Energy-Efficiency Programs: A Supplemental Guide for Small Manufacturing Businesses.

This research was focused on small manufacturing businesses and energy-efficiency programs on the federal, state, and local levels. Small manufacturing businesses have many types of energy-efficiency programs available to them from several different sources. Sources of information for these programs provide technical explanations that are difficult to understand. In addition, different qualifications are required for participation in different programs. The intention of this research was to form a manual for small manufacturing businesses that are energy-intensive. The purpose of the manual is to make the information about energy-efficiency programs more accessible and comprehendible for owners and managers of small manufacturing businesses

PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy

PPM1D encodes a phosphatase that is recurrently activated across cancer, most notably in therapy-related myeloid neoplasms. However, the function of PPM1D in hematopoiesis and its contribution to tumor cell growth remain incompletely understood. Using conditional mouse models, we uncover a central role for Ppm1d in hematopoiesis and validate its potential as a therapeutic target. We find that Ppm1d regulates the competitive fitness and self-renewal of hematopoietic stem cells (HSCs) with and without exogenous genotoxic stresses. We also show that while Ppm1d activation confers cellular resistance to cytotoxic therapy, it does so to a lesser degree than p53 loss, informing the clonal competition phenotypes often observed in human studies. Notably, loss of Ppm1d sensitizes leukemias to cytotoxic therapies in vitro and in vivo, even in the absence of a Ppm1d mutation. Vulnerability to PPM1D inhibition is observed across many cancer types and dependent on p53 activity. Importantly, organism-wide loss of Ppm1d in adult mice is well tolerated, supporting the tolerability of pharmacologically targeting PPM1D. Our data link PPM1D gain-of-function mutations to the clonal expansion of HSCs, inform human genetic observations, and support the therapeutic targeting of PPM1D in cancer

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Listening in on difficult conversations: an observational, multi-center investigation of real-time conversations in medical oncology

BACKGROUND: The quality of communication in medical care has been shown to influence health outcomes. Cancer patients, a highly diverse population, communicate with their clinical care team in diverse ways over the course of their care trajectory. Whether that communication happens and how effective it is may relate to a variety of factors including the type of cancer and the patient’s position on the cancer care continuum. Yet, many of the routine needs of cancer patients after initial cancer treatment are often not addressed adequately. Our goal is to identify areas of strength and areas for improvement in cancer communication by investigating real-time cancer consultations in a cross section of patient-clinician interactions at diverse study sites. METHODS/DESIGN: In this paper we describe the rationale and approach for an ongoing observational study involving three institutions that will utilize quantitative and qualitative methods and employ a short-term longitudinal, prospective follow-up component to investigate decision-making, key topics, and clinician-patient-companion communication dynamics in clinical oncology. DISCUSSION: Through a comprehensive, real-time approach, we hope to provide the fundamental groundwork from which to promote improved patient-centered communication in cancer care

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The impact of PICALM genetic variations on reserve capacity of posterior cingulate in AD continuum

Phosphatidylinositolbinding clathrin assembly protein (PICALM) gene is one novel genetic player associated with late-onset Alzheimer’s disease (LOAD), based on recent genome wide association studies (GWAS). However, how it affects AD occurrence is still unknown. Brain reserve hypothesis highlights the tolerant capacities of brain as a passive means to fight against neurodegenerations. Here, we took the baseline volume and/or thickness of LOAD-associated brain regions as proxies of brain reserve capacities and investigated whether PICALM genetic variations can influence the baseline reserve capacities and the longitudinal atrophy rate of these specific regions using data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. In mixed population, we found that brain region significantly affected by PICALM genetic variations was majorly restricted to posterior cingulate. In sub-population analysis, we found that one PICALM variation (C allele of rs642949) was associated with larger baseline thickness of posterior cingulate in health. We found seven variations in health and two variations (rs543293 and rs592297) in individuals with mild cognitive impairment were associated with slower atrophy rate of posterior cingulate. Our study provided preliminary evidences supporting that PICALM variations render protections by facilitating reserve capacities of posterior cingulate in non-demented elderly

A qualitative exploration of experiences accessing community and social services among pregnant low-income people of color during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic has been associated with increased social and economic stressors among pregnant individuals. While community and social services have been available to mitigate stressors in pregnancy (e.g. food insecurity and financial hardship) and reduce the risk of adverse maternal outcomes, it is unclear how the pandemic impacted access to these resources, particularly in communities of color with lower incomes.ObjectiveTo examine the experiences accessing community and social service resources during the COVID-19 pandemic among pregnant people of color with low incomes.DesignParticipants for this COVID-related qualitative study were recruited from two sources-a prospective comparative effectiveness study of two models of enhanced prenatal care and the California Black Infant Health Program between August and November of 2020.MethodsWe conducted 62 interviews with Medicaid-eligible participants in California's Central Valley. During their interviews, study participants were asked to share their pregnancy-related experiences, including how they felt the pandemic had affected those experiences.ResultsWe identified two broad themes: challenges with accessing community and social service resources during the pandemic and opportunities for improving access to these resources. Sub-themes related to challenges experienced included difficulty with remote access, convoluted enrollment processes for community and social services, and problems specific to accessing COVID-19 resources (e.g. testing). Sub-themes related to opportunities to improve access included leveraging instrumental support from perinatal staff and informational (e.g. practical) support from other community programs and pregnant peers. Participant recommendations included leveraging opportunities to improve client experiences through increased transparency and better patient-provider communication.ConclusionThis study highlights some important trends that emerged with the rollout of remote service delivery for social services among a vulnerable population. Many participants were able to leverage support through other programs and perinatal staff. These individuals identified additional opportunities to improve client experiences that can inform the future implementation of support services for pregnant people

“It was just one moment that I felt like I was being judged”: Pregnant and postpartum black Women's experiences of personal and group-based racism during the COVID-19 pandemic

BackgroundRacial inequities in maternal and child health outcomes persist: Black women and birthing people experience higher rates of adverse outcomes than their white counterparts. Similar inequities are seen in coronavirus disease (COVID-19) mortality rates. In response, we sought to explore the intersections of racism and the COVID-19 pandemic impact on the daily lives and perinatal care experiences of Black birthing people.MethodsWe used an intrinsic case study approach grounded in an intersectional lens to collect stories from Black pregnant and postpartum people residing in Fresno County (July-September 2020). All interviews were conducted on Zoom without video and were audio recorded and transcribed. Thematic analysis was used to group codes into larger themes.ResultsOf the 34 participants included in this analysis, 76.5% identified as Black only, and 23.5% identified as multiracial including Black. Their mean age was 27.2 years [SD, 5.8]. Nearly half (47%) reported being married or living with their partner; all were eligible for Medi-Cal insurance. Interview times ranged from 23 to 96 min. Five themes emerged: (1) Tensions about Heightened Exposure of Black Lives Matter Movement during the pandemic; (2) Fear for Black Son's Safety; (3) Lack of Communication from Health Care Professionals; (4) Disrespect from Health Care Professionals; and (5) Misunderstood or Judged by Health Care Professionals. Participants stressed that the Black Lives Matter Movement is necessary and highlighted that society views their Black sons as a threat. They also reported experiencing unfair treatment and harassment while seeking perinatal care.ConclusionsBlack women and birthing people shared that exposure to racism has heightened during the COVID-19 pandemic, increasing their levels of stress and anxiety. Understanding how racism impacts Black birthing people's lives and care experiences is critical to reforming the police force and revising enhanced prenatal care models to better address their needs

Disruption of the MYC Super-Enhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia.

Mutations in Fms-like tyrosine kinase 3 (FLT3) are common drivers in acute myeloid leukemia (AML) yet FLT3 inhibitors only provide modest clinical benefit. Prior work has shown that inhibitors of lysine-specific demethylase 1 (LSD1) enhance kinase inhibitor activity in AML. Here we show that combined LSD1 and FLT3 inhibition induces synergistic cell death in FLT3-mutant AML. Multi-omic profiling revealed that the drug combination disrupts STAT5, LSD1, and GFI1 binding at the MYC blood super-enhancer, suppressing super-enhancer accessibility as well as MYC expression and activity. The drug combination simultaneously results in the accumulation of repressive H3K9me1 methylation, an LSD1 substrate, at MYC target genes. We validated these findings in 72 primary AML samples with the nearly every sample demonstrating synergistic responses to the drug combination. Collectively, these studies reveal how epigenetic therapies augment the activity of kinase inhibitors in FLT3-ITD AML. Implications: This work establishes the synergistic efficacy of combined FLT3 and LSD1 inhibition in FLT3-ITD AML by disrupting STAT5 and GFI1 binding at the MYC blood-specific super-enhancer complex