Acceptability of a hypothetical dengue vaccine and the potential impact of dengue vaccination on personal vector control behavior: a qualitative study in Fortaleza, Brazil.

BACKGROUND: Dengue is the most rapidly spreading viral vector-borne disease in the world. Promising new dengue vaccines have contributed to a growing consensus that effective dengue control will require integrated strategies of vaccination and vector control. In this qualitative study, we explored the perspectives of residents of Fortaleza, Brazil on acceptability of a hypothetical safe and effective dengue vaccine, specific drivers of dengue vaccine acceptance or hesitance, and the expected impact of dengue vaccination on their personal vector control practices. METHODS: A total of 43 in-depth interviews were conducted from April to June 2022 with Fortaleza residents from a diverse range of educational and professional backgrounds, with and without recent personal experiences of symptomatic dengue infections. Data were analyzed using the principles of inductive grounded theory methodology. RESULTS: Our findings indicate that knowledge of dengue transmission, symptoms, and prevention methods was strong across respondents. Respondents described willingness to accept a hypothetical dengue vaccine for themselves and their children, while emphasizing that the vaccine must be demonstrably safe and effective. Respondents expressed diverse perspectives on how receiving a safe and effective dengue vaccine might influence their personal vector control behaviors, relating these behaviors to their perception of risk from other Aedes mosquito-carried infections and beliefs about the role of vector control in maintaining household cleanliness. CONCLUSIONS: Our study findings provide community-level perspectives on dengue vaccination and its potential impact on personal vector control behavior for policymakers and program managers in Fortaleza to consider as new dengue vaccines become available. With the introduction of any new dengue vaccine, community perspectives and emerging concerns that may drive vaccine hesitancy should be continuously sought out. Improved urban infrastructure and efforts to engage individuals and communities in vector control may be needed to optimize the impact of future dengue vaccinations and prevent rising cases of other arboviruses such as Zika and chikungunya.

Impact of 1,7-malaria reactive community-based testing and response (1,7-mRCTR) approach on malaria prevalence in Tanzania.

BACKGROUND: Progress in malaria control has stalled in recent years and innovative surveillance and response approaches are needed to accelerate malaria control and elimination efforts in endemic areas of Africa. Building on a previous China-UK-Tanzania pilot study on malaria control, this study aimed to assess the impact of the 1,7-malaria Reactive Community-Based Testing and Response (1,7-mRCTR) approach implemented over two years in three districts of Tanzania. METHODS: The 1,7-mRCTR approach provides community-based malaria testing via rapid diagnostic tests and treatment in villages with the highest burden of malaria incidence based on surveillance data from health facilities. We used a difference-in-differences quasi-experimental design with linear probability models and two waves of cross-sectional household surveys to assess the impact of 1,7-mRCTR on malaria prevalence. We conducted sensitivity analyses to assess the robustness of our results, examined how intervention effects varied in subgroups, and explored alternative explanations for the observed results. RESULTS: Between October 2019 and September 2021, 244,771 community-based malaria rapid tests were completed in intervention areas, and each intervention village received an average of 3.85 rounds of 1-7mRCTR. Malaria prevalence declined from 27.4% at baseline to 11.7% at endline in the intervention areas and from 26.0% to 16.0% in the control areas. 1,7-mRCTR was associated with a 4.5-percentage-point decrease in malaria prevalence (95% confidence interval: - 0.067, - 0.023), equivalent to a 17% reduction from the baseline. In Rufiji, a district characterized by lower prevalence and where larviciding was additionally provided, 1,7-mRCTR was associated with a 63.9% decline in malaria prevalence. CONCLUSIONS: The 1,7-mRCTR approach reduced malaria prevalence. Despite implementation interruptions due to the COVID-19 pandemic and supply chain challenges, the study provided novel evidence on the effectiveness of community-based reactive approaches in moderate- to high-endemicity areas and demonstrated the potential of South-South cooperation in tackling global health challenges.

A multistep mediation model examining how consultation in prolonged exposure therapy affects PTSD treatment outcomes.

