Aerosol and cloud microphysics covariability in the northeast Pacific boundary layer estimated with ship-based and satellite remote sensing observations

Ship measurements collected over the northeast Pacific along transects between the port of Los Angeles (33.7°N, 118.2°W) and Honolulu (21.3°N, 157.8°W) during May to August 2013 were utilized to investigate the covariability between marine low cloud microphysical and aerosol properties. Ship-based retrievals of cloud optical depth (τ) from a Sun photometer and liquid water path (LWP) from a microwave radiometer were combined to derive cloud droplet number concentration Nd and compute a cloud-aerosol interaction (ACI) metric defined as ACICCN = ∂ ln(Nd)/∂ ln(CCN), with CCN denoting the cloud condensation nuclei concentration measured at 0.4% (CCN0.4) and 0.3% (CCN0.3) supersaturation. Analysis of CCN0.4, accumulation mode aerosol concentration (Na), and extinction coefficient (σext) indicates that Na and σext can be used as CCN0.4 proxies for estimating ACI. ACICCN derived from 10 min averaged Nd and CCN0.4 and CCN0.3, and CCN0.4 regressions using Na and σext, produce high ACICCN: near 1.0, that is, a fractional change in aerosols is associated with an equivalent fractional change in Nd. ACICCN computed in deep boundary layers was small (ACICCN = 0.60), indicating that surface aerosol measurements inadequately represent the aerosol variability below clouds. Satellite cloud retrievals from MODerate-resolution Imaging Spectroradiometer and GOES-15 data were compared against ship-based retrievals and further analyzed to compute a satellite-based ACICCN. Satellite data correlated well with their ship-based counterparts with linear correlation coefficients equal to or greater than 0.78. Combined satellite Nd and ship-based CCN0.4 and Na yielded a maximum ACICCN = 0.88–0.92, a value slightly less than the ship-based ACICCN, but still consistent with aircraft-based studies in the eastern Pacific

Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects.

Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development

A thematic analysis of shared experiences of essential health and support personnel in the COVID-19 pandemic.

AIMS AND OBJECTIVES: Studies have shown that the COVID-19 pandemic has taken a toll on individuals who interact with patients with SARS-CoV-2 but focused largely on clinicians in acute care settings. This qualitative descriptive study aimed to understand the experiences and well-being of essential workers across settings during the pandemic. BACKGROUND: Multiple studies of the well-being of individuals who have cared for patients during the pandemic have included interviews of clinicians from acute care settings and revealed high levels of stress. However, other essential workers have not been included in most of those studies, yet they may also experience stress. METHODS: Individuals who participated in an online study of anxiety, depression, traumatic distress, and insomnia, were invited to provide a free-text comment if they had anything to add. A total of 2,762 essential workers (e.g., nurses, physicians, chaplains, respiratory therapists, emergency medical technicians, housekeeping, and food service staff, etc.) participated in the study with 1,079 (39%) providing text responses. Thematic analysis was used to analyze those responses. RESULTS: Four themes with eight sub-themes were: Facing hopelessness, yet looking for hope; Witnessing frequent death; Experiencing disillusionment and disruption within the healthcare system, and Escalating emotional and physical health problems. CONCLUSIONS: The study revealed major psychological and physical stress among essential workers. Understanding highly stressful experiences during the pandemic is essential to identify strategies that ameliorate stress and prevent its negative consequences. This study adds to the research on the psychological and physical impact of the pandemic on workers, including non-clinical support personnel often overlooked as experiencing major negative effects. RELEVANCE TO CLINICAL PRACTICE: The magnitude of stress among all levels of essential workers suggests the need to develop strategies to prevent or alleviate stress across disciplines and all categories of workers

Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections

Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas Aeruginosa

Background: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). Methods: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). Results: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941). Conclusions: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs

Mechanisms of congenital heart disease caused by NAA15 haploinsufficiency

Rationale: NAA15 is a component of the N-terminal (Nt) acetyltransferase complex, NatA. The mechanism by which NAA15 haploinsufficiency causes congenital heart disease (CHD) remains unknown. To better understand molecular processes by which NAA15 haploinsufficiency perturbs cardiac development, we introduced NAA15 variants into human induced pluripotent stem cells (iPSCs) and assessed the consequences of these mutations on RNA and protein expression. Objective: We aim to understand the role of NAA15 haploinsufficiency in cardiac development by investigating proteomic effects on NatA complex activity, and identifying proteins dependent upon a full amount of NAA15. Methods and Results: We introduced heterozygous LoF, compound heterozygous and missense residues (R276W) in iPS cells using CRISPR/Cas9. Haploinsufficient NAA15 iPS cells differentiate into cardiomyocytes, unlike NAA15-null iPS cells, presumably due to altered composition of NatA. Mass spectrometry (MS) analyses reveal ~80% of identified iPS cell NatA targeted proteins displayed partial or complete Nt-acetylation. Between null and haploinsufficient NAA15 cells Nt-acetylation levels of 32 and 9 NatA-specific targeted proteins were reduced, respectively. Similar acetylation loss in few proteins occurred in NAA15 R276W iPSCs. In addition, steady-state protein levels of 562 proteins were altered in both null and haploinsufficient NAA15 cells; eighteen were ribosomal-associated proteins. At least four proteins were encoded by genes known to cause autosomal dominant CHD. Conclusions: These studies define a set of human proteins that requires a full NAA15 complement for normal synthesis and development. A 50% reduction in the amount of NAA15 alters levels of at least 562 proteins and Nt-acetylation of only 9 proteins. One or more modulated proteins are likely responsible for NAA15-haploinsufficiency mediated CHD. Additionally, genetically engineered iPS cells provide a platform for evaluating the consequences of amino acid sequence variants of unknown significance on NAA15 function

ICDP workshop on the Lake Tanganyika Scientific Drilling Project: a late Miocene–present record of climate, rifting, and ecosystem evolution from the world's oldest tropical lake

The Neogene and Quaternary are characterized by enormous changes in global climate and environments, including global cooling and the establishment of northern high-latitude glaciers. These changes reshaped global ecosystems, including the emergence of tropical dry forests and savannahs that are found in Africa today, which in turn may have influenced the evolution of humans and their ancestors. However, despite decades of research we lack long, continuous, well-resolved records of tropical climate, ecosystem changes, and surface processes necessary to understand their interactions and influences on evolutionary processes. Lake Tanganyika, Africa, contains the most continuous, long continental climate record from the mid-Miocene (∼10 Ma) to the present anywhere in the tropics and has long been recognized as a top-priority site for scientific drilling. The lake is surrounded by the Miombo woodlands, part of the largest dry tropical biome on Earth. Lake Tanganyika also harbors incredibly diverse endemic biota and an entirely unexplored deep microbial biosphere, and it provides textbook examples of rift segmentation, fault behavior, and associated surface processes. To evaluate the interdisciplinary scientific opportunities that an ICDP drilling program at Lake Tanganyika could offer, more than 70 scientists representing 12 countries and a variety of scientific disciplines met in Dar es Salaam, Tanzania, in June 2019. The team developed key research objectives in basin evolution, source-to-sink sedimentology, organismal evolution, geomicrobiology, paleoclimatology, paleolimnology, terrestrial paleoecology, paleoanthropology, and geochronology to be addressed through scientific drilling on Lake Tanganyika. They also identified drilling targets and strategies, logistical challenges, and education and capacity building programs to be carried out through the project. Participants concluded that a drilling program at Lake Tanganyika would produce the first continuous Miocene–present record from the tropics, transforming our understanding of global environmental change, the environmental context of human origins in Africa, and providing a detailed window into the dynamics, tempo and mode of biological diversification and adaptive radiations.© Author(s) 2020. This open access article is distributed under the Creative Commons Attribution 4.0 License

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Liability Under CERCLA § 9601 (35)(C ) for Intermediate Landowners Who Discover Contamination, Do Not Disclose, and Sell to Innocent Buyers

Section 9601(35)(C) of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) may amend the traditional classes of liable parties, holding responsible intermediate land-owners who convey properties without disclosing their knowledge of contamination. To date, however, courts have failed to settle on whether § 9601(35)(C) constitutes a new and independent basis for liability. This Note provides a discussion of the current status of the law on intermediate landowner liability, presents four scenarios in which the lack of consistency in judicial interpretation of § 9601(35)(C) results in mischievous land transfers, and finally, suggests that courts should use the section as an independent basis for intermediate owner liability to achieve the policy goals of CERCLA