DS and ADHD had indicative DCD (20 of 20), as did 90% of children with anxiety disorder (17 of 19) and 96% of children who screened positive for ASD (22 of 23). The Developmental Coordination Disorder Questionnaire score was related to sustained attention (P = 0.006), even after history of epileptic fits (P = 0.006) and heart problems (P = 0.009) was taken into account.
Clinicians should be aware of the high risk of coordination difficulties in children with 22q11.2DS and its association with risk of mental disorder and specific neurocognitive deficits.
This paper reports the first successful synthesis and the structural characterization of nanocrystalline and stacking-disordered β-cristobalite AlPO4 that is chemically stabilized down to room temperature and free of crystalline impurity phases. Several batches of the title compound were synthesized and thoroughly characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy, selected area electron diffraction, energy dispersive X-ray spectroscopy mapping in SEM, solid-state 31P nuclear magnetic resonance (31P-NMR) spectroscopy including the TRAPDOR method, differential thermal analysis (DTA), gas-sorption methods, optical emission spectroscopy, X-ray fluorescence spectroscopy, and ion chromatography. Parameters that are critical for the synthesis were identified and optimized. The synthesis procedure yields reproducible results and is well documented. A high-quality XRD pattern of the title compound is presented, which was collected with monochromatic copper radiation at room temperature in a wide 2θ range of 5°–100°.
Efforts to address health disparities and achieve health equity are critically dependent on the development of a diverse research workforce. However, many researchers from underrepresented backgrounds face challenges in advancing their careers, securing independent funding, and finding the mentorship needed to expand their research.
Faculty from the University of Maryland at College Park and the University of Wisconsin-Madison developed and evaluated an intensive week-long research and career-development institute—the Health Equity Leadership Institute (HELI)—with the goal of increasing the number of underrepresented scholars who can sustain their ongoing commitment to health equity research.
In 2010-2016, HELI brought 145 diverse scholars (78% from an underrepresented background; 81% female) together to engage with each other and learn from supportive faculty. Overall, scholar feedback was highly positive on all survey items, with average agreement ratings of 4.45-4.84 based on a 5-point Likert scale. Eighty-five percent of scholars remain in academic positions. In the first three cohorts, 73% of HELI participants have been promoted and 23% have secured independent federal funding.
HELI includes an evidence-based curriculum to develop a diverse workforce for health equity research. For those institutions interested in implementing such an institute to develop and support underrepresented early stage investigators, a resource toolbox is provided.
Here, we investigate the effect of divalent metal (Zn2+, Cd2+ and Hg2+) on the structural and optoelectronic properties of methylammonium lead iodide perovskite materials prepared by the two-step deposition process. The incorporation of Cd2+ significantly improved the grain size, crystallinity, and charge carrier lifetime of CH3NH3PbI3. The inclusion of Hg2+ and Zn2+ improved the grain size compare to the control sample but adversely affected the optoelectronic properties of perovskite films. The Hg- and Zn-based impurities were formed on the surface of the films, which increased the charge trap density and lead to high non-radiative recombination rate. Time resolved photoluminescence measurements indicated that the Cd and Zn point defects do not create deep-level trap states, but the Zn-modified film showed a low lifetime due to morphology changes in the film and particle segregation on the surface.
Following the approach of standard filtering theory, we analyse investor valuation of firms, when these are modelled as geometric-Brownian state processes that are privately and partially observed, at random (Poisson) times, by agents. Tasked with disclosing forecast values, agents are able purposefully to withhold their observations; explicit filtering formulae are derived for downgrading the valuations in the absence of disclosures. The analysis is conducted for both a solitary firm and m co-dependent firms.
The association between harmful use of alcohol and HIV infection is well documented. To address this dual epidemic, the US President's Emergency Plan for AIDS Relief (PEPFAR) developed and implemented a multi-pronged approach primarily in Namibia and Botswana. We present the approach and preliminary results of the public health investigative and programmatic activities designed, initiated and supported by PEPFAR to combat the harmful use of alcohol and its association as a driver of HIV morbidity and mortality from 2008 to 2013.
PEPFAR supported comprehensive alcohol programming using a matrix model approach that combined the socio-ecological framework and the Alcohol Misuse Prevention and Intervention Continuum. This structure enabled seven component objectives: (1) to quantify harmful use of alcohol through rapid assessments; (2) to develop and evaluate alcohol-based interventions; (3) to promote screening programs and alcohol abuse resource services; (4) to support stakeholder networks; (5) to support policy interventions and (6) structural interventions; and (7) to institutionalize universal prevention messages.
Targeted PEPFAR support for alcohol activities resulted in several projects to address harmful alcohol use and HIV. Components are graphically conceptualized within the matrix model, demonstrating the intersections between primary, secondary and tertiary prevention activities and individual, interpersonal, community, and societal factors. Key initiative successes included leveraging alcohol harm prevention activities that enabled projects to be piloted in healthcare settings, schools, communities, and alcohol outlets. Primary challenges included the complexity of multi-sectorial programming, varying degrees of political will, and difficulties monitoring outcomes over the short duration of the program.