Prolonged exposure therapy (PE) is an evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) that is underutilized in the military health system. Previous research suggests that postworkshop consultation is important for successful implementation. However, little is known about how consultation may relate to EBP adoption or patient outcomes. The present study addressed these gaps by examining associations between consultation, provider self-efficacy, use of PE, and patient outcomes using a multistep mediation model. This study used data from Foa et al. (2020), a two-armed randomized implementation trial comparing two PE training models: standard training (workshop only) and extended training (workshop + 6-8 months of postworkshop expert consultation) at three U.S. Army sites. Participants were patients with PTSD (N = 242) receiving care from the participating providers (N = 103). Providers who received extended training reported greater PE self-efficacy compared to standard training providers, but self-efficacy was unrelated to their use of PE components or to patient outcomes. Extended training providers used more PE components and had superior patient outcomes than standard training providers, and patient outcomes were mediated by the use of PE components. To our knowledge, this is the first study to demonstrate that EBP consultation leads to improved clinical outcomes for patients through increased use of the EBP. PE adoption (i.e., use of PE components in therapy) was not explained by increases in self-efficacy among providers who received extended training. Therefore, future research should assess how other factors may influence provider behavior in implementing EBPs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in the low endemic setting of Namibia: an analysis alongside a 2×2 factorial design cluster randomised controlled trial.

OBJECTIVES: To estimate the cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in a low endemic setting. SETTING: The study was part of a 2×2 factorial design cluster randomised controlled trial within the catchment area of 11 primary health facilities in Zambezi, Namibia. PARTICIPANTS: Cost and outcome data were collected from the trial, which included 8948 community members that received interventions due to their residence within 500 m of malaria index cases. OUTCOME MEASURES: The primary outcome was incremental cost effectiveness ratio (ICER) per in incident case averted. ICER per prevalent case and per disability-adjusted life years (DALY) averted were secondary outcomes, as were per unit interventions costs and personnel time. Outcomes were compared as: (1) rfMDA versus RACD, (2) RAVC versus no RAVC and (3) rfMDA+RAVC versus RACD only. RESULTS: rfMDA cost 1.1× more than RACD, and RAVC cost 1.7× more than no RAVC. Relative to RACD only, the cost of rfMDA+RAVC was double ($3082 vs $1553 per event). The ICERs for rfMDA versus RACD, RAVC versus no RAVC and rfMDA+RAVC versus RACD only were $114, $1472 and $842, per incident case averted, respectively. Using prevalent infections and DALYs as outcomes, trends were similar. The median personnel time to implement rfMDA was 20% lower than for RACD (30 vs 38 min per person). The median personnel time for RAVC was 34 min per structure sprayed. CONCLUSION: Implemented alone or in combination, rfMDA and RAVC were cost effective in reducing malaria incidence and prevalence despite higher implementation costs in the intervention compared with control arms. Compared with RACD, rfMDA was time saving. Cost and time requirements for the combined intervention could be decreased by implementing rfMDA and RAVC simultaneously by a single team. TRIAL REGISTRATION NUMBER: NCT02610400; Post-results.

Serological evaluation of the effectiveness of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia: Results from a secondary analysis of a cluster randomised trial.

