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There has been an increasing demand for healthcare analytics skills and competence by healthcare organizations. Although many universities have established programs and courses on healthcare analytics, most of these curricula have been designed for information systems (IS), information technology (IT), or analytics students. It is unclear how these curricula would fit the needs of healthcare professionals who have little IT knowledge and background yet also need analytics for their clinical or administrative job roles. This research reports on the design of an executive MBA course intended for an audience of healthcare professionals. The learning objectives, topic coverage, software tools, and assessment methods are presented along with students' perceptions of these aspects of the course. Several important lessons learned are shared and future directions are proposed, which can help other educators design similar healthcare analytics courses for professional audiences.

Ihuoma Eneli,1,2 Jinyu Xu,1 Matthew Webster,3 Amy McCagg,3 Lex Van Der Ploeg,3 Alastair S Garfield,3 Elizabeth Estrada41Center for Healthy Weight and Nutrition, Nationwide Children’s Hospital, Columbus, OH, USA; 2Department of Pediatrics, The Ohio State University, Columbus, OH, USA; 3Department of Medical Communications, Rhythm Pharmaceuticals, Inc, Boston, MA, USA; 4Department of Pediatric Endocrinology, University of North Carolina, Chapel Hill, NC, USAPurpose: The hypothalamic melanocortin-4 receptor (MC4R) pathway, a component of the central melanocortin pathway, regulates energy balance and satiety. Rare genetic disorders of obesity may be characterized by impaired MC4R pathway signaling, which results in early-onset severe obesity and insatiable hunger (hyperphagia). The TEMPO registry (NCT03479437) is a voluntary, prospective, open-ended registry of individuals with rare genetic disorders of obesity due to mutations in genes within the MC4R pathway who have early-onset severe obesity. The objective of the TEMPO registry is to evaluate the burden of rare genetic disorders of obesity on individuals, their parents/caregivers, health care providers, and the health care system.Patients and methods: Individuals with rare genetic disorders of obesity (adults aged ≥18 years and children and adolescents aged from 2 to 17 years) will be referred by their health care providers or by a genetic screening study. Individuals must meet age- and sex-specific body mass index values that define the clinical criteria for severe obesity and carry selected variants in MC4R or in one of several genes upstream or downstream of the MC4R. Online surveys will be completed by the individual, parent/caregiver, and health care provider at baseline and annually thereafter and will collect data on demographics, results of genetic testing, medical/family history, disease characteristics, resource utilization, eating habits/hunger episodes, social and emotional impacts, and interest in future clinical trial participation.Conclusions: The TEMPO registry will provide insights into the overall course and disease burden for individuals with rare genetic disorders of obesity. Health care providers may use this resource to improve the identification, diagnosis, and treatment of individuals with rare forms of genetic obesity.Keywords: Alström syndrome, Bardet-Biedl syndrome, LEPR, PCSK1, POMC, severe obesity

In April and May of 2020, a large phytoplankton bloom composed primarily of the dinoflagellate Lingulodinium polyedra reached historic levels in geographic expanse, duration, and density along the coast of southern California, United States, and Baja California Norte, Mexico. Here, we report the water quality parameters of dissolved oxygen and pH over the course of the red tide, as measured by multiple sensors deployed in various locations along San Diego County, and document the extent of mass organism mortality using field surveys and community science observations. We found that dissolved oxygen and pH corresponded with bloom dynamics, with extreme hypoxic and hyperoxic conditions occurring at multiple locations along the coast, most notably within select estuaries where dissolved oxygen reached 0 mg L−1 and hypoxia occurred for up to 254 consecutive hours, as well as along the inner shelf of the open coast where dissolved oxygen dropped as low as 0.05 mg L−1. Similarly, pH ranged widely (6.90–8.79) across the bloom over both space and time, largely corresponding with dissolved oxygen level. Extreme changes in dissolved oxygen and pH, in addition to changes to other water parameters that affect organismal health, ultimately led to documented mortalities of thousands of demersal and benthic fishes and invertebrates (primarily within estuarine and inner-shelf environments), and long-term surveys within one lagoon showed protracted changes to benthic infaunal density and species composition. In addition to field observations, we also quantified water quality parameters and organism mortalities from four local aquarium facilities, with varying levels of filtration and artificial oxygenation, and documented the morphological changes in the gills of captive-held Pacific sardine in response to the red tide. We show that multiple factors contributed to organismal stress, with hypoxia likely being the most widespread, but not the only, cause of mortality.

