Aggregated Antibiograms and Monitoring of Drug-Resistant Streptococcus pneumoniae

Community-specific antimicrobial susceptibility data may help monitor trends among drug-resistant Streptococcus pneumoniae and guide empiric therapy. Because active, population-based surveillance for invasive pneumococcal disease is accurate but resource intensive, we compared the proportion of penicillin-nonsusceptible isolates obtained from existing antibiograms, a less expensive system, to that obtained from 1 year of active surveillance for Georgia, Tennessee, California, Minnesota, Oregon, Maryland, Connecticut, and New York. For all sites, proportions of penicillin-nonsusceptible isolates from antibiograms were within 10 percentage points (median 3.65) of those from invasive-only isolates obtained through active surveillance. Only 23% of antibiograms distinguished between isolates intermediate and resistant to penicillin; 63% and 57% included susceptibility results for erythromycin and extended-spectrum cephalosporins, respectively. Aggregating existing hospital antibiograms is a simple and relatively accurate way to estimate local prevalence of penicillin-nonsusceptible pneumococcus; however, antibiograms offer limited data on isolates with intermediate and high-level penicillin resistance and isolates resistant to other agents

Maintain Your Brain: outcomes of an online program to prevent cognitive decline with aging.

Background Efforts to prevent cognitive decline with aging have had mixed results with successful interventions delivered in person. While online approaches are more scalable and feasible to deliver at a population level, no multimodal online intervention has yet been demonstrated efficacy. We aimed to reduce cognitive decline with ageing using an online package of interventions delivered intensively for 12 months followed by monthly boosters for 24 months. Method Invitations were sent to people aged 55‐77 years from the 45 and Up study, a population‐based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n = 267,000). Participants were required to be eligible for at least two of four modules addressing physical inactivity and associated health risks (Physical Activity), adherence to a Mediterranean‐type diet and health risks associated with poor nutrition (Nutrition), cognitive activity (Brain Training) and mental well‐being (Peace of Mind). Participants received modules based on their risks, with 1:1 randomized allocation to active personalised coaching modules (intervention) or static information‐based modules (control). The primary outcome was change in an online combined multi‐domain cognitive score measured using COGSTATE and Cambridge Brain Sciences tests. Secondary outcomes included specific cognitive domain and ANU‐ADRI risk scores. Result Of 96,418 invitations issued, 14,064 (14%) consented, 11,026 (11%) were eligible and 6,104 (6%) completed all baseline assessments. Over three years, using intention to treat analysis, the intervention group improved significantly more in the global composite cognition (p<0.001). Significant benefits were also found in complex attention, executive function and learning and memory (all p<0.001), as well as on a validated dementia risk instrument (p = 0.007). Results were similar when adjusted for baseline age, gender, dementia risk and number of modules eligible and when analysis was based on those completing follow‐up. Conclusion An online platform tailored to individuals’ risk factor profiles over three years significantly delayed cognitive decline in older adults. This platform is scalable; if delivered at a population level with may help reduce the prevalence of dementia globally

Light and flow regimes regulate the metabolism of rivers

Mean annual temperature and mean annual precipitation drive much of the variation in productivity across Earth's terrestrial ecosystems but do not explain variation in gross primary productivity (GPP) or ecosystem respiration (ER) in flowing waters. We document substantial variation in the magnitude and seasonality of GPP and ER across 222 US rivers. In contrast to their terrestrial counterparts, most river ecosystems respire far more carbon than they fix and have less pronounced and consistent seasonality in their metabolic rates. We find that variation in annual solar energy inputs and stability of flows are the primary drivers of GPP and ER across rivers. A classification schema based on these drivers advances river science and informs management.We thank Ted Stets, Jordan Read, Tom Battin, Sophia Bonjour, Marina Palta, and members of the Duke River Center for their help in developing these ideas. This work was supported by grants from the NSF 1442439 (to E.S.B. and J.W.H.), 1834679 (to R.O.H.), 1442451 (to R.O.H.), 2019528 (to R.O.H. and J.R.B.), 1442140 (to M.C.), 1442451 (to A.M.H.), 1442467 (to E.H.S.), 1442522 (to N.B.G.), 1624807 (to N.B.G.), and US Geological Survey funding for the working group was supported by the John Wesley Power Center for Analysis and Synthesis. Phil Savoy contributed as a postdoc- toral associate at Duke University and as a postdoctoral associate (contractor) at the US Geological Survey