BACKGROUND: Due to challenges in measuring changes in malaria at low transmission, serology is increasingly being used to complement clinical and parasitological surveillance. Longitudinal studies have shown that serological markers, such as Etramp5.Ag1, can reflect spatio-temporal differences in malaria transmission. However, these markers have yet to be used as endpoints in intervention trials. METHODS: Based on data from a 2017 cluster randomised trial conducted in Zambezi Region, Namibia, evaluating the effectiveness of reactive focal mass drug administration (rfMDA) and reactive vector control (RAVC), this study conducted a secondary analysis comparing antibody responses between intervention arms as trial endpoints. Antibody responses were measured on a multiplex immunoassay, using a panel of eight serological markers of Plasmodium falciparum infection - Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175, PfMSP119, PfAMA1, and PfGLURP.R2. FINDINGS: Reductions in sero-prevalence to antigens Etramp.Ag1, PfMSP119, Rh2.2030, and PfAMA1 were observed in study arms combining rfMDA and RAVC, but only effects for Etramp5.Ag1 were statistically significant. Etramp5.Ag1 sero-prevalence was significantly lower in all intervention arms. Compared to the reference arms, adjusted prevalence ratio (aPR) for Etramp5.Ag1 was 0.78 (95%CI 0.65 - 0.91, p = 0.0007) in the rfMDA arms and 0.79 (95%CI 0.67 - 0.92, p = 0.001) in the RAVC arms. For the combined rfMDA plus RAVC intervention, aPR was 0.59 (95%CI 0.46 - 0.76, p < 0.0001). Significant reductions were also observed based on continuous antibody responses. Sero-prevalence as an endpoint was found to achieve higher study power (99.9% power to detect a 50% reduction in prevalence) compared to quantitative polymerase chain reaction (qPCR) prevalence (72.9% power to detect a 50% reduction in prevalence). INTERPRETATION: While the observed relative reduction in qPCR prevalence in the study was greater than serology, the use of serological endpoints to evaluate trial outcomes measured effect size with improved precision and study power. Serology has clear application in cluster randomised trials, particularly in settings where measuring clinical incidence or infection is less reliable due to seasonal fluctuations, limitations in health care seeking, or incomplete testing and reporting. FUNDING: This study was supported by Novartis Foundation (A122666), the Bill & Melinda Gates Foundation (OPP1160129), and the Horchow Family Fund (5,300,375,400).

Allele-Specific Chemical Rescue of Histone Demethylases Using Abiotic Cofactors.

Closely related protein families evolved from common ancestral genes present a significant hurdle in developing member- and isoform-specific chemical probes, owing to their similarity in fold and function. In this piece of work, we explore an allele-specific chemical rescue strategy to activate a "dead" variant of a wildtype protein using synthetic cofactors and demonstrate its successful application to the members of the alpha-ketoglutarate (αKG)-dependent histone demethylase 4 (KDM4) family. We show that a mutation at a specific residue in the catalytic site renders the variant inactive toward the natural cosubstrate. In contrast, αKG derivatives bearing appropriate stereoelectronic features endowed the mutant with native-like demethylase activity while remaining refractory to a set of wild type dioxygenases. The orthogonal enzyme-cofactor pairs demonstrated site- and degree-specific lysine demethylation on a full-length chromosomal histone in the cellular milieu. Our work offers a strategy to modulate a specific histone demethylase by identifying and engineering a conserved phenylalanine residue, which acts as a gatekeeper in the KDM4 subfamily, to sensitize the enzyme toward a novel set of αKG derivatives. The orthogonal pairs developed herein will serve as probes to study the role of degree-specific lysine demethylation in mammalian gene expression. Furthermore, this approach to overcome active site degeneracy is expected to have general application among all human αKG-dependent dioxygenases.

The effects of a prolonged exposure workshop with and without consultation on provider and patient outcomes: a randomized implementation trial.