2022 marked the third consecutive La Niña and extended the longest consecutive stretch of negative Oceanic Niño Index since 1998-2001. While physical and biological conditions in winter and spring largely adhered to prior La Niña conditions, summer and fall were very different. Similar to past La Niña events, in winter and spring coastal upwelling was either average or above average, temperature average or below average, salinity generally above average. In summer and fall, however, upwelling and temperature were generally average or slightly below average, salinity was close to average and chlorophyll a was close to average. Again, as during prior La Niña events, biomass of northern/southern copepods was above/below average off Oregon in winter, and body size of North Pacific krill in northern California was above average in winter. By contrast, later in the year the abundance of northern krill dropped off Oregon while southern copepods increased and body sizes of North Pacific krill fell in northern California. Off Oregon and Washington abundances of market squid and Pacific pompano (indicators of warm, non-typical La Niña conditions) were high. In the 20th century, Northern anchovy recruitment tended to be high during cold conditions, but despite mostly warm conditions from 2015-2021 anchovy populations boomed and remained high in 2022. Resident seabird reproductive success, which tended in the past to increase during productive La Niña conditions was highly variable throughout the system as common murre and pelagic cormorant, experienced complete reproductive failure at Yaquina Head, Oregon while Brandt’s cormorant reproduction was average. At three sampling locations off central California, however, common murre reproduction was close to or above average while both pelagic and Brandt’s cormorant were above average. California sealion reproduction has been above average each year since 2016, and pup weight was also above average in 2022, likely in response not to La Niña or El Niño but continuous high abundance of anchovy. The highly variable and often unpredictable physical and biological conditions in 2022 highlight a growing recognition of disconnects between basin-scale indices and local conditions in the CCE. “July-December 2022 is the biggest outlier from individual “strong” La Niña (events) ever going back to the 50s.” – Nate Mantua

Detect-and-avoid (DAA) systems for remotely piloted aircraft systems (RPAS) can provide remain well clear (RWC) guidance as well as shorter term resolution advisories (RAs) for collision avoidance, which are both provided in the vertical and horizontal planes. Simulation-based studies for large sets of encounter scenarios are used in the development and evaluation of DAA systems, which encompass safety and operational acceptability of the DAA supported operations. Given the key role of the remote pilot (RP) in responding to RWC guidance and RAs, a RP model is an essential element in such simulations. This paper describes the development of a RP model for evaluation of encounter scenarios involving the ACAS Xu DAA system. The model describes RP situation awareness (perception, comprehension, projection) as basis for decision-making, modes for responding to RAs and/or RWC guidance, response delays, response strengths, and the flight control actions. The RP model includes deterministic and stochastic settings. It is integrated in a simulation environment for encounters of manned and/or unmanned aircraft, the involved DAA and airborne collision avoidance systems, the surveillance and communication systems, and the human operators. Simulation results are provided for a set of encounters between pairs of RPAS both having ACAS Xu for various configurations of the RP model, and for cases with and without sensor errors. The results show that there can be large differences between the results of deterministic and Monte Carlo simulations, indicating that limited sensor errors can have a large impact on the nonlinear system dynamics. Furthermore it is shown that deadlock conditions can exist where the RPAS show oscillatory behaviour and do not manage to effectively pass each other, dependent on the encounter geometry and RP model settings. It is advised to perform a broad sensitively study for RP performance and to study extending the scope of DAA systems to include guidance for efficiently returning to mission without triggering new conflicts.

Abstract Background Chronic kidney disease (CKD) prevalence is steadily increasing, in part due to increased multimorbidity in our aging global population. When progression to kidney failure cannot be avoided, people need unbiased information to inform decisions about whether to start dialysis, if or when indicated, or continue with holistic person-centred care without dialysis (conservative kidney management). Comparisons suggest that while there may be some survival benefit from dialysis over conservative kidney management, in people aged 80 years and over, or with multiple health problems or frailty, this may be at the expense of quality of life, hospitalisations, symptom burden and preferred place of death. Prepare for Kidney Care aims to compare preparation for a renal dialysis pathway with preparation for a conservative kidney management pathway, in relation to quantity and quality of life in multimorbid, frail, older people with advanced CKD. Methods This is a two-arm, superiority, parallel group, non-blinded, individual-level, multi-centre, pragmatic trial, set in United Kingdom National Health Service (NHS) kidney units. Patients with advanced CKD (estimated glomerular filtration rate

Abstract Background The growth factor receptor bound protein 7 (Grb7) family of signalling adaptor proteins comprises Grb7, Grb10 and Grb14. Each can interact with the insulin receptor and other receptor tyrosine kinases, where Grb10 and Grb14 inhibit insulin receptor activity. In cell culture studies they mediate functions including cell survival, proliferation, and migration. Mouse knockout (KO) studies have revealed physiological roles for Grb10 and Grb14 in glucose-regulated energy homeostasis. Both Grb10 KO and Grb14 KO mice exhibit increased insulin signalling in peripheral tissues, with increased glucose and insulin sensitivity and a modestly increased ability to clear a glucose load. In addition, Grb10 strongly inhibits fetal growth such that at birth Grb10 KO mice are 30% larger by weight than wild type littermates. Results Here, we generate a Grb7 KO mouse model. We show that during fetal development the expression patterns of Grb7 and Grb14 each overlap with that of Grb10. Despite this, Grb7 and Grb14 did not have a major role in influencing fetal growth, either alone or in combination with Grb10. At birth, in most respects both Grb7 KO and Grb14 KO single mutants were indistinguishable from wild type, while Grb7:Grb10 double knockout (DKO) were near identical to Grb10 KO single mutants and Grb10:Grb14 DