The WorkingWell Smartphone App for Individuals with Serious Mental Illnesses: A Proof-of-Concept, Mixed Methods Feasibility Study (Preprint)

Background: The disparities in employment for individuals with serious mental illnesses (SMI) have been well documented, as have the benefits of work. The benefits of mobile technology in providing accessible, in-the-moment support for these individuals has been demonstrated. The WorkingWell mobile app was developed to meet the need for accessible follow-along supports for individuals with SMI in the workplace. Objective: We explore the usability, usage, usefulness and overall feasibility of the WorkingWell mobile app with individuals with SMI receiving community-based services and actively employed. Methods: In this proof-of-concept, mixed methods, two-month feasibility study (N=40), employed individuals with SMI were recruited in mental health agencies. Participants completed surveys regarding background characteristics and cellphone use at enrollment; and responded to interview items regarding app usability, usage and usefulness in technical assistance calls at one, two, four and six weeks of study participation and in the exit interview at 8 weeks. Data on the frequency of app usage were downloaded and monitored on a daily basis. A version of the System Usability Scale (SUS) was administered in the exit interview. Feasibility was determined by the percent of users completing the study. General impressions were obtained from users regarding user support materials, technical assistance, and study procedures. Results: Over half of the participants were male (60%, 24/40). The majority were age 55 or under (70%, 28/40), Caucasian (80%, 32/40), had less than a 4-year college education (78%, 31/40), were employed part-time (98%, 39/40), had been working more than six months (60%, 24/40), and indicated a diagnosis of bipolar, schizoaffective or depressive disorder (84%, 16/25). The vast majority of participants owned cellphones (95%, 38/40), using them multiple times per day (83%, 33/40). Their average rating on SUS usability items was 3.93 (SD = 0.77; range = 1.57 to 5.00), reflecting positive responses. Participants, in general, indicated WorkingWell was “very easy”, “straightforward”, “simple”, and “user-friendly”. Usability challenges were related to personal issues (e.g., memory) or to difficulties with the phone or app. Data on app usage varied considerably. The most frequent navigations were to the home screen, followed by Rate My Day and My Progress, and then by Manage the Moment and Remind Me. The app was described as useful by most study participants; 86% (30/35) agreed the app would help them manage better on the job. Thirty-five of the 40 original participants (87%) completed the study. Conclusions: The WorkingWell app is a feasible approach to providing accessible, as-needed employment support for individuals with SMI. The app would benefit from additional modifications to address recommendations from feasibility testing. Controlled research with larger samples, more diverse in individual characteristics and workplace settings, is essential to demonstrating the effectiveness of the app

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders

Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD

Hanford Site National Environmental Policy Act (NEPA) Characterization

This document describes the U.S. Department of Energy’s (DOE) Hanford Site environment. It is intended to provide a consistent description of the Hanford Site for the many environmental documents being prepared by DOE contractors concerning the National Environmental Policy Act (NEPA). No statements regarding significance or environmental consequences are provided. This year’s report is the eighteen revision of the original document published in 1988 and is (until replaced by the nineteenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. Two chapters are included in this document (Chapters 4 and 6), numbered to correspond to chapters typically presented in environmental impact statements (EISs) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology; air quality; geology; hydrology; ecology; cultural, archaeological, and historical resources; socioeconomics; noise; and occupational health and safety. Sources for extensive tabular data related to these topics are provided in the chapter. When possible, subjects are divided into a general description of the characteristics of the Hanford Site, followed by site-specific information, where available, for the 100, 200, 300 and other areas. This division allows the reader to go directly to those sections of particular interest. When specific information on each of these separate areas is not complete or available, the general Hanford Site description should be used. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to NEPA documents prepared for Hanford Site activities. Information in Chapter 6 can be adapted and supplemented with specific information covering statutory and regulatory requirements for use in an environmental assessment or environmental impact statement. When preparing environmental assessments and EISs, authors should consult Recommendations for the Preparation of Environmental Assessments and Environmental Impact Statements published by the DOE Office of NEPA Oversight (DOE 2004). Additional direction and guidance on the preparation of DOE NEPA documents can be found at http://tis.eh.doe.gov/nepa/guidance.html. Individuals seeking baseline data on the Hanford Site and its past activities may also use the information contained in this document to evaluate projected activities and their impacts. Pacific Northwest National Laboratory (PNNL) staff prepared individual sections of this document, with input from other Hanford Site contractors with the best available information through May 2007. More detailed data are available from reference sources cited or from the authors. For this 2007 revision, the following sections of the document were reviewed by the authors and updated with the best available information through May 2005: Climate and Meteorology Air Quality Geology – Seismicity section only Hydrology – Flow charts for the Columbia and Yakima rivers only Ecology – Threatened and Endangered Species subsection only Socioeconomics Occupational Safety All of Chapter 6

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Lancet

BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation

Implementing baseline ecological and human health field assessments in the Revitalizing Informal Settlements and their Environments (RISE) programme in Makassar, Indonesia: an interdisciplinary study

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420Background The Revitalizing Informal Settlements and their Environments (RISE) programme aims to assess the health, wellbeing, and ecological impacts of a water-sensitive-cities approach to improving urban informal settlements. Incorporating water-cycle management and green technology sanitation strategies, we aim to reduce flood risk and improve sanitation and waste water treatment leading to cleaner and healthier environments. Here we present the initial design pre-intervention for evaluation in the first 12 settlements in Makassar, Indonesia. Methods Initial environmental, and wellbeing and human health assessments were implemented starting in October, 2018, in 12 settlements in Makassar, Indonesia. Ecological assessments include measuring of temperature and humidity via iButtons installed in select homes, recording of bio-acoustic to measure biodiversity within settlement boundaries, and trapping disease vectors quarterly. Implemented evaluation of environmental contamination includes sampling water and soil sources for total coliforms as well as collecting soil via bootsocks by walking predefined transects. Human assessment includes an annual baseline survey of all settlement households, assessing self-reported symptoms, health-care system utilisation, and subjective wellbeing. Additionally, children younger than 5 years are surveyed quarterly for caregiver reported symptoms of diarrhoea and febrile illness, blood samples and anthropometry are being collected annually, and faeces samples are requested quarterly. Findings Ecological assessments have provided more than a million temperature data points. 21 000 mosquitos have been captured and identified. A total of 114 water samples, 84 bootsocks, and 91 soil samples have been collected, with sampling prior to and during the wet season. We have identified over 600 households within the 12 settlements. Health assessments of children under the age of 5 years have revealed 282 children with collection of 234 faeces samples and 188 blood samples. Interpretation We have successfully implemented baseline ecological and human health and wellbeing assessment tools in all 12 settlements, which will allow for the evaluation of water-sensitive-cities approach in RISE programme.https://doi.org/10.1016/S2542-5196(19)30151-23Suppl

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment