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The NOAA Global Monitoring Laboratory (GML) measures atmospheric hydrogen (H2) in grab samples collected weekly as flask pairs at over 50 sites in the Cooperative Global Air Sampling Network. Measurements representative of background air sampling show higher H2 in recent years at all latitudes. The marine boundary layer (MBL) global mean H2 was 552.8 ppb in 2021, 20.2 ± 0.2 ppb higher compared to 2010. A 10 ppb or more increase over the 2010–2021 average annual cycle was detected in 2016 for MBL zonal means in the tropics and in the Southern Hemisphere. Carbon monoxide measurements in the same-air samples suggest large biomass burning events in different regions likely contributed to the observed interannual variability at different latitudes. The NOAA H2 measurements from 2009 to 2021 are now based on the World Meteorological Organization Global Atmospheric Watch (WMO GAW) H2 mole fraction calibration scale, developed and maintained by the Max Planck Institute for Biogeochemistry (MPI-BGC), Jena, Germany. GML maintains eight H2 primary calibration standards to propagate the WMO scale. These are gravimetric hydrogen-in-air mixtures in electropolished stainless steel cylinders (Essex Industries, St. Louis, MO), which are stable for H2. These mixtures were calibrated at the MPI-BGC, the WMO Central Calibration Laboratory (CCL) for H2, in late 2020 and span the range 250–700 ppb. We have used the CCL assignments to propagate the WMO H2 calibration scale to NOAA air measurements performed using gas chromatography and helium pulse discharge detector instruments since 2009. To propagate the scale, NOAA uses a hierarchy of secondary and tertiary standards, which consist of high-pressure whole-air mixtures in aluminum cylinders, calibrated against the primary and secondary standards, respectively. Hydrogen at the parts per billion level has a tendency to increase in aluminum cylinders over time. We fit the calibration histories of these standards with zero-, first-, or second-order polynomial functions of time and use the time-dependent mole fraction assignments on the WMO scale to reprocess all tank air and flask air H2 measurement records. The robustness of the scale propagation over multiple years is evaluated with the regular analysis of target air cylinders and with long-term same-air measurement comparison efforts with WMO GAW partner laboratories. Long-term calibrated, globally distributed, and freely accessible measurements of H2 and other gases and isotopes continue to be essential to track and interpret regional and global changes in the atmosphere composition. The adoption of the WMO H2 calibration scale and subsequent reprocessing of NOAA atmospheric data constitute a significant improvement in the NOAA H2 measurement records.

Objectives: This paper examines the role of antibiotics in treatment of Crohn’s Disease by investigating clinical trials done on the matter. We found antibiotic therapy to be effective in inducing remission or favorable clinical response in adults with active disease. The aim of the study is to perform a meta-analysis on the ability of antibiotics to induce remission or a favorable clinical response in Crohn’s Disease (CD) patients. Materials and Methods: A meta-analysis of randomized, double-blind, placebo-controlled trials of antibiotics for treatment of CD in adults was conducted. Odds ratio and probability difference were performed to estimate risk difference. The Number Needed to Treat (NNT) was also calculated for each antibiotic reviewed (rifaximin, metronidazole, clarithromycin, and ciprofloxacin). Results: Thirty-six clinical trial studies were identified, including 3346 patients. Twelve studies reported remission (defined as a CDAI < 150, or authors’ definition) while 24 reported solely a clinical response (defined as a decrease in CDAI or authors’ definition) upon completing an antibiotic regimen. Antibiotics greatly improved patients’ Crohn’s disease activity, with a total response (defined as clinical response plus remission) odds ratio of 1.85 (95% CI: 1.41-2.43), a clinical response odds ratio of 1.87 (95% CI: 1.48-2.37), and a remission odds ratio of 1.90 (95% CI: 1.40-2.57). The Number Needed to Treat for each of the antibiotics used in the clinical trials were 4.17 (Ciprofloxacin), 7.14 (Clarithromycin), 7.14 (Metronidazole), and 9.09 (Rifaximin). Conclusions: The odds of a Crohn’s Disease patient getting better is higher among those who take antibiotics most notably used in treating Inflammatory Bowel Disease than in placebo. This is an important outcome because it not only opens up a new treatment option for those suffering from Crohn’s Disease, but it also leads credibility to the theory that Crohn’s is caused, at least in part, by bacteria, such as Mycobacterium avium subspecies paratuberculosis (MAP) and adherent-invasive Escherichia coli (AIEC).

Abstract Background Eating can be a significant challenge for cancer survivors; however, to date there is no systematic way of assessing and addressing food related quality of life in this group. The purpose of our study was to develop a framework for doing so. Methods Over the course of 6 years in participant-led food workshops, we worked alongside 25 head and neck cancer (HNC) survivors and their partners, employing video-reflexive ethnographic (VRE) methods. The current study reports on data from the two summative workshops of this series where we worked with participants to cohere the emergent themes. Video and transcripts were reviewed and coded with participants and stakeholders according to domains of life that were affected by food. Three of the authors, one of whom is both survivor and researcher, arrived at the consensus framework. Results Seven areas of life were identified as affecting, or being affected by, altered eating. Three were physiological: anatomical, functional and sensory. Two captured the cognitive and behavioural labour of eating. Social life and identity were altered. The foregoing had an enduring emotional impact. Conclusions Altered eating has physical, emotional and social consequences. The altered eating framework provides a systematic way of exploring those consequences with individual survivors. This framework has the potential to improve both the assessment and treatment of altered eating, to benefit food-related quality of life.

Recent observations have detected surface active organics in atmospheric aerosols. We have studied the reaction of N2O5 on aqueous natural seawater and NaCl aerosols as a function of sodium dodecyl sulfate (SDS) concentration to test the effect of varying levels of surfactant on gas-aerosol reaction rates. SDS was chosen as a proxy for naturally occurring long chain monocarboxylic acid molecules, such as palmitic or stearic acid, because of its solubility in water and well-characterized surface properties. Experiments were performed using a newly constructed aerosol flow tube coupled to a chemical ionization mass spectrometer for monitoring the gas phase, and a differential mobility analyzer/condensation particle counter for determining aerosol surface area. We find that the presence of ~3.5wt% SDS in the aerosol, which corresponds to a monolayer surface coverage of ~2×1014 molecules cm-2, suppresses the N2O5 reaction probability, γN2O5, by approximately a factor of ten, independent of relative humidity. Consistent with this observation is a similar reduction in the rate of ClNO2 product generation measured simultaneously. However, the product yield remains nearly constant under all conditions. The degree of suppression is strongly dependent on SDS content in the aerosol, with no discernable effect at 0.1wt% SDS, but significant suppression at what we predict to be submonolayer coverages with 0.3–0.6wt% SDS on NaCl and natural seawater aerosols, respectively.

Objective: A pilot study was conducted to determine the current scope of practice of South African physiotherapists working in intensive care units in the government and the private sectors. These findings were compared to the findings from a European survey with regard to the role of the physiotherapist in European intensive care units. Methodology: Ninety questionnaires were distributed nationwide to secondary and tertiary government hospitals as well as to private practitioners involved in cardiopulmonary physiotherapy. The private practitioners included in this survey were listed in the Private Practitioners Association Official Members Directory. Junior and senior physiotherapists working in the intensive care units of their respective hospitals participated in completing the questionnaire. Comparisons between government and private sector data and between the South African survey and the European survey were carried out using the 2test for non-parametric data. A p-value of less than 0.05 was considered to be statistically significant. Results: Fifty-four questionnaires were analyzed and represented 60% of questionnaires sent out. Respondents to the South African survey reported 28% percent of all ICUs had between 9 - 12 beds; 83% physiotherapists indicated the availability of an on-call service during the night and 96% physiotherapists had a weekend physiotherapy service. Ninety-two percent of physiotherapists working in the government sector supervised students compared to 44% of physiotherapists in the private sector. Between 9% and 27% of physiotherapists in government and private hospitals actively participated in research in ICU. There were no statistically significant differences in the use of respiratory physiotherapy, mobilization and positioning between respondents to the European survey and those of the South African survey respectively. Conclusion: The response rate to this questionnaire was good. It was evident from this pilot survey that the scope of practice of physiotherapy in ICU didn’t differ significantly between the government and private sector in South Africa. The role of the intensive care physiotherapist in South Africa was similar to that of the European physiotherapist working in ICU.

In this study standard patterns of cerebral perfusion based on classifications described in the literature have been chosen and the ability of experienced imaging specialists to categorise the 99mTc HMPAO SPECT scans of patients referred to the department for investigation of dementia has been compared before and after the calculation of Statistical Parametric Maps (SPM—Wellcome Dept of Cognitive Neurology). The primary aim was to investigate whether SPM is an effective decision aid and whether it impacts on the confidence of image reporting. The secondary aim was to examine the influence of SPM on the agreement between image reporting and clinical diagnosis. The results showed that there was a slight decrease in agreement between the imaging specialists after the introduction of additional information from SPM (K = 0.57 to K = 0.5) and that agreement between imaging reporting (including information from SPM) and clinical diagnosis was moderate (K = 0.28). This study was able to confirm that SPM is capable of producing meaningful significance maps of individual patients in a routine clinical environment. However, there was no overwhelming evidence that SPM was able to resolve many of the dilemmas associated with the use of SPECT for the differential diagnosis of dementia. In particular, interpretation of SPECT perfusion patterns in dementia is a bigger problem than the initial identification of abnormalities.

The spider conch, Lambis lambis is one of the important fishery resources in the Vellapatti Village, Tuticorin, Southeast Coast of India. These conches land as by catches from crab nets (a modified bottom set gill net). The meat of gastropods is considered as a delicacy, rich in protein and the fat content is very low. Only a small section of the fisher folk consume its flesh, as it is less popular among the coastal fisher folk. For the utilization of this meat, chutney powder (a side dish for Idli or Dhosai in South India) was prepared from the meat. Biochemical, microbiological and sensory analyses were made to assess the shelf life for a period of four months. The meat had a protein content of 5.2%, 0.5% of carbohydrate and lipid content of 1%. The shelf life assessment of the chutney powder for a period of four months was carried out and it was found out that the product was good until the end of the assessment period. Even the TMA and TVB levels were found to be within the limits (10.8 mg per 100g and 18.36 mg per 100g, respectively). The present work reveals that the chutney powder is microbiologically and organoleptically good until the end of the storage period and safe for human consumption.

A community-based crab-fattening project was adopted by the womenfolk of Vellapatti fishing village in Tuticorin coast, Gulf of Mannar for proper utilization of their available resources and their leisure time for income generation. The mud crab, Scylla serrata and blue swimming crab, Portunus pelagicus were chosen for crab fattening which is ‘First of its kind’ in India and the women are successful in fattening and creating alternate income through this project. Between these two crabs, fattening of P. pelagicus is more attractive due to the short fattening span and the low price quoted on molted crabs at the auction sheds. The participation of women and the effectiveness of this project are discussed in this paper.

Abstract Chronic, non-communicable diseases present a major barrier to living a long and healthy life. In many cases, early diagnosis can facilitate prevention, monitoring, and treatment efforts, improving patient outcomes. There is therefore a critical need to make screening techniques as accessible, unintimidating, and cost-effective as possible. The association between ocular biomarkers and systemic health and disease (oculomics) presents an attractive opportunity for detection of systemic diseases, as ophthalmic techniques are often relatively low-cost, fast, and non-invasive. In this review, we highlight the key associations between structural biomarkers in the eye and the four globally leading causes of morbidity and mortality: cardiovascular disease, cancer, neurodegenerative disease, and metabolic disease. We observe that neurodegenerative disease is a particularly promising target for oculomics, with biomarkers detected in multiple ocular structures. Cardiovascular disease biomarkers are present in the choroid, retinal vasculature, and retinal nerve fiber layer, and metabolic disease biomarkers are present in the eyelid, tear fluid, lens, and retinal vasculature. In contrast, only the tear fluid emerged as a promising ocular target for the detection of cancer. The retina is a rich source of oculomics data, the analysis of which has been enhanced by artificial intelligence-based tools. Although not all biomarkers are disease-specific, limiting their current diagnostic utility, future oculomics research will likely benefit from combining data from various structures to improve specificity, as well as active design, development, and optimization of instruments that target specific disease signatures, thus facilitating differential diagnoses.

Abstract As AI systems proliferate, their greenhouse gas emissions are an increasingly important concern for human societies. In this article, we present a comparative analysis of the carbon emissions associated with AI systems (ChatGPT, BLOOM, DALL-E2, Midjourney) and human individuals performing equivalent writing and illustrating tasks. Our findings reveal that AI systems emit between 130 and 1500 times less CO2e per page of text generated compared to human writers, while AI illustration systems emit between 310 and 2900 times less CO2e per image than their human counterparts. Emissions analyses do not account for social impacts such as professional displacement, legality, and rebound effects. In addition, AI is not a substitute for all human tasks. Nevertheless, at present, the use of AI holds the potential to carry out several major activities at much lower emission levels than can humans.

Abstract Space weather has the potential to impact ground-based technologies on Earth, affecting many systems including railway signalling. This study uses a recently developed model to analyse the impact of geomagnetically induced currents on railway signalling systems in the United Kingdom during the March 1989 and October 2003 geomagnetic storms. The March 1989 storm is also scaled to estimate a 1-in-100 year and a 1-in-200 year extreme storm. Both the Glasgow to Edinburgh line, and the Preston to Lancaster section of the West Coast Main Line are modelled. No “right side” failures (when unoccupied sections appear occupied) are suggested to have occurred during either storm, and the total number of potential “wrong side” failures (when occupied sections appear clear) is low. However, the modelling indicates “right side” and “wrong side” failures are possible on both routes during the 1-in-100 year and 1-in-200 year extreme storms, with the Glasgow to Edinburgh line showing more total misoperations than the Preston to Lancaster section of the West Coast Main Line. A 1-in-100 year or 1-in-200 year extreme storm would result in misoperations over an extended period of time, with most occurring over a duration of 2–3 h either side of the peak of the storm.

Background: Plant-based formulas have become increasingly popular due to their health benefits, environmental concerns, cultural beliefs, improved palatability, and decreased cost. A retrospective chart review of medically stable children transitioning from a hypoallergenic formula to a yellow pea protein plant-based formula (PPPBF) was included. This study aimed to assess gastrointestinal tolerance, weight changes, and adherence to receiving a unique PPPBF. Methods: Healthcare providers (HCPs) from pediatric clinics across the United States who requested increased PPPBF samples between the dates of 1 November 2021and 31 January 2022 and again from 1 February 2022 to 15 April 2022 inputted survey data. The HCPs selected participants based on the inclusion criteria. Results: Seventy-three completed patient surveys were included of children (ages 1–18 years old, 41% females, 59% males). After the transition to PPPBF, 38.4% experienced improvement in GI tolerance, 56.2% experienced no change, and 5.5% reported worsening GI tolerance. There was a 95% adherence rate, and 98.9% reported no adverse reactions or allergic manifestations after formula transition. Conclusions: Transitioning from a hypoallergenic formula to a PPPBF showed a trend toward stable GI tolerance, weight gain or stability, and adherence. A PPPBF offers a first-choice option for children who are on hypoallergenic formulas due to intolerance.

