A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast.

Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mastectomies. From more than 800,000 cells we identified 41 cell subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according to the natural history of the tissue. Age, parity and germline mutations, known to modulate the risk of developing breast cancer, affected the homeostatic cellular state of the breast in different ways. We found that immune cells from BRCA1 or BRCA2 carriers had a distinct gene expression signature indicative of potential immune exhaustion, which was validated by immunohistochemistry. This suggests that immune-escape mechanisms could manifest in non-cancerous tissues very early during tumor initiation. This atlas is a rich resource that can be used to inform novel approaches for early detection and prevention of breast cancer.

Predictors of intent to utilize the emergency department among a free clinic's patients.

OBJECTIVE: Primary care use helps reduce utilization of more expensive modes of care, such as the emergency department (ED). Although most studies have investigated this association among patients with insurance, few have done so for patients without insurance. We used data from a free clinic network to assess the association between free clinic use and intent to use the ED. METHODS: Data were collected from a free clinic network's electronic health records on adult patients from January 2015 to February 2020. Our outcome was whether patients reported themselves as 'very likely' to visit the ED if the free clinics were unavailable. The independent variable was frequency of free clinic use. Using a multivariable logistic regression model, we controlled for other factors, such as patient demographic factors, social determinants of health, health status, and year effect. RESULTS: Our sample included 5008 visits. When controlling for other factors, higher odds of expressing ED interest were observed for patients who are non-Hispanic Black, older, not married, lived with others, had lower education, were homeless, had personal transportation, lived in rural areas, and had a higher comorbidity burden. In sensitivity analyses, higher odds were observed for dental, gastrointestinal, genitourinary, musculoskeletal, or respiratory conditions. CONCLUSIONS: In the free clinic space, several patient demographic, social determinants of health and medical conditions were independently associated with greater odds of reporting intent on visiting the ED. Additional interventions that improve access and use of free clinics (e.g., dental) may keep patients without insurance from the ED.

July effect in clinical outcomes of esophagogastroduodenoscopy performed at teaching hospitals in the United States.

Background: Esophagogastroduodenoscopy (EGD) is a common procedure used for both diagnosis and treatment, but carries risks such as bleeding and perforation. The "July effect"-described as increased complication rates during the transition of new trainees-has been studied in other procedures, but has not been thoroughly evaluated for EGD. Methods: We used the National Inpatient Sample database for 2016 to 2018 to compare outcomes in EGD performed between July to September and April to June. Results: Approximately 0.91 million patients in the study received EGD between July to September (49.35%) and April to June (50.65%), with no significant differences between the two groups in terms of age, gender, race, income, or insurance status. Of the 911,235 patients, 19,280 died during the study period following EGD, 2.14% (July-September) vs 1.95% (April-June), with an adjusted odds ratio of 1.09 (P < 0.01). The adjusted total hospitalization charge was $2052 higher in July-September ($81,597) vs April to June ($79,023) (P < 0.005). The mean length of stay was 6.8 days (July-September) vs 6.6 days (April-June) (P < 0.001). Conclusions: The results of this study are reassuring as the July effect on inpatient outcomes for EGDs was not significantly different according to our study. We recommend seeking prompt treatment and improving new trainee training and interspecialty communication for better patient outcomes.

Incidental Perforation of Aortic Valve Leaflet Found on Presentation of Cardiogenic Shock.

Aortic regurgitation (AR) is grouped into acute or chronic AR. Acute AR, unlike chronic AR, can manifest with significant hemodynamic compromise. Acute AR is typically due to endocarditis or aortic dissection, and less commonly due to blunt trauma or iatrogenic causes. We present a patient with cardiogenic shock due to severe acute AR from anterior leaflet perforation without an identifiable rheumatologic or infectious etiology.

Ice nucleation in a Gram-positive bacterium isolated from precipitation depends on a polyketide synthase and non-ribosomal peptide synthetase.

Earth's radiation budget and frequency and intensity of precipitation are influenced by aerosols with ice nucleation activity (INA), i.e., particles that catalyze the formation of ice. Some bacteria, fungi, and pollen are among the most efficient ice nucleators but the molecular basis of INA is poorly understood in most of them. Lysinibacillus parviboronicapiens (Lp) was previously identified as the first Gram-positive bacterium with INA. INA of Lp is associated with a secreted, nanometer-sized, non-proteinaceous macromolecule or particle. Here a combination of comparative genomics, transcriptomics, and a mutant screen showed that INA in Lp depends on a type I iterative polyketide synthase and a non-ribosomal peptide synthetase (PKS-NRPS). Differential filtration in combination with gradient ultracentrifugation revealed that the product of the PKS-NRPS is associated with secreted particles of a density typical of extracellular vesicles and electron microscopy showed that these particles consist in "pearl chain"-like structures not resembling any other known bacterial structures. These findings expand our knowledge of biological INA, may be a model for INA in other organisms for which the molecular basis of INA is unknown, and present another step towards unraveling the role of microbes in atmospheric processes.

Innovation in resuscitation: A novel clinical decision display system for advanced cardiac life support.

INTRODUCTION: The Advanced Cardiac Life Support (ACLS) Clinical Decision Display System (CDDS) is a novel application designed to optimize team organization and facilitate decision-making during ACLS resuscitations. We hypothesized that resuscitation teams would more consistently adhere to ACLS guideline time intervals in simulated resuscitation scenarios with the CDDS compared to without. METHODS: We conducted a simulation-based, non-blinded, randomized, crossover-design study with resuscitation teams comprised of Emergency Medicine physicians, registered nurses, critical care technicians, and paramedics. Each team performed 4 ACLS scenarios in randomized sequences, half with the CDDS and half without. We analyzed the resuscitations and recorded the times of interventions that have defined intervals by ACLS: rhythm checks, epinephrine administration, and shock delivery. In addition, we surveyed each resuscitation team regarding their experience using the CDDS. RESULTS: On average, teams performed rhythm checks 4.9 s closer to ACLS guidelines with the CDDS (p = 0.0358). Teams were also more consistent; on average, teams reduced the variation of time between consecutive doses of epinephrine by 45% (p = 0.0001) and defibrillation by 47% (p < 0.0001). Ninety-eight percent of participants indicated they would use the CDDS if available in real cardiac arrests. CONCLUSIONS: This study demonstrates that the CDDS improves the accuracy and precision of timed ACLS interventions in a simulated setting. Resuscitation teams were strongly in favor of utilizing the CDDS in clinical practice. Further investigations of the introduction of the platform into real time clinical environments will be needed to assess true efficacy and patient outcomes.

The greater snow goose Anser caerulescens atlanticus: Managing an overabundant population.

Between the early 1900s and the 1990s, the greater snow goose Anser caerulescens atlanticus population grew from 3000 individuals to more than 700 000. Because of concerns about Arctic degradation of natural habitats through overgrazing, a working group recommended the stabilization of the population. Declared overabundant in 1998, special management actions were then implemented in Canada and the United States. Meanwhile, a cost-benefit socioeconomic analysis was performed to set a target population size. Discussions aiming towards attaining a common vision were undertaken with stakeholders at multiple levels. The implemented measures have had varying success; but population size has been generally stable since 1999. To be effective and meet social acceptance, management actions must have a scientific basis, result from a consensus among stakeholders, and include an efficient monitoring programme. In this paper, historical changes in population size and management decisions along with past and current challenges encountered are discussed.

Effect of investigator observation on gait parameters in individuals with and without chronic low back pain.

Despite the ubiquity of gait assessment in clinic and research, it is unclear how observation impacts gait, particularly in persons with chronic pain and psychological stress. We compared temporal spatial gait patterns in people with and without chronic low back pain (CLBP) when they were aware and unaware of being observed. This was a repeated-measures, deception study in 55 healthy persons (32.0±12.4 yr, 24.2±2.7kg/m2) and persons with CLBP (51.9±17.9 yr, 27.8±4.4kg/m2). Participants performed one condition in which they were unaware of observation (UNW), and three conditions under investigator observation: (1) aware of observation (AWA), (2) investigators watching cadence, (3) investigators watching step length. Participants walked across an 8.4m gait mat, while temporal spatial parameters of gait were collected. The Medical Outcomes Short Form (SF-12), Beck Depression Inventory (BDI), State Trait Anxiety Inventory (STAI), and Oswestry Disability Index (ODI) were completed. Significant condition by group interactions were found for velocity and step length (p<0.05). Main effects of study condition existed for all gait variables except for step width. Main effects of group (healthy, LBP) were significant for all variables except for step width (p<0.05). Regression analyses revealed that after accounting for age, sex, and SF-12 mental component score, BDI scores predict velocity changes during walking from the UNW to AWA conditions. These findings show that people change their gait patterns when being observed. Gait analyses may require additional trials before data can reliably be interpreted and used for clinical decision-making.

Mid-term shoulder functional and quality of life outcomes after shoulder replacement in obese patients.

BACKGROUND: Shoulder pain and loss of function are directly associated with obesity. QUESTIONS/PURPOSES: We hypothesized that significant interactions would exist between total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RSA) and obesity status on functional and quality of life (QOL) outcomes over the long term. Clinical and QOL outcomes (American Shoulder and Elbow Surgeons Evaluation form, Shoulder Pain and Disability Index, University of California at Los Angeles Shoulder Rating scale, Medical Outcomes Short Form 12 (SF-12), range of motion (ROM), and strength) were longitudinally compared in patients with low and high body mass index (BMI) after a TSA or a RSA. Prospectively collected data of patients with a TSA or RSA were reviewed (N = 310). Preoperative, 2-year, and final follow-up visits were included (range 3-17 years; mean 5.0 ± 2.5 years). Patient data were stratified for analysis using BMI. RESULTS: Morbidly obese patients had worse preoperative functional scores and QOL compared to the other groups. There were no significant interactions of BMI group by surgery type for any of the outcome variables except for active external rotation ROM. Morbidly obese patients attained lower SF-12 scores compared to the remaining groups at each time point. CONCLUSIONS: Both TSA and RSA can be expected to impart positive functional outcomes in patients irrespective of BMI. Morbidly obese patients do not attain the same gains in Medical Outcomes SF-12 scores as the non-morbidly obese patients. The lower improvements in active external ROM may be due to morphological limitations of excessive adiposity. LEVEL OF EVIDENCE: This is a level II study.

Anthropocene streams and base-level controls from historic dams in the unglaciated mid-Atlantic region, USA.

Recently, widespread valley-bottom damming for water power was identified as a primary control on valley sedimentation in the mid-Atlantic US during the late seventeenth to early twentieth century. The timing of damming coincided with that of accelerated upland erosion during post-European settlement land-use change. In this paper, we examine the impact of local drops in base level on incision into historic reservoir sediment as thousands of ageing dams breach. Analysis of lidar and field data indicates that historic milldam building led to local base-level rises of 2-5 m (typical milldam height) and reduced valley slopes by half. Subsequent base-level fall with dam breaching led to an approximate doubling in slope, a significant base-level forcing. Case studies in forested, rural as well as agricultural and urban areas demonstrate that a breached dam can lead to stream incision, bank erosion and increased loads of suspended sediment, even with no change in land use. After dam breaching, key predictors of stream bank erosion include number of years since dam breach, proximity to a dam and dam height. One implication of this work is that conceptual models linking channel condition and sediment yield exclusively with modern upland land use are incomplete for valleys impacted by milldams. With no equivalent in the Holocene or late Pleistocene sedimentary record, modern incised stream-channel forms in the mid-Atlantic region represent a transient response to both base-level forcing and major changes in land use beginning centuries ago. Similar channel forms might also exist in other locales where historic milling was prevalent.

Seasonal variation in growth of greater snow goose goslings: the role of food supply.

Even though growth rate is an important fitness component, it is still controversial to what extent parent birds adjust the timing of offspring hatch to natural variations in food supply to maximize offspring growth. We studied the role of food availability in explaining inter- and intra-seasonal variation of growth rate in goslings of greater snow geese over 5 years. The peak of hatching generally coincided with the peak of food availability. However, early-hatched goslings usually grew faster than birds hatched at the peak, which in␣turn grew faster than late-hatched goslings, although this phenomenon was not observed in all years. There was considerable variation in growth rate among the five years, the smallest goslings produced in the best year (1991) being larger than the largest goslings of the poorest year (1994). We developed three indices of food availability, based on the cumulative availability of plant biomass and nitrogen content during the growth period, and showed that the cumulative exposure to nitrogen biomass explained up to 43% of variation (intra- and inter-annual) in body size just before fledging. In years with good feeding conditions, early-hatched goslings had access to more nitrogen during their growing period than those hatching on or after the peak and they grew faster. In years of lower food availability, early-hatched goslings had no detectable advantage over peak- or late-hatched birds for access to protein-rich food and no seasonal decline in growth rate was observed. These results confirm the critical role of food supply in the seasonal variation of growth rate in Arctic-nesting geese.