A gero-informatics tool to enhance the care of hospitalized older adults with cognitive impairment

Approximately 50% of hospitalized elders have cognitive impairment (CI) that increases their vulnerability to hospital-acquired complications. Matching geriatric evaluation and recommendations to the true pace of hospital care may improve the care of elders in general, in particular those with CI. Integrating information technology into geriatric services (gero-informatics) might allow reduction of the time to implementation of geriatric recommendations and prevent the initiation of potentially harmful medications and procedures during the critical first 48 hours of hospitalization. This paper reviews our local gero-informatics early experience of developing a computerized decision support system (CDSS) to enhance hospital care for elders with CI by reducing inappropriate use of anticholinergic medications, urinary catheters, and physical restraints

Selecting a change and evaluating its impact on the performance of a complex adaptive health care delivery system

Complexity science suggests that our current health care delivery system acts as a complex adaptive system (CAS). Such systems represent a dynamic and flexible network of individuals who can coevolve with their ever changing environment. The CAS performance fluctuates and its members’ interactions continuously change over time in response to the stress generated by its surrounding environment. This paper will review the challenges of intervening and introducing a planned change into a complex adaptive health care delivery system. We explore the role of the “reflective adaptive process” in developing delivery interventions and suggest different evaluation methodologies to study the impact of such interventions on the performance of the entire system. We finally describe the implementation of a new program, the Aging Brain Care Medical Home as a case study of our proposed evaluation process

The integrin αvβ8 mediates epithelial homeostasis through MT1-MMP–dependent activation of TGF-β1

Întegrins, matrix metalloproteases (MMPs), and the cytokine TGF-β have each been implicated in homeostatic cell behaviors such as cell growth and matrix remodeling. TGF-β exists mainly in a latent state, and a major point of homeostatic control is the activation of TGF-β. Because the latent domain of TGF-β1 possesses an integrin binding motif (RGD), integrins have the potential to sequester latent TGF-β (SLC) to the cell surface where TGF-β activation could be locally controlled. Here, we show that SLC binds to αvβ8, an integrin expressed by normal epithelial and neuronal cells in vivo. This binding results in the membrane type 1 (MT1)-MMP–dependent release of active TGF-β, which leads to autocrine and paracrine effects on cell growth and matrix production. These data elucidate a novel mechanism of cellular homeostasis achieved through the coordination of the activities of members of three major gene families involved in cell–matrix interactions

Comorbidity Profile and Health Care Utilization in Elderly Patients with Serious Mental Illnesses

Objectives Patients with serious mental illness are living longer. Yet there remain few studies that focus on health care utilization and its relationship to comorbidities in these elderly mentally ill patients. Design Comparative study. Information on demographics, comorbidities and health care utilization were taken from an electronic medical record system. Setting Wishard Health Services senior care and community mental health clinics. Participants Patients age 65 years and over-255 patients with serious mental illness (schizophrenia, major recurrent depression and bipolar illness) attending a mental health clinic and a representative sample of 533 non-demented patients without serious mental illness attending primary care clinics. Results Patients having serious mental illness had significantly higher rates of medical emergency room visits (p=0.0027) and significantly longer lengths of medical hospitalizations (p<0.0001) than did the primary care control group. The frequency of medical comorbidities such as diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, thyroid disease, and cancer were not significantly different between the groups. Hypertension was lower in the mentally ill group (p<0.0001). Reported falls (p<0.0001), diagnoses of substance abuse (p=0.02), and alcoholism (p=0.0016) were higher in the seriously mentally ill. The differences in health care utilization between the groups remained significant after adjusting for comorbidity levels, lifestyle factors, and attending primary care. Conclusions Our findings of higher rates of emergency care, longer hospitalizations, and increased frequency of falls, substance abuse, and alcoholism suggest the elderly seriously mentally ill remain a vulnerable population requiring an integrated model of health care

Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D, mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse. We here present the protocol of an interventional clinical phase II study to test the hypothesis, that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects.</p> <p>Methods/Design</p> <p>The EVIDIMS trial is a German multi-center, stratified, randomized, controlled and double-blind clinical phase II pilot study. Eighty patients with the diagnosis of definite multiple sclerosis or clinically isolated syndrome who are on a stable immunomodulatory treatment with interferon-β1b will be randomized to additionally receive either high-dose (average daily dose 10.200 IU) or low-dose (average daily dose 200 IU) cholecalciferol for a total period of 18 months. The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla. Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration, clinical parameters for disease activity, as well as cognition, fatigue, depression, and quality of life. Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters.</p> <p>Discussion</p> <p>In light of the discrepancy between existing epidemiological and preclinical data on the one hand and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients. The study design presented here fulfills the criteria of a high-quality clinical phase II trial in MS.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01440062">NCT01440062</a></p

Seasonal fluxes of carbonyl sulfide in a midlatitude forest

Carbonyl sulfide (OCS), the most abundant sulfur gas in the atmosphere, has a summer minimum associated with uptake by vegetation and soils, closely correlated with CO2. We report the first direct measurements to our knowledge of the ecosystem flux of OCS throughout an annual cycle, at a mixed temperate forest. The forest took up OCS during most of the growing season with an overall uptake of 1.36 ± 0.01 mol OCS per ha (43.5 ± 0.5 g S per ha, 95% confidence intervals) for the year. Daytime fluxes accounted for 72% of total uptake. Both soils and incompletely closed stomata in the canopy contributed to nighttime fluxes. Unexpected net OCS emission occurred during the warmest weeks in summer. Many requirements necessary to use fluxes of OCS as a simple estimate of photosynthesis were not met because OCS fluxes did not have a constant relationship with photosynthesis throughout an entire day or over the entire year. However, OCS fluxes provide a direct measure of ecosystem-scale stomatal conductance and mesophyll function, without relying on measures of soil evaporation or leaf temperature, and reveal previously unseen heterogeneity of forest canopy processes. Observations of OCS flux provide powerful, independent means to test and refine land surface and carbon cycle models at the ecosystem scale.Engineering and Applied Science

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Farming, foreign holidays, and vitamin D in Orkney

Orkney, north of mainland Scotland, has the world's highest prevalence of multiple sclerosis (MS); vitamin D deficiency, a marker of low UV exposure, is also common in Scotland. Strong associations have been identified between vitamin D deficiency and MS, and between UV exposure and MS independent of vitamin D, although causal relationships remain to be confirmed. We aimed to compare plasma 25-hydroxyvitamin D levels in Orkney and mainland Scotland, and establish the determinants of vitamin D status in Orkney. We compared mean vitamin D and prevalence of deficiency in cross-sectional study data from participants in the Orkney Complex Disease Study (ORCADES) and controls in the Scottish Colorectal Cancer Study (SOCCS). We used multivariable regression to identify factors associated with vitamin D levels in Orkney. Mean (standard deviation) vitamin D was significantly higher among ORCADES than SOCCS participants (35.3 (18.0) and 31.7 (21.2), respectively). Prevalence of severe vitamin D deficiency was lower in ORCADES than SOCCS participants (6.6% to 16.2% p = 1.1 x 10(-15)). Older age, farming occupations and foreign holidays were significantly associated with higher vitamin D in Orkney. Although mean vitamin D levels are higher in Orkney than mainland Scotland, this masks variation within the Orkney population which may influence MS risk

Virology under the microscope—a call for rational discourse

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we – a broad group of working virologists – seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century