Many Ribosomal Protein Genes Are Cancer Genes in Zebrafish

We have generated several hundred lines of zebrafish (Danio rerio), each heterozygous for a recessive embryonic lethal mutation. Since many tumor suppressor genes are recessive lethals, we screened our colony for lines that display early mortality and/or gross evidence of tumors. We identified 12 lines with elevated cancer incidence. Fish from these lines develop malignant peripheral nerve sheath tumors, and in some cases also other tumor types, with moderate to very high frequencies. Surprisingly, 11 of the 12 lines were each heterozygous for a mutation in a different ribosomal protein (RP) gene, while one line was heterozygous for a mutation in a zebrafish paralog of the human and mouse tumor suppressor gene, neurofibromatosis type 2. Our findings suggest that many RP genes may act as haploinsufficient tumor suppressors in fish. Many RP genes might also be cancer genes in humans, where their role in tumorigenesis could easily have escaped detection up to now

Comparative Oncogenomic Analysis of Copy Number Alterations in Human and Zebrafish Tumors Enables Cancer Driver Discovery

The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs) are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs). Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. We established a list of orthologous genes between human and zebrafish, which includes approximately two-thirds of human protein-coding genes. For the subset of these genes found in human MPNST CNAs, only one quarter of their orthologues were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.Kathy and Curt Marble Cancer Research FundArthur C. MerrillNational Institutes of Health (U.S.) (Grant CA106416)National Institutes of Health (U.S.) (Grant ROI RR020833)National Institutes of Health (U.S.) (Grant 1F32GM095213-01

Provider perceptions of a humanizing intervention for healthcare workers - a survey study of PPE Portraits

INTRODUCTION: Reports from patients and healthcare workers dealing with COVID-19 underscore experiences of isolation and fear. Some of this experience results from the distancing effect of masks, gloves, and gowns known as Personal Protective Equipment (PPE). One approach to bridging the divide created by PPE is the use of PPE Portraits, postcard-sized pictures affixed to PPE. OBJECTIVE: Our confidential, email-based survey aimed to quantify provider attitudes towards PPE Portraits. METHODS: PPE Portraits were piloted at an academic, safety-net health system experiencing a COVID-19 patient surge in April-May 2020, necessitating use of full PPE for COVID-positive patients and surgical masks in all hospital settings. Our survey assessed staff exposure to PPE Portraits, attitudes towards PPE Portraits, and potential program expansion. For staff wearing PPE Portraits, we also assessed perceptions of interactions with other staff and patients/families and impact on personal wellbeing. The University of Massachusetts Medical School\u27s IRB designated this a quality improvement project (#H00020279). RESULTS: Over half of survey respondents (n=111/173, 64%) reported exposure to PPE Portraits. Attitudes towards PPE Portraits were positive overall, with agreement that PPE Portraits were a good idea (89%), improved provider mood (79%), enhanced perception of team connection (72%) and more positive among those who reported exposure. Open-ended responses (n=41) reinforced positive survey data, and also raised concerns about infection control (n=6), cost/logistics (n=5), and provider vulnerability (n=3). CONCLUSIONS: Providers report that PPE Portraits may represent a positive, patient-centered idea that helps reassure patients, is well-received by interdisciplinary staff, and may enhance patient and team interactions. Potential adaptations to address concerns include photo pins, and donor/ patient and family experience department support for costs. KEY MESSAGE: This article describes a cross-sectional study that investigated provider perceptions on the use of PPE Portraits, an intervention that addresses the barrier to patient-provider connection presented by the use of PPE. The results suggest that implementation of the PPE Portrait Project is feasible, acceptable, and effective