BACKGROUND: Prolonged exposure therapy (PE) is an evidence-based treatment for posttraumatic stress disorder (PTSD) that is underutilized in the military health system. Standard workshop training in PE may not be sufficient to alter provider behavior, but post-workshop consultation requires significant resources. Therefore, it is important to determine the incremental utility of post-workshop consultation. METHODS: This study used a hybrid type III randomized implementation trial at 3 US Army installations. Providers were randomized to receive a 4-day prolonged exposure workshop (Standard training condition, n = 60), or the prolonged exposure workshop followed by 6-8 months of post-workshop expert case consultation (Extended training condition, n = 43). The effects training condition were examined on provider attitudes (self-efficacy in delivering PE, expectations for patient improvement, and beliefs about PE), use of PE and PE components, and clinical outcomes of patients with PTSD (using the Clinician-Administered PTSD Scale (CAPS-5)). RESULTS: Extended condition providers reported greater improvements in self-efficacy, b = .83, 95% CI [.38, 1.27], t(79) = 3.71, p = .001, and d = .63. A greater proportion of patients in the Extended condition (44%) than in the Standard condition (27%) received at least 1 PE session, b = .76, t(233) = 2.53, p = .012, and OR = 2.13. Extended condition providers used more PE components (M = .9/session) than did Standard condition providers (M = .5/session), b = .54, 95% CI [.15, .93], t(68) = 2.70, p = .007, and d = .68. Finally, decrease in patients' PTSD symptoms was faster for patients of Extended condition providers than for patients of Standard condition providers, b = - 1.81, 95% CI [- 3.57, - .04], t(263) = - 2.02, p = .045, and d = .66, and their symptoms were lower at the second assessment, b = - 5.47, 95% CI [- 9.30, - 1.63], t(210) = - 2.81, p = .005, and d = .66. CONCLUSIONS: Post-workshop consultation improved self-efficacy for delivering PE, greater use of PE, faster PTSD reduction, and lower PTSD severity at the second assessment. To our knowledge, this is the first demonstration that post-workshop case consultation for PE improves patient outcomes. TRIAL REGISTRATION: Clinicaltrials.gov , NCT02982538 . Registered December 5, 2016; retrospectively registered.

Fixed dose rivaroxaban can be used in extremes of bodyweight: A population pharmacokinetic analysis.

BACKGROUND: Emerging safety and efficacy data for rivaroxaban suggest traditional therapy and rivaroxaban are comparable in the morbidly obese. However, real-world data that indicate pharmacokinetic (PK) parameters are comparable at the extremes of body size are lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee (ISTH SSC) suggests avoiding the use of direct oral anticoagulants (DOACs) in patients weighing >120 kg or with a body mass index >40 kg/m2 and gives no recommendation on the use of DOACs in those <50 kg. OBJECTIVES: To generate a population PK model to understand the influence of bodyweight on rivaroxaban exposure from clinical practice data. METHOD: Rivaroxaban plasma concentrations and patient characteristics were collated between 2013 and 2018 at King's College Hospital anticoagulation clinic. A population PK model was developed using a nonlinear mixed effects approach and then used to simulate rivaroxaban concentrations at the extremes of bodyweight. RESULTS: A robust population PK model derived from 913 patients weighing between 39 kg and 172 kg was developed. The model included data from n = 86 >120 kg, n = 74 BMI >40 kg/m2 , and n = 30 <50 kg. A one-compartment model with between-subject variability on clearance and a proportional error model best described the data. Creatinine clearance calculated by Cockcroft-Gault, with lean bodyweight as the weight descriptor in this equation, was the most significant covariate influencing rivaroxaban exposure. CONCLUSIONS: Our work demonstrates rivaroxaban can be used at extremes of bodyweight provided renal function is satisfactory. We recommend that the ISTH SSC revises the current guidance with respect to rivaroxaban at extremes of body size.

Effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of Namibia: a cluster-randomised controlled, open-label, two-by-two factorial design trial.

BACKGROUND: In low malaria-endemic settings, screening and treatment of individuals in close proximity to index cases, also known as reactive case detection (RACD), is practised for surveillance and response. However, other approaches could be more effective for reducing transmission. We aimed to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in the low malaria-endemic setting of Zambezi (Namibia). METHODS: We did a cluster-randomised controlled, open-label trial using a two-by-two factorial design of 56 enumeration area clusters in the low malaria-endemic setting of Zambezi (Namibia). We randomly assigned these clusters using restricted randomisation to four groups: RACD only, rfMDA only, RAVC plus RACD, or rfMDA plus RAVC. RACD involved rapid diagnostic testing and treatment with artemether-lumefantrine and single-dose primaquine, rfMDA involved presumptive treatment with artemether-lumefantrine, and RAVC involved indoor residual spraying with pirimiphos-methyl. Interventions were administered within 500 m of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitoes (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA plus RAVC vs RACD only), an intention-to-treat analysis was done. For each of the three comparisons, the primary outcome was the cumulative incidence of locally acquired malaria cases. This trial is registered with ClinicalTrials.gov, number NCT02610400. FINDINGS: Between Jan 1, 2017, and Dec 31, 2017, 55 enumeration area clusters had 1118 eligible index cases that led to 342 interventions covering 8948 individuals. The cumulative incidence of locally acquired malaria was 30·8 per 1000 person-years (95% CI 12·8-48·7) in the clusters that received rfMDA versus 38·3 per 1000 person-years (23·0-53·6) in the clusters that received RACD; 30·2 per 1000 person-years (15·0-45·5) in the clusters that received RAVC versus 38·9 per 1000 person-years (20·7-57·1) in the clusters that did not receive RAVC; and 25·0 per 1000 person-years (5·2-44·7) in the clusters that received rfMDA plus RAVC versus 41·4 per 1000 person-years (21·5-61·2) in the clusters that received RACD only. After adjusting for imbalances in baseline and implementation factors, the incidence of malaria was lower in clusters receiving rfMDA than in those receiving RACD (adjusted incidence rate ratio 0·52 [95% CI 0·16-0·88], p=0·009), lower in clusters receiving RAVC than in those that did not (0·48 [0·16-0·80], p=0·002), and lower in clusters that received rfMDA plus RAVC than in those receiving RACD only (0·26 [0·10-0·68], p=0·006). No serious adverse events were reported. INTERPRETATION: In a low malaria-endemic setting, rfMDA and RAVC, implemented alone and in combination, reduced malaria transmission and should be considered as alternatives to RACD for elimination of malaria. FUNDING: Novartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund.

Probing Ca2+-induced conformational change of calmodulin with gold nanoparticle-decorated single-walled carbon nanotube field-effect transistors.

Nanomaterials are ideal for electrochemical biosensors, with their nanoscale dimensions enabling the sensitive probing of biomolecular interactions. In this study, we compare field-effect transistors (FET) comprised of unsorted (un-) and semiconducting-enriched (sc-) single-walled carbon nanotubes (SWCNTs). un-SWCNTs have both metallic and semiconducting SWCNTs in the ensemble, while sc-SWCNTs have a >99.9% purity of semiconducting nanotubes. Both SWCNT FET devices were decorated with gold nanoparticles (AuNPs) and were then employed in investigating the Ca2+-induced conformational change of calmodulin (CaM) - a vital process in calcium signal transduction in the human body. Different biosensing behavior was observed from FET characteristics of the two types of SWCNTs, with sc-SWCNT FET devices displaying better sensing performance with a dynamic range from 10-15 M to 10-13 M Ca2+, and a lower limit of detection at 10-15 M Ca2+.

Allele-Specific Inhibition of Histone Demethylases.

Histone demethylases play a critical role in mammalian gene expression by removing methyl groups from lysine residues in degree- and site-specific manner. To specifically interrogate members and isoforms of this class of enzymes, we have developed demethylase variants with an expanded active site. The mutant enzymes are capable of performing lysine demethylation with wild-type proficiency, but are sensitive to inhibition by cofactor-competitive molecules embellished with a complementary steric "bump". The selected inhibitors show more than 20-fold selectivity over the wild-type demethylase, thus overcoming issues typical to pharmacological and genetic approaches. The mutant-inhibitor pairs are shown to act on a physiologically relevant full-length substrate. By engineering a conserved amino acid to achieve member-specific perturbation, this study provides a general approach for studying histone demethylases in diverse cellular processes.

Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease characterised by occlusive pulmonary vasculopathy. Activation of bone morphogenetic protein receptor 2 (BMPR2) signalling by FK506 (tacrolimus) reverses occlusive vasculopathy in rodent PAH models. Here, we determined the safety and tolerability of low-level FK506 therapy in stable PAH patients.We performed a randomised, double-blind, placebo-controlled, 16-week, single-centre, phase IIa trial in PAH patients with New York Heart Association functional class II/III symptoms using three FK506 target levels (<2, 2-3 and 3-5 ng·mL-1). 23 patients were randomised and 20 patients completed the trial.FK506 was generally well tolerated, with nausea/diarrhoea being the most commonly reported adverse event and no observation of line infections in patients on intravenous prostacyclin therapy. PAH patients had significantly lower BMPR2 expression in peripheral blood mononuclear cells versus healthy controls (n=13; p=0.005), which improved after FK506 treatment. While we observed that some patients responded with a pronounced increase in BMPR2 expression as well as improvement in 6-min walk distance, and serological and echocardiographic parameters of heart failure, these changes were not significant.Low-level FK506 is well tolerated and increases BMPR2 in subsets of PAH patients. These results support the study of FK506 in a phase IIb efficacy trial.

The implementation of prolonged exposure: Design of a multisite study evaluating the usefulness of workshop with and without consultation.

This randomized trial examines the dissemination and implementation of prolonged exposure (PE) therapy for posttraumatic stress symptoms in U.S. Army medical treatment facilities. The study compares two PE training models: Standard PE training, comprised of a 4-day workshop only, and Extended PE training, comprised of a 4-day workshop plus expert case consultation. Behavioral health providers (N=180) across three medium-to-large Army installations will be randomly assigned to either Standard PE training or Extended PE training. Changes in provider attitudes will be examined across groups. After completing PE training, the use of PE components with patients reporting posttraumatic stress symptoms and clinical outcomes of these participating patients (N=500) will be examined. This article describes the rationale and methods of the study. In addition, a number of methodological issues in conducting a multisite naturalistic study in the U.S. Army are discussed.

Expanding access to parasite-based malaria diagnosis through retail drug shops in Tanzania: evidence from a randomized trial and implications for treatment.

BACKGROUND: Tanzania has seen a reduction in the fraction of fevers caused by malaria, likely due in part to scale-up of control measures. While national guidelines require parasite-based diagnosis prior to treatment, it is estimated that more than half of suspected malaria treatment-seeking in Tanzania initiates in the private retail sector, where diagnosis by malaria rapid diagnostic test (RDT) or microscopy is illegal. This pilot study investigated whether the introduction of RDTs into Accredited Drug Dispensing Outlets (ADDOs) under realistic market conditions would improve case management practices. METHODS: Dispensers from ADDOs in two intervention districts in Tanzania were trained to stock and perform RDTs and monitored quarterly. Each district was assigned a different recommended retail price to evaluate the need for a subsidy. Malaria RDT and artemisinin-based combination therapy (ACT) uptake and availability were measured pre-intervention and 1 year post-intervention through structured surveys of ADDO owners and exiting customers in both intervention districts and one contiguous control district. Descriptive analysis and logistic regression were used to compare the three districts and identify predictive variables for testing. RESULTS AND DISCUSSION: A total of 310 dispensers from 262 ADDOs were trained to stock and perform RDTs. RDT availability in intervention ADDOs increased from 1% (n = 172) to 73% (n = 163) during the study; ACT medicines were available in 75% of 260 pre-intervention and 68% of 254 post-intervention ADDOs. Pre-treatment testing performed within the ADDO increased from 0 to 65% of suspected malaria patients who visited a shop (95% CI 60.8-69.6%) with no difference between intervention districts. Overall parasite-based diagnosis increased from 19 to 74% in intervention districts and from 3 to 18% in the control district. Prior knowledge of RDT availability (aOR = 1.9, p = 0.03) and RDT experience (aOR = 1.9, p = 0.01) were predictors for testing. Adherence data indicated that 75% of malaria positives received ACT, while 3% of negatives received ACT. CONCLUSIONS: Trained and supervised ADDO dispensers in rural Tanzania performed and sold RDTs under real market conditions to two-thirds of suspected malaria patients during this one-year pilot. These results support the hypothesis that introducing RDTs into regulated private retail sector settings can improve malaria testing and treatment practices without an RDT subsidy. Trial registration ISRCTN ISRCTN14115509.

Robust CNT field emitters: patterning, growth, transfer, and in situ anchoring.

Robust carbon nanotube (CNT)-based cold cathodes were fabricated on titanium (Ti) substrates. Methods to grow vertically aligned CNTs  directly on Ti substrates were developed. These cathodes can be treated post-growth at elevated temperatures under inert atmosphere which causes the surface-grown CNTs to become anchored to the substrate surface. These samples offer improvements in field emission properties over previously studied silicon (Si) substrate-based cathodes with no anchoring, displaying low threshold voltages, high field enhancement factors, and long operating lifetimes. Current densities of 25 mA cm-2 were held for over 24 h with anchored samples at low electric fields (observed thresholds as low as 0.5 V µm-1) and more current stability. Higher current densities of up to 150 mA cm-2 could be reached with anchored samples, limited only by the experimental setup. In efforts to generate even more stable and reproducible field emission, a transfer process of CNTs from polished Si to Ti with copper (Cu) was developed (flipCNTs). These cathodes display extreme improvements over previous results, with observed thresholds as low as 0.2 V µm-1 and γ-factors as high as 30 000. To demonstrate the utility of these robust cathodes, a flipCNT-based cathode was assembled into a fully functioning vacuum triode.

The hazards of off-road motor sports: Are four wheels better than two?

BACKGROUND: Off-road motorsports are an increasing popular activity, yet the relative safety profile of all-terrain vehicles (ATV) to off-road motorcycles (ORMC) has not been compared. STUDY DESIGN: A retrospective review of the 2002-2006 US National Trauma Data Bank of ATV and ORMC crash victims. Patients were described according to demographic (age, sex, race and ethnicity, insurance status) and injury characteristics (Injury Severity Score, hypotension, motor component of the Glasgow Coma Score, presence of a severe head or extremity injury) known to affect trauma outcomes. Logistic regression evaluated the independent effect of an ATV vehicle on mortality, intensive care unit (ICU) admission, and placement on a ventilator relative to ORMC. The anatomic distribution of severe injuries was compared between survivors and decedents within each vehicle type. RESULTS: A total of 34,457 patients met inclusion criteria, of whom, 24,582 were ATV patients and 9875 were ORMC patients. ATV patients had 51% higher risk-adjusted odds of death (OR 1.51; 95% CI 1.03-2.20), 55% higher risk-adjusted odds of being admitted to an ICU (OR 1.55; 95% CI 1.42-1.70), and 42% higher risk-adjusted odds of being placed on a ventilator (OR 1.42, 95% CI 1.17-1.72) compared to ORMC crash victims. Decedents in both vehicle types were more likely to suffer severe head, thoracic, and abdominal injuries relative to their surviving counterparts. CONCLUSION: For injured riders, ATVs are associated with increased mortality and higher resource utilisation compared to ORMCs. Both groups suffer distinct anatomic injuries, suggesting the need for focused areas of injury prevention planning and research.

Community Health Workers' Provision of Family Planning Services in Low- and Middle-Income Countries: A Systematic Review of Effectiveness.

This systematic review evaluates the strength of the evidence that community health workers' (CHW) provision of family planning (FP) services in low- and middle-income countries is effective. In a search of eight databases, articles were screened by study design and outcome measure and ranked by strength of evidence. Only randomized trials, longitudinal studies with a comparison group, and pre-test/post-test studies met inclusion criteria. A total of 56 studies were included. Of those studies with relevant data, approximately 93 percent indicated that CHW FP programs effectively increased the use of modern contraception, while 83 percent reported an improvement in knowledge and attitudes concerning contraceptives. Based on these findings, strong evidence exists for promoting CHW programs to improve access to FP services. We recommend a set of best practice guidelines that researchers and program managers can use to report on CHW FP programs to facilitate the translation of research to practice across a wide range of settings.

Amine Analysis Using AlexaFluor 488 Succinimidyl Ester and Capillary Electrophoresis with Laser-Induced Fluorescence.

Fluorescent probes enable detection of otherwise nonfluorescent species via highly sensitive laser-induced fluorescence. Organic amines are predominantly nonfluorescent and are of analytical interest in agricultural and food science, biomedical applications, and biowarfare detection. Alexa Fluor 488 N-hydroxysuccinimidyl ester (AF488 NHS-ester) is an amine-specific fluorescent probe. Here, we demonstrate low limit of detection of long-chain (C9 to C18) primary amines and optimize AF488 derivatization of long-chain primary amines. The reaction was found to be equally efficient in all solvents studied (dimethylsulfoxide, ethanol, and N,N-dimethylformamide). While an organic base (N,N-diisopropylethylamine) is required to achieve efficient reaction between AF488 NHS-ester and organic amines with longer hydrophobic chains, high concentrations (>5 mM) result in increased levels of ethylamine and propylamine in the blank. Optimal incubation times were found to be >12 hrs at room temperature. We present an initial capillary electrophoresis separation for analysis using a simple micellar electrokinetic chromatography (MEKC) buffer consisting of 12 mM sodium dodecylsulfate (SDS) and 5 mM carbonate, pH 10. Limits of detection using the optimized labeling conditions and these separation conditions were 5-17 nM. The method presented here represents a novel addition to the arsenal of fluorescent probes available for highly sensitive analysis of small organic molecules.

Unconscious Race and Class Biases among Registered Nurses: Vignette-Based Study Using Implicit Association Testing.

BACKGROUND: Implicit bias is an unconscious preference for a specific social group that can have adverse consequences for patient care. Acute care clinical vignettes were used to examine whether implicit race or class biases among registered nurses (RNs) impacted patient-management decisions. STUDY DESIGN: In a prospective study conducted among surgical RNs at the Johns Hopkins Hospital, participants were presented 8 multi-stage clinical vignettes in which patients' race or social class were randomly altered. Registered nurses were administered implicit association tests (IATs) for social class and race. Ordered logistic regression was then used to examine associations among treatment differences, race, or social class, and RN's IAT scores. Spearman's rank coefficients comparing RN's implicit (IAT) and explicit (stated) preferences were also investigated. RESULTS: Two hundred and forty-five RNs participated. The majority were female (n=217 [88.5%]) and white (n=203 [82.9%]). Most reported that they had no explicit race or class preferences (n=174 [71.0%] and n=108 [44.1%], respectively). However, only 36 nurses (14.7%) demonstrated no implicit race preference as measured by race IAT, and only 16 nurses (6.53%) displayed no implicit class preference on the class IAT. Implicit association tests scores did not statistically correlate with vignette-based clinical decision making. Spearman's rank coefficients comparing implicit (IAT) and explicit preferences also demonstrated no statistically significant correlation (r=-0.06; p=0.340 and r=-0.06; p=0.342, respectively). CONCLUSIONS: The majority of RNs displayed implicit preferences toward white race and upper social class patients on IAT assessment. However, unlike published data on physicians, implicit biases among RNs did not correlate with clinical decision making.

Outcomes of trauma care at centers treating a higher proportion of older patients: the case for geriatric trauma centers.

BACKGROUND: The burden of injury among older patients continues to grow and accounts for a disproportionate number of trauma deaths. We wished to determine if older trauma patients have better outcomes at centers that manage a higher proportion of older trauma patients. METHODS: The National Trauma Data Bank years 2007 to 2011 was used. All high-volume Level 1 and Level 2 trauma centers were included. Trauma centers were categorized by the proportion of older patients seen. Adult trauma patients were categorized as older (≥65 years) and younger adults (16-64 years). Coarsened exact matching was used to determine differences in mortality and length of stay between older and younger adults. Risk-adjusted mortality ratios by proportion of older trauma patients seen were analyzed using multivariate logistic regression models and observed-expected ratios. RESULTS: A total of 1.9 million patients from 295 centers were included. Older patients accounted for one fourth of trauma visits. Matched analysis revealed that older trauma patients were 4.2 times (95% confidence interval, 3.99-4.50) more likely to die than younger patients. Older patients were 34% less likely to die if they presented at centers treating a high versus low proportion of older trauma (odds ratio, 0.66; 95% confidence interval, 0.54-0.81). These differences were independent of trauma center performance. CONCLUSION: Geriatric trauma patients treated at centers that manage a higher proportion of older patients have improved outcomes. This evidence supports the potential advantage of treating older trauma patients at centers specializing in geriatric trauma. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.