BackgroundAdults with chronic health conditions need support to manage modifiable risk factors such as physical inactivity and poor diet. Disease-specific websites with health information on physical activity and diet quality may be effective in supporting adults in managing their chronic illnesses. ObjectiveThe primary aim of this review was to determine whether using websites with health information can lead to improvements in physical activity levels or diet quality in adults with chronic health conditions. MethodsRandomized controlled trials evaluating the effectiveness of website use on levels of physical activity or diet quality in adults with chronic health conditions were included. MEDLINE, Embase, CINAHL, and the Physiotherapy Evidence Database were searched from the earliest available record until February 2023. Data for outcomes measuring physical activity levels; diet quality; and, where reported, self-efficacy and quality of life were independently extracted by 2 reviewers. The risk of bias was assessed using the Physiotherapy Evidence Database scale, and the overall certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Where values were presented as the same unit of measure, postintervention scores were pooled for meta-analysis to yield an overall mean difference (MD). A standardized MD (SMD) was calculated for the pooled data in which different units for the same outcome were used. Individual trial data were described in cases where the data of trials could not be pooled. ResultsA total of 29 trials (N=6418 participants) across 8 different disease groups with intervention periods ranging from 4 weeks to 12 months were included in the analysis. There was moderate-certainty evidence that using websites with health information increased levels of moderate to vigorous physical activity (MD=39 min/wk, 95% CI 18.60-58.47), quality of life (SMD=0.36, 95% CI 0.12-0.59), and self-efficacy (SMD=0.26, 95% CI 0.05-0.48) and high-certainty evidence for reduction in processed meat consumption (MD=1.1 portions/wk, 95% CI 0.70-1.58) when compared with usual care. No differences were detected in other measures of diet quality. There was no increased benefit for website users who were offered additional support. ConclusionsThe use of websites for risk factor management has the potential to improve physical activity levels, quality of life, and self-efficacy as well as reduce processed meat consumption for adults living with chronic health conditions when compared with usual care. However, it remains unclear whether using websites leads to meaningful and long-lasting behavior change. Trial RegistrationPROSPERO CRD42021283168; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283168

Abstract Chronic obstructive pulmonary disease (COPD) has been reported as a potential risk factor for developing herpes zoster (HZ). We aimed at comparing incidence rates of HZ between people with versus without COPD in the US. This retrospective cohort study used data from Optum's de‐identified Clinformatics Data Mart database from 1/1/2013 through 12/31/2018. We identified two cohorts of people ≥40 years without prior HZ, HZ vaccination, postherpetic neuralgia (PHN) or HZ ophthalmicus: those with (COPD+) and those without (COPD−) a COPD diagnosis. Adjusted incidence rate ratios (aIRRs) of HZ and PHN were calculated using generalized linear models, controlling for the propensity score of being diagnosed with COPD and relevant demographic and clinical characteristics. People in the COPD+ cohort (n = 161 970) were considerably older, had more comorbidities and were more likely to use corticosteroids than those in the COPD− cohort (n = 9 643 522). The incidence rate of HZ was 5.7‐fold higher in the COPD+ versus COPD− cohorts (13.0 vs. 2.3 per 1000 person‐years [PY]; aIRR, 2.77; 95% confidence interval [CI], 2.69 to 2.85; P

Wildlife conservation in the Anthropocene requires bold conservation solutions including restoration of ecosystems and species. The recovery of large carnivore populations is a conservation goal which can generate significant benefits in terms of ecosystem services, ecological functionality, and human well-being. Tigers Panthera tigris, Asia’s most iconic species, are currently restricted to less than 10% of their historic range with recent national extinctions from a number of countries in mainland Southeast Asia. Tiger recovery through range expansion requires suitable habitat, a robust prey base, and high levels of institutional support for conservation. We explored government support for conservation to produce a ranking of the political opportunities for tiger restoration across current and former tiger range countries. We used this analysis, in combination with globally remotely sensed data-sets on human impact, to show that there is potential for significant tiger range expansion. We identified large expanses of currently unoccupied, but potentially suitable, habitat in at least 14 countries including all extant tiger range countries and four countries with extirpated tiger populations – Cambodia, Lao PDR, Viet Nam, and Kazakhstan. Thirty-two percent of expansion areas were within 50-km, and 50% within 100-km, of current tiger populations highlighting that in many landscapes range expansion could be driven by the natural dispersal of tigers provided connectivity is maintained or enhanced. The proportion of potential range within existing protected areas varied between 60% in Thailand and Cambodia. As such socially appropriate conservation approaches, in collaboration with local communities, will be necessary to support tiger recovery in many areas. We recommend that some of the areas which we have identified should be highlighted as significant for future tiger conservation by tiger range country governments. Whilst the landscapes and sites which we identify will require detailed ground-truthing, and all tiger reintroductions need extensive planning and feasibility assessments, safeguarding these areas for human-carnivore coexistence could provide significant planetary benefits and support both tiger recovery and Global Sustainable Development Goals.

Abstract Background The novel coronavirus pandemic (COVID-19) has had severe impacts on morbidity and mortality globally. Methods This study was set in rural central Kentucky and included participants recruited from public spaces. Fifteen qualitative interviews about personal experiences during the COVID-19 pandemic were conducted by phone from July 3 to July 24, 2020. Interviews were recorded, transcribed, and coded using a grounded theory approach. Results Participants who perceived COVID-19 to be a severe risk tended to have personal health concerns and therefore reported taking protective measures for themselves. A slightly smaller proportion of participants reported taking measures to protect others (particularly family). A minority of participants had an ambivalent attitude towards the risk and only took measures if required. COVID-19 vaccine acceptability was low with most participants expressing concerns regarding their need for a vaccine, safety of this vaccine, the value of personal rights, or future vaccine supply. Conclusions Most participants perceived some risk of COVID-19 and took steps to prevent infections in themselves and others. Mandates for mask use in certain locations were additionally useful for those who had an ambivalent attitude towards the risk of illness. There was surprisingly little connection between perceiving COVID-19 risk and a desire for the COVID-19 vaccine. In this setting, vaccine acceptability was low, with vaccine concerns outweighing perceived potential benefits. In conclusion, because the risk was often constructed in terms of worries for themselves and others, the framing of health education materials for protective behaviors in these terms may be effective. Furthermore, future COVID-19 vaccine education should address vaccine knowledge and concerns, such as the need for a vaccine and its safety, and emphasize how a vaccination would reduce their chances of severe disease if they were to get sick.

Abstract Background Careful development of interventions using principles of co-production is now recognized as an important step for clinical trial development, but practical guidance on how to do this in practice is lacking. This paper aims (1) provide practical guidance for researchers to co-produce interventions ready for clinical trial by describing the 4-stage process we followed, the challenges experienced and practical tips for researchers wanting to co-produce an intervention for a clinical trial; (2) describe, as an exemplar, the development of our intervention package. Method We used an Integrated Knowledge Translation (IKT) approach to co-produce a telehealth-delivered exercise program for people with stroke. The 4-stage process comprised of (1) a start-up planning phase with the co-production team. (2) Content development with knowledge user informants. (3) Design of an intervention protocol. (4) Protocol refinement. Results and reflections The four stages of intervention development involved an 11-member co-production team and 32 knowledge user informants. Challenges faced included balancing conflicting demands of different knowledge user informant groups, achieving shared power and collaborative decision making, and optimising knowledge user input. Components incorporated into the telehealth-delivered exercise program through working with knowledge user informants included: increased training for intervention therapists; increased options to tailor the intervention to participant’s needs and preferences; and re-naming of the program. Key practical tips include ways to minimise the power differential between researchers and consumers, and ensure adequate preparation of the co-production team. Conclusion Careful planning and a structured process can facilitate co-production of complex interventions ready for clinical trial. Graphical Abstract

Individuals who are immunocompromised (IC) due to therapy or underlying disease are at increased risk of herpes zoster (HZ). This study evaluates the public health impact of recombinant zoster vaccine (RZV) relative to no HZ vaccination for the prevention of HZ among adults aged ≥18 years diagnosed with selected cancers in the United States (US). A static Markov model was used to simulate three cohorts of individuals who are IC with cancer (time horizon of 30 years; one-year cycle length): hematopoietic stem cell transplant (HSCT) recipients, patients with breast cancer (BC; a solid tumor example), and patients with Hodgkin’s lymphoma (HL; a hematological malignancy example). Cohort sizes reflect the estimated annual incidence of each condition in the US population (19,671 HSCT recipients, 279,100 patients with BC, and 8,480 patients with HL). Vaccination with RZV resulted in 2,297; 38,068; and 848 fewer HZ cases for HSCT recipients, patients with BC, and patients with HL, respectively (each versus no vaccine). Vaccination with RZV also resulted in 422; 3,184; and 93 fewer postherpetic neuralgia cases for HSCT, BC, and HL, respectively. Analyses estimated the quality-adjusted life years gained to be 109, 506, and 17 for HSCT, BC, and HL, respectively. To prevent one HZ case, the number needed to vaccinate was 9, 8, and 10, for HSCT, BC, and HL, respectively. These results suggest RZV vaccination may be an effective option to significantly reduce HZ disease burden among patients diagnosed with selected cancers in the US.

Shingrix (Recombinant zoster vaccine, RZV) was approved in October 2017 in the United States (US) for the prevention of herpes zoster in adults aged 50 years and older. The vaccine is administered in two doses, with the second dose administration recommended between two and six months after the first dose. Examination of uptake and series completion is important to ensure appropriate use, especially at the time of vaccine introduction. This report provides demographic characteristics of patients receiving RZV between October 2017 and September 2019, first- and second-dose uptake, and a cumulative estimation of second-dose completion by month for US adults aged 50 years and older. Monthly uptake increased rapidly since October 2017; overall, 7,097,441 first doses of RZV were administered along with 4,277,636 second doses during the observed timeframe. Among people with an observed first-dose administration, 70% and 80% completed the two-dose series within six and 12 months post initial dose, respectively. This evidence suggests that RZV has rapidly been adopted by a large population in the US and most are following manufacturer or policy recommendations regarding series completion. Further analyses are needed to explore potential patient, provider, and policy-relevant characteristics associated with second-dose completion that could serve as targets for further improvement.

Despite tremendous progress in the development of untethered soft robots in recent years, existing systems lack the mobility, model‐based control, and motion planning capabilities of their piecewise rigid counterparts. As in conventional robotic systems, the development of versatile locomotion of soft robots is aided by the integration of hardware design and control with modeling tools that account for their unique mechanics and environmental interactions. Here, a framework for physics‐based modeling, motion planning, and control of a fully untethered swimming soft robot is introduced. This framework enables offline co‐design in the simulation of robot parameters and gaits to produce effective open‐loop behaviors and enables closed‐loop planning over motion primitives for feedback control of a frog‐inspired soft robot testbed. This pipeline uses a discrete elastic rods (DERs) physics engine that discretizes the soft robot as many stretchable and bendable rods. On hardware, an untethered aquatic soft robot that performs frog‐like rowing behaviors is engineered. Hardware validation verifies that the simulation has sufficient accuracy to find the best candidates for sets of parameters offline. The simulator is then used to generate a trajectory library of the robot's motion in simulation that is used in real‐time closed‐loop path following experiments on hardware.

Objective: To investigate the potential public health impact of adult herpes zoster (HZ) vaccination with the adjuvanted recombinant zoster vaccine (RZV) in the United States in the first 15 years after launch. Methods: We used a publicly available model accounting for national population characteristics and HZ epidemiological data, vaccine characteristics from clinical studies, and anticipated vaccine coverage with RZV after launch in 2018. Two scenarios were modeled: a scenario with RZV implemented with 65% coverage after 15 years and a scenario continuing with zoster vaccine live (ZVL) with coverage increasing 10% over the same period. We estimated the numbers vaccinated, and the clinical outcomes and health care use avoided yearly, from January 1, 2018, to December 31, 2032. We varied RZV coverage and investigated the associated impact on HZ cases, complications, and health care resource use. Results: With RZV adoption, the numbers of individuals affected by HZ was predicted to progressively decline with an additional 4.6 million cumulative cases avoided if 65% vaccination with RZV was reached within 15 years. In the year 2032, it was predicted that an additional 1.3 million physicians’ visits and 14.4 thousand hospitalizations could be avoided, compared with continuing with ZVL alone. These numbers could be reached 2 to 5 years earlier with 15% higher RZV vaccination rates. Conclusion: Substantial personal and health care burden can be alleviated when vaccination with RZV is adopted. The predicted numbers of HZ cases, complications, physicians’ visits, and hospitalizations avoided, compared with continued ZVL vaccination, depends upon the RZV vaccination coverage achieved.

Abstract Aim Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea. Methods and results Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO2) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO2 (p = 0.02, p = 0.03). Conclusion Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea.

Abstract. Background:. Acute thrombosis of the superior mesenteric vein (SMV) is a rare but potentially catastrophic condition. Clinically separate from portal venous thrombosis due to a higher proportion of associated thrombophilic disorders and intestinal infarction, SMV thrombosis warrants a distinct approach to management. The aim of this review is to report the evidence for current practice. Methods:. A systematic review was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four clinical trials databases and 4 trial registries were searched. This search was not limited by language or study type, but was limited to an adult population (18 years and above). The search period was between January 1, 2000 and February 28, 2019. The review was registered in the PROSPERO database: CRD42018116825. Bias was assessed using the ROBINS-I tool. Results:. A total of 7989 studies were identified, resulting in 19 observational studies being analyzed. Eighteen studies reported on anti-coagulation, 1 reported on anti-coagulation plus endovascular thrombectomy, 9 reported on thrombolysis, and 10 reported on the role of surgery. Bias assessment showed that confounding was a significant area of potential bias. This review has reported that the management of SMV thrombosis is centered around a patients’ perceived hemodynamic stability. If there is evidence of perforation or peritonism then surgical intervention is advocated. Otherwise, anti-coagulation or thrombolysis is preferred. Conclusions:. The data reported were compared with, and added to, that presented by the European Society for Vascular Surgery 2017 guidelines. Overall the source data were heterogenous, with multiple sources of bias and statistical comparison was not achievable.

This is a case report on a 69-year-old woman who was diagnosed with malignant melanoma presenting in the lung. A complete staging workup was performed by her oncologist, with no skin lesion identified as a primary. CT-guided needle biopsy of the lung nodule was completed, with pathology revealing atypical cells consistent with malignant melanoma. Following full body examination by the cutaneous oncologist, a robotic wedge resection and lymph node dissection accompanied by bronchoscopy were performed. Molecular testing (Caris Life Sciences) of the surgical tumor specimen revealed pathological BRAF DNA mutation in exon 15/p.V600K. The patient was initially treated with nivolumab, then treated with a combination of dabrafenib and trametinib at recurrence.

Abstract 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

Abstract: Hematopoietic cell kinase (HCK) is an SRC family member that is aberrantly upregulated in B-cell neoplasms dependent on MYD88-activating mutations and supports their growth and survival. We showed herein that activation of Toll-like receptor (TLR) signaling in MYD88 wild-type B cells also triggered HCK expression, denoting on path regulatory function for HCK by MYD88. To clarify the signaling cascades responsible for aberrant HCK expression in MYD88-mutated B-cell lymphomas, we performed promoter-binding transcription factor (TF) profiling, PROMO weighted TF consensus binding motif analysis, and chromatin immunoprecipitation studies. We identified PAX5, and the mutated MYD88 downstream signaling mediators STAT3, NF-κB, and AP-1, as important drivers of HCK transcription. Knockdown of PAX5, a crucial regulatory factor required for B-cell commitment and identity, abrogated HCK transcription in MYD88-mutated lymphoma cells. Among AP-1 complex components, JunB showed greatest relevance to TLR/MYD88 signaling and HCK transcription regulation. In MYD88-mutated Waldenström macroglobulinemia and activated B-cell-diffuse large B-cell lymphoma cells, knockdown of MYD88 reduced phosphorylation of JunB but not c-Jun, and knockdown of JunB reduced HCK protein levels. Deletion of STAT3, NF-κB, and AP-1 binding sites reduced corresponding TFs binding and HCK promoter activity. Moreover, inhibitors to STAT3, NF-κB, and AP-1 reduced HCK promoter activity and messenger RNA levels, particularly in combination, in MYD88-mutated lymphoma cells. The findings provide new insights into the transcriptional regulation of HCK prosurvival signaling by mutated MYD88, and the importance of JunB as a downstream mediator of the MYD88-directed signaling apparatus.

Background We previously derived a Universal Vital Assessment (UVA) score to better risk-stratify hospitalized patients in sub-Saharan Africa, including those with infection. Here, we aimed to externally validate the performance of the UVA score using previously collected data from patients hospitalized with acute infection in Rwanda. Methods We performed a secondary analysis of data collected from adults ≥18 years with acute infection admitted to Gitwe District Hospital in Rwanda from 2016 until 2017. We calculated the UVA score from the time of admission and at 72 hours after admission. We also calculated quick sepsis-related organ failure assessment (qSOFA) and modified early warning scores (MEWS). We calculated amalgamated qSOFA scores by inserting UVA cut-offs into the qSOFA score, and modified UVA scores by removing the HIV criterion. The performance of each score determined by the area under the receiver operator characteristic curve (AUC) was the primary outcome measure. Results We included 573 hospitalized adult patients with acute infection of whom 40 (7%) died in-hospital. The admission AUCs (95% confidence interval [CI]) for the prediction of mortality by the scores were: UVA, 0.77 (0.68–0.85); modified UVA, 0.77 (0.68–0.85); qSOFA, 0.66 (0.56–0.75), amalgamated qSOFA, 0.71 (0.61–0.80); and MEWS, 0.74 (0.64, 0.83). The positive predictive values (95% CI) of the scores at commonly used cut-offs were: UVA >4, 0.35 (0.15–0.59); modified UVA >4, 0.35 (0.15–0.59); qSOFA >1, 0.14 (0.07–0.24); amalgamated qSOFA >1, 0.44 (0.20–0.70); and MEWS >5, 0.14 (0.08–0.22). The 72 hour (N = 236) AUC (95% CI) for the prediction of mortality by UVA was 0.59 (0.43–0.74). The Chi-Square test for linear trend did not identify an association between mortality and delta UVA score at 72 hours (p = 0.82). Conclusions The admission UVA score and amalgamated qSOFA score had good predictive ability for mortality in adult patients admitted to hospital with acute infection in Rwanda. The UVA score could be used to assist with triage decisions and clinical interventions, for baseline risk stratification in clinical studies, and in a clinical definition of sepsis in Africa.

BackgroundWe previously derived a Universal Vital Assessment (UVA) score to better risk-stratify hospitalized patients in sub-Saharan Africa, including those with infection. Here, we aimed to externally validate the performance of the UVA score using previously collected data from patients hospitalized with acute infection in Rwanda.MethodsWe performed a secondary analysis of data collected from adults ≥18 years with acute infection admitted to Gitwe District Hospital in Rwanda from 2016 until 2017. We calculated the UVA score from the time of admission and at 72 hours after admission. We also calculated quick sepsis-related organ failure assessment (qSOFA) and modified early warning scores (MEWS). We calculated amalgamated qSOFA scores by inserting UVA cut-offs into the qSOFA score, and modified UVA scores by removing the HIV criterion. The performance of each score determined by the area under the receiver operator characteristic curve (AUC) was the primary outcome measure.ResultsWe included 573 hospitalized adult patients with acute infection of whom 40 (7%) died in-hospital. The admission AUCs (95% confidence interval [CI]) for the prediction of mortality by the scores were: UVA, 0.77 (0.68-0.85); modified UVA, 0.77 (0.68-0.85); qSOFA, 0.66 (0.56-0.75), amalgamated qSOFA, 0.71 (0.61-0.80); and MEWS, 0.74 (0.64, 0.83). The positive predictive values (95% CI) of the scores at commonly used cut-offs were: UVA >4, 0.35 (0.15-0.59); modified UVA >4, 0.35 (0.15-0.59); qSOFA >1, 0.14 (0.07-0.24); amalgamated qSOFA >1, 0.44 (0.20-0.70); and MEWS >5, 0.14 (0.08-0.22). The 72 hour (N = 236) AUC (95% CI) for the prediction of mortality by UVA was 0.59 (0.43-0.74). The Chi-Square test for linear trend did not identify an association between mortality and delta UVA score at 72 hours (p = 0.82).ConclusionsThe admission UVA score and amalgamated qSOFA score had good predictive ability for mortality in adult patients admitted to hospital with acute infection in Rwanda. The UVA score could be used to assist with triage decisions and clinical interventions, for baseline risk stratification in clinical studies, and in a clinical definition of sepsis in Africa.

OBJECTIVES:. To identify the epidemiology and outcome of adults and children with and without sepsis in a rural sub-Sahara African setting. DESIGN:. A priori planned substudy of a prospective, before-and-after trial. SETTING:. Rural, sub-Sahara African hospital. PATIENTS:. One-thousand four-hundred twelve patients (adults, n = 491; children, n = 921) who were admitted to hospital because of an acute infection. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Demographic, clinical, laboratory data, danger signs, and the presence of sepsis (defined as a quick Sequential Organ Failure Assessment score count ≥ 2) at admission were extracted. Sepsis was observed in 69 adults (14.1%) and 248 children (26.9%). Sepsis patients differed from subjects without sepsis in several demographic and clinical aspects. Malaria was the most frequent type of infection in adults (66.7%) and children (63.7%) with sepsis, followed by suspected bacterial and parasitic infections other than malaria. Adults with sepsis more frequently developed respiratory failure (8.7% vs 2.1%; p = 0.01), had a higher in-hospital mortality (17.4% vs 8.3%; p < 0.001), were less often discharged home (81.2% vs 92.2%; p = 0.007), and had higher median (interquartile range) costs of care (30,300 [19,400–49,900] vs 42,500 Rwandan Francs [27,000–64,400 Rwandan Francs]; p = 0.004) than adults without sepsis. Children with sepsis were less frequently discharged home than children without sepsis (93.1% vs 96.4%; p = 0.046). Malaria and respiratory tract infections claimed the highest absolute numbers of lives. The duration of symptoms before hospital admission did not differ between survivors and nonsurvivors in adults (72 [24–168] vs 96 hr [72–168 hr]; p = 0.27) or children (48 [24–72] vs 36 [24–108 hr]; p = 0.8). Respiratory failure and coma were the most common causes of in-hospital death. CONCLUSIONS:. In addition to suspected bacterial, viral, and fungal infections, malaria and other parasitic infections are common and important causes of sepsis in adults and children admitted to a rural hospital in sub-Sahara Africa. The in-hospital mortality associated with sepsis is substantial, primarily in adults.

Purpose: Lafora disease is a genetic neurodegenerative metabolic disorder caused by insoluble polyglucosan aggregate accumulation throughout the central nervous system and body. The retina is an accessible neural tissue, which may offer alternative methods to assess neurological diseases quickly and noninvasively. In this way, noninvasive imaging may provide a means to characterize neurodegenerative disease, which enables earlier identification and diagnosis of disease and the ability to monitor disease progression. In this study, we sought to characterize the retina of individuals with Lafora disease using non-invasive retinal imaging. Methods: One eye of three individuals with genetically confirmed Lafora disease were imaged with optical coherence tomography (OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO). When possible, OCT volume and line scans were acquired to assess total retinal thickness, ganglion cell-inner plexiform layer thickness, and outer nuclear layer + Henle fiber layer thickness. OCT angiography (OCTA) scans were acquired in one subject at the macula and optic nerve head (ONH). AOSLO was used to characterize the photoreceptor mosaic and examine the retinal nerve fiber layer (RNFL). Results: Two subjects with previous seizure activity demonstrated reduced retinal thickness, while one subject with no apparent symptoms had normal retinal thickness. All other clinical measures, as well as parafoveal cone density, were within normal range. Nummular reflectivity at the level of the RNFL was observed using AOSLO in the macula and near the ONH in all three subjects. Conclusions: This multimodal retinal imaging approach allowed us to observe a number of retinal structural features in all three individuals. Most notably, AOSLO revealed nummular reflectivity within the inner retina of each subject. This phenotype has not been reported previously and may represent a characteristic change produced by the neurodegenerative process.

Purpose: To compare foveal hypoplasia and the appearance of the ellipsoid zone (EZ) at the fovea in patients with genetically confirmed achromatopsia (ACHM) and blue cone monochromacy (BCM). Design: Retrospective, multicenter observational study. Participants: Molecularly confirmed patients with ACHM (n = 89) and BCM (n = 33). Methods: We analyzed high-resolution spectral-domain OCT (SD-OCT) images of the macula from patients with BCM. Three observers independently graded SD-OCT images for foveal hypoplasia (i.e., retention of ≥1 inner retinal layers at the fovea), and 4 observers judged the integrity of the EZ at the fovea, based on an established grading scheme. These measures were compared with previously published data from the patients with ACHM. Main Outcome Measures: Presence of foveal hypoplasia and EZ grade. Results: Foveal hypoplasia was significantly more prevalent in ACHM than in BCM (P < 0.001). In addition, we observed a significant difference in the distribution of EZ grades between ACHM and BCM, with grade II EZ being by far the most common phenotype in BCM (61% of patients). In contrast, patients with ACHM had a relatively equal prevalence of EZ grades I, II, and IV. Grade IV EZ was 2.6 times more prevalent in ACHM compared with BCM, whereas grade V EZ (macular atrophy) was present in 3% of both the ACHM and BCM cohorts. Conclusions: The higher incidence of foveal hypoplasia in ACHM than BCM supports a role for cone activity in foveal development. Although there are differences in EZ grades between these conditions, the degree of overlap suggests EZ grade is not sufficient for definitive diagnosis, in contrast to previous reports. Analysis of additional OCT features in similar cohorts may reveal differences with greater diagnostic value. Finally, the extent to which foveal hypoplasia or EZ grade is prognostic for therapeutic potential in either group remains to be seen, but motivates further study.

Background: Atherosclerosis is a systemic inflammatory disease, with common inflammatory processes implicated in both atheroma vulnerability and blood-brain barrier disruption. This prospective multimodal imaging study aimed to measure directly the association between systemic atheroma inflammation (“atheroinflammation”) and downstream chronic cerebral small vessel disease severity.Methods: Twenty-six individuals with ischemic stroke with ipsilateral carotid artery stenosis of >50% underwent 18fluoride-fluorodeoxyglucose-positron emission tomography within 2 weeks of stroke. Small vessel disease severity and white matter hyperintensity volume were assessed using 3-tesla magnetic resonance imaging also within 2 weeks of stroke.Results: Fluorodeoxyglucose uptake was independently associated with more severe small vessel disease (odds ratio 6.18, 95% confidence interval 2.1–18.2, P < 0.01 for the non-culprit carotid artery) and larger white matter hyperintensity volumes (coefficient = 14.33 mL, P < 0.01 for the non-culprit carotid artery).Conclusion: These proof-of-concept results have important implications for our understanding of the neurovascular interface and potential therapeutic exploitation in the management of systemic atherosclerosis, particularly non-stenotic disease previously considered asymptomatic, in order to reduce the burden of chronic cerebrovascular disease.

The Double Asteroid Redirection Test (DART) spacecraft was developed to provide the first measurement for orbital deflection of an asteroid upon intentional impact. The NEXT ion engine is part of the mission, on its maiden voyage. As part of the pre-launch risk reduction, erosion characteristics of the extraction grid system were evaluated using laser measurements of sputtered molybdenum atoms over the envelope of potential throttle conditions for the mission. Erosion rate dependence on propellant flow rate as well as relative density and directionality of molybdenum sputter from grid center to edge were measured. Sputtered atoms were found to have average radial velocity directed toward the engine perimeter and increasing with radial distance. The relative contribution of source and facility background gas and other sources of accelerator grid current was examined as well as the influence of several engine operating parameters. Facility background gas was found to influence engine operation more than a wall-mounted pressure gauge and typical assumptions about ingestion would indicate. Far-field flux was estimated over the full angular range based on the near-field relative density and velocity results and relying on quartz crystal microbalance data at one location to fix absolute numbers everywhere. The results substantially deepen knowledge and understanding of the complex grid erosion process of the engine and its lifetime, as grid failure via erosion is the normal life limiter. Study results are also relevant to thruster–spacecraft integration issues such as molybdenum deposition rate on solar cells and other spacecraft surfaces.

As demand for commodities increases globally, resource-rich countries are focal areas for industrial expansion. The extractives sector is driving unprecedented growth of infrastructure (e.g., roads, railways and pipelines) into sparsely populated regions, which contain some of the world’s remaining intact forests. Yet, the extent of the threat posed by an increased footprint of extractive industries is not well understood. Here we provide a novel global assessment of the potential threat posed to tropical Intact Forest Landscapes (IFLs), continuous patches of forest that have no remotely sensed signs of human activity or forest fragmentation, from the extractives sector including mining, oil and gas projects, using one of the most extensive global spatial datasets on extractives concessions to date. We found ∼20% of the global tropical IFL estate is designated as extractive’s concessions, presenting an enormous threat to these forests. Oil and gas concessions overlap with 408,000 km2 of tropical IFLs (7.85% of total IFL area), with the biggest overlap in the Democratic Republic of the Congo and Papua New Guinea. Mining concessions overlap with 589,000 km2 (11.33%) of tropical IFL area, mainly in Brazil and Democratic Republic of Congo. As the majority of concessions overlapping IFLs are currently at the exploration stages for all types of extractives, now is the time to plan for reducing the potential threat through strategies such as identifying “no go” areas and applying the mitigation hierarchy. Nations and investors should undertake regional strategic environmental assessments to reduce impacts, including potential indirect and cumulative impacts of multiple projects and other threats in the landscape. We also call for banks that funders of extractives projects to apply global best practice industry environmental safeguards that recognize the value of intact forests and the risk of cumulative impacts to these unique sites.

Ibrutinib is highly active and produces long-term responses in patients with Waldenström macroglobulinemia (WM), but acquired resistance can occur with prolonged treatment. We therefore evaluated the natural history and treatment outcomes in 51 WM patients with acquired resistance to ibrutinib monotherapy. The median time between ibrutinib initiation and discontinuation was 2 years (range, 0.4-6.5 years). Following discontinuation of ibrutinib, a rapid increase in serum immunoglobulin M level was observed in 60% (29/48) of evaluable patients, of whom ten acutely developed symptomatic hyperviscosity. Forty-eight patients (94%) received salvage therapy after ibrutinib. The median time to salvage therapy after ibrutinib cessation was 18 days (95% confidence interval [CI]: 13-27). The overall and major response rates to salvage therapy were 56% and 44%, respectively, and the median duration of response was 48 months (95% CI: 34-not reached). Quadruple-class (rituximab, alkylator, proteasome inhibitor, ibrutinib) exposed disease (odds ratio [OR] 0.20, 95% CI: 0.05-0.73) and salvage therapy ≤7 days after discontinuing ibrutinib (OR 4.12, 95% CI: 1.07- 18.9) were identified as independent predictors of a response to salvage therapy. The 5-year overall survival (OS) following discontinuation of ibrutinib was 44% (95% CI: 26-75). Response to salvage therapy was associated with better OS after ibrutinib (hazard ratio 0.08, 95% CI: 0.02-0.38). TP53 mutations were associated with shorter OS, while acquired BTK C481S mutations had no impact. Our findings reveal that continuation of ibrutinib until subsequent treatment is associated with improved disease control and clinical outcomes.

Zoster Vaccine Live (ZVL) is marketed in the US since 2008, and a non-live adjuvanted Recombinant Zoster Vaccine (RZV) was approved in 2017. Literature suggests that waning of ZVL efficacy may necessitate additional vaccination. The Advisory Committee on Immunization Practices recommended vaccination with RZV in immunocompetent adults aged 50+ years old, including those previously vaccinated with ZVL. The objective of this study was to determine the cost-effectiveness of vaccinating US adults aged 60+ years old, previously vaccinated with ZVL. The ZOster ecoNomic Analysis (ZONA) model, a deterministic Markov model, was adapted to follow a hypothetical 1 million(M)-person cohort of US adults previously vaccinated with ZVL. Model inputs included demographics, epidemiology, vaccine characteristics, utilities and costs. Costs and quality-adjusted life-years (QALYs) were presented over the lifetimes of the cohort from the year of additional vaccination, discounted 3% annually. The model estimated that, vaccination with RZV 5 years after previous vaccination with ZVL, would reduce disease burden compared with no additional vaccination, resulting in a gain of 1,633 QALYs at a total societal cost of $96M (incremental cost-effectiveness ratio: $58,793/QALY saved). Compared with revaccinating with ZVL, vaccination with RZV would result in a gain of 1,187 QALYs and societal cost savings of almost $84M. Sensitivity, scenario, and threshold analyses demonstrated robustness of these findings. Vaccination with RZV is predicted to be cost-effective relative to no additional vaccination, assuming a threshold of $100,000/QALY, and cost-saving relative to ZVL revaccination of US adults aged 60+ years old who have been previously vaccinated with ZVL.

Objectives: This study aimed to explore the attitudes of Omani nurses towards evidence-based practice (EBP) and their perceptions of the barriers to and facilitators of EBP implementation in Oman. In addition, the attitudes and perceptions of nurse leaders and staff nurses were compared. Methods: This descriptive cross-sectional study was conducted between August and October 2016 in three suburban governmental hospitals in Northern Oman. A demographic questionnaire and two EBP instruments were used to collect data from 282 registered Omani nurses, including the Evidence-Based Nursing Attitude Questionnaire and the Developing Evidence-Based Practice Questionnaire. Results: A total of 260 Omani nurses took part in the study (response rate: 92.2%). On the whole, the nurses had positive attitudes towards EBP, with no significant difference in mean attitude scores per item between staff nurses and nurse leaders (3.98 ± 0.46 versus 4.03 ± 0.50; P = 0.431). However, in comparison to staff nurses, nurse leaders had higher scores per item for the barriers to changing practice and finding and reviewing evidence subsections, with lower scores for the facilitators to changing practice section. Conclusion: In accordance with the international literature, Omani nurses had positive attitudes towards EBP as well as similar perceptions of barriers and facilitators to EBP implementation. These findings may help to inform recommendations for the integration of EBP in educational programmes and clinical settings in Oman, as well as to facilitate necessary changes in nursing practice. Keywords: Evidence-Based Practice; Nurses; Attitudes; Perceptions; Oman.

Hepatitis A and B disease burden persists in the US. We assessed hepatitis A and hepatitis B vaccination series completion rates among 350,240 commercial/Medicare and 12,599 Medicaid enrollees aged ≥19 years. A vaccination series was considered as completed provided that the minimum interval between doses, as defined by the CDC, and the minimum number of doses were reached. We stratified completion rates by vaccine type (i.e. monovalent or bivalent) at initial vaccination for each cohort. In the commercial/Medicare cohort, the series completion rate was 32.0% for hepatitis A and 39.6% for hepatitis B among those who initiated with a monovalent vaccine, and it was 36.2% for hepatitis A and 48.9% for hepatitis B among those who initiated with a bivalent vaccine. In the Medicaid cohort, the series completion rate was 21.0% for hepatitis A and 24.0% for hepatitis B among those who initiated with a monovalent vaccine, and it was 19.0% for hepatitis A and 24.6% for hepatitis B among those who initiated with a bivalent vaccine. In conclusion, hepatitis A and B vaccination series completion rates were low, and appeared to be lower among Medicaid than among commercial/Medicare enrollees. Commercial/Medicare enrollees who initiated with a bivalent vaccine had higher series completion rates than those who initiated with monovalent vaccines – an observation that was not made among Medicaid enrollees.

Decades of reductionist approaches in biology have achieved spectacular progress, but the proliferation of subdisciplines, each with its own technical and social practices regarding data, impedes the growth of the multidisciplinary and interdisciplinary approaches now needed to address pressing societal challenges. Data integration is key to a reintegrated biology able to address global issues such as climate change, biodiversity loss, and sustainable ecosystem management. We identify major challenges to data integration and present a vision for a "Data as a Service"-oriented architecture to promote reuse of data for discovery. The proposed architecture includes standards development, new tools and services, and strategies for career-development and sustainability.

Abstract. Ibrutinib is the first approved therapy for symptomatic patients with Waldenström macroglobulinemia (WM). The approval was based on a single, multicenter, phase II trial in previously treated WM patients. We sought to evaluate whether there were differences in clinical characteristics, response, and survival outcomes to ibrutinib monotherapy between WM patients treated on and off clinical trials. Treatment naïve and previously treated patients who received ibrutinib monotherapy at our institution and participated in two prospective studies (ON trial; n = 72) or a prospective database (OFF trial; n = 157) were included. The median times from WM diagnosis to ibrutinib initiation were 3.1 and 3.5 years for ON and OFF trial patients, respectively (p = 0.38). Similar rates of categorical response at 6, 12, and 24 months and at best response were also observed between ON trial and OFF trial patients. The 4-year PFS and OS rates for ON trial and OFF trial patients were 72% and 63%, respectively (log-rank p = 0.14) and 83% and 81%, respectively (log-rank p = 0.14). CXCR4 mutations impacted response and survival outcomes to ibrutinib monotherapy. The 4-year rates of ibrutinib discontinuation in ON and OFF trial patients were 36% and 44%, respectively (p = 0.11). Ibrutinib is effective in the routine clinical care of both treatment-naïve and previously treated WM patients. The findings of our study validate the efficacy of ibrutinib monotherapy reported in multiple phase II clinical trials.

OBJECTIVE:To assess the value of the inability to walk unassisted to predict hospital mortality in patients with suspected infection in a resource-limited setting. METHODS:This is a post hoc study of a prospective trial performed in rural Rwanda. Patients hospitalized because of a suspected acute infection and who were able to walk unassisted before this disease episode were included. At hospital presentation, the walking status was graded into: 1) can walk unassisted, 2) can walk assisted only, 3) cannot walk. Receiver operating characteristic (ROC) analyses and two-by-two tables were used to determine the sensitivity, specificity, negative and positive predictive values of the inability to walk unassisted to predict in-hospital death. RESULTS:One-thousand-sixty-nine patients were included. Two-hundred-one (18.8%), 315 (29.5%), and 553 (51.7%) subjects could walk unassisted, walk assisted or not walk, respectively. Their hospital mortality was 0%, 3.8% and 6.3%, respectively. The inability to walk unassisted had a low specificity (20%) but was 100% sensitive (CI95%, 90-100%) to predict in-hospital death (p = 0.00007). The value of the inability to walk unassisted to predict in-hospital mortality (AUC ROC, 0.636; CI95%, 0.564-0.707) was comparable to that of the qSOFA score (AUC ROC, 0.622; CI95% 0.524-0.728). Fifteen (7.5%), 34 (10.8%) and 167 (30.2%) patients who could walk unassisted, walk assisted or not walk presented with a qSOFA score count ≥2 points, respectively (p

Individuals vary in their potential to acquire and transmit infections, but this fact is currently underexploited in disease control strategies. We trialled a trait-based vaccination strategy to reduce tuberculosis in free-living meerkats by targeting high-contact meerkats (socially dominant individuals) in one study arm, and high-susceptibility individuals (young subordinates) in a second arm. We monitored infection within vaccinated groups over two years comparing the results with untreated control groups. Being a member of a high-contact group had a protective effect on individuals’ survival times (Hazard Ratio = 0.5, 95% Confidence Interval, CI: 0.29–0.88, p = 0.02) compared to control groups. Over the study, odds of testing positive for tuberculosis increased more than five-fold in control groups (Odds Ratio = 5.40, 95% CI = 0.94–30.98, p = 0.058); however, no increases were observed in either of the treatment arms. Targeted disease control approaches, such as the one described in this study, allow for reduced numbers of interventions. Here, trait-based vaccination was associated with reduced infection rates and thus has the potential to offer more efficient alternatives to traditional mass-vaccination policies. Such improvements in efficiency warrant further study and could make infectious disease control more practically achievable in both animal (particularly wildlife) and human populations.

Abstract Background Heart failure (HF) is a major cardiovascular disease with increasing prevalence. Thiamine deficiency occurs in 33% of patients with HF. However, the effectiveness of thiamine supplementation in HF is not known. Methods In a placebo-controlled randomized two-period crossover feasibility trial, patients age ≥ 60 years with HF and reduced ejection fraction (HFrEF, EF ≤ 45%) will be randomized to thiamine 500 mg oral capsule once daily or placebo for 3 months, then crossed over to the other intervention after a 6-week washout period. The primary outcome is recruitment rate. Secondary outcomes include feasibility and clinical measures. Feasibility outcomes include refusal rate, retention rate, and compliance rate. Secondary clinical outcomes include left ventricular ejection fraction, peak global longitudinal strain measured by echocardiography, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) quality of life score, and clinical outcomes (all-cause mortality, HF hospitalizations, and HF emergency room visits). Discussion Thiamine is potentially a safe and low-cost treatment for older patients with HFrEF. Results from this study will inform the feasibility of a large clinical trial with clinical endpoints. The findings will be published in a peer review journal and presented at a relevant conference. This study has received full approval from the Hamilton Integrated Research Ethics Board (18-4537) and Health Canada (210603). This trial is funded by the Hamilton Health Sciences New Investigator Grant (15-387) and the McMaster/St. Peter’s Hospital Chair of Aging. Trial registration NCT03228030 (ClinicalTrials.gov), registered July 24, 2017.

Research has established that sexual minority young adults generally report fewer desires and fewer expectations for parenthood than do their heterosexual peers. Little is known, however, about other desires and expectations. Is parenthood the only domain in which lesbian and gay individuals report fewer desires and expectations than their heterosexual peers? Or do lower aspirations among lesbian and gay adults about parenthood also occur in other domains, such as marriage and work? In this study, we explored a variety of desires and expectations for the future among lesbian, gay, and heterosexual young adults. Participants for this internet survey were recruited via social media, and included 368 childless cisgender young adults (211 lesbian or gay and 157 heterosexual) living in the United States. There were three main findings. First, while lesbian/gay individuals were less likely than heterosexual participants to express desire for parenthood, desires in the other future domains did not vary across sexual orientation. Lesbian/gay participants were as likely as heterosexual individuals to desire marriage, friendships, and community connections, as well as career and economic success. Results for expectations were, however, very different. Lesbian/gay participants were less likely than heterosexual individuals to expect that they would marry, become parents, feel connected to a community, achieve meaningful careers, live in their ideal housing, or that they would attain financial stability. Thus, although desires were largely unrelated to sexual orientation, many expectations were strongly linked to it. Lesbian and gay individuals were also far more likely than their heterosexual peers to desire future goals that they did not expect to achieve. Overall, for lesbian/gay young adults, low parenthood aspirations were part of a general pattern of low expectations (though not reduced desires) across a number of life domains.

Diagnostic tests are used to classify individual animals’ infection statuses. However, validating test performance in wild animals without gold standard tests is extremely challenging, and the issue is further complicated in chronic conditions where measured immune parameters vary over time. Here, we demonstrate the value of combining evidence from different diagnostic approaches to aid interpretation in the absence of gold standards, large sample sizes, and controlled environments. Over a two-year period, we sampled 268 free-living meerkats (Suricata suricatta) longitudinally for Mycobacterium suricattae (a causative agent of tuberculosis), using three ante-mortem diagnostic tests based on mycobacterial culture, and antigen-specific humoral and cell-mediated immune responses, interpreting results both independently and in combination. Post-mortem cultures confirmed M. suricattae infection in 22 animals, which had prior ante-mortem information, 59% (13/22) of which were test-positive on a parallel test interpretation (PTI) of the three ante-mortem diagnostic assays (95% confidence interval: 37–79%). A similar ability to detect infection, 65.7% (95% credible interval: 42.7–84.7%), was estimated using a Bayesian approach to examine PTI. Strong evidence was found for a near doubling of the hazard of death (Hazard Ratio 1.75, CI: 1.14–2.67, p = 0.01), associated with a positive PTI result, thus demonstrating that these test results are related to disease outcomes. For individual tests, small sample sizes led to wide confidence intervals, but replication of conclusions, using different methods, increased our confidence in these results. This study demonstrates that combining multiple methodologies to evaluate diagnostic tests in free-ranging wildlife populations can be a useful approach for exploiting such valuable datasets.

Healthcare costs are lower for adults who consume more vegetables; however, the association between healthcare costs and fruit and vegetable varieties is unclear. Our aim was to investigate the association between (i) baseline fruit and vegetable (F&V) varieties, and (ii) changes in F&V varieties over time with 15-year healthcare costs in an Australian Longitudinal Study on Women’s Health. The data for Survey 3 (n = 8833 women, aged 50–55 years) and Survey 7 (n = 6955, aged 62–67 years) of the 1946–1951 cohort were used. The F&V variety was assessed using the Fruit and Vegetable Variety (FAVVA) index calculated from the Cancer Council of Victoria’s Dietary Questionnaire for Epidemiological Studies food frequency questionnaire. The baseline FAVVA and change in FAVVA were analysed as continuous predictors of Medicare claims/costs by using multiple regression analyses. Healthy weight women made, on average, 4.3 (95% confidence interval (CI) 1.7–6.8) fewer claims for every 10-point-higher FAVVA. Healthy weight women with higher fruit varieties incurred fewer charges; however, this was reversed for women overweight/obese. Across the sample, for every 10-point increase in FAVVA over time, women made 4.3 (95% CI 1.9–6.8) fewer claims and incurred $309.1 (95% CI $129.3–488.8) less in charges over 15 years. A higher F&V variety is associated with a small reduction in healthcare claims for healthy weight women only. An increasing F&V variety over time is associated with lower healthcare costs.

Abstract Background Scientific names in biology act as universal links. They allow us to cross-reference information about organisms globally. However variations in spelling of scientific names greatly diminish their ability to interconnect data. Such variations may include abbreviations, annotations, misspellings, etc. Authorship is a part of a scientific name and may also differ significantly. To match all possible variations of a name we need to divide them into their elements and classify each element according to its role. We refer to this as ‘parsing’ the name. Parsing categorizes name’s elements into those that are stable and those that are prone to change. Names are matched first by combining them according to their stable elements. Matches are then refined by examining their varying elements. This two stage process dramatically improves the number and quality of matches. It is especially useful for the automatic data exchange within the context of “Big Data” in biology. Results We introduce Global Names Parser (gnparser). It is a Java tool written in Scala language (a language for Java Virtual Machine) to parse scientific names. It is based on a Parsing Expression Grammar. The parser can be applied to scientific names of any complexity. It assigns a semantic meaning (such as genus name, species epithet, rank, year of publication, authorship, annotations, etc.) to all elements of a name. It is able to work with nested structures as in the names of hybrids. gnparser performs with ≈99% accuracy and processes 30 million name-strings/hour per CPU thread. The gnparser library is compatible with Scala, Java, R, Jython, and JRuby. The parser can be used as a command line application, as a socket server, a web-app or as a RESTful HTTP-service. It is released under an Open source MIT license. Conclusions Global Names Parser (gnparser) is a fast, high precision tool for biodiversity informaticians and biologists working with large numbers of scientific names. It can replace expensive and error-prone manual parsing and standardization of scientific names in many situations, and can quickly enhance the interoperability of distributed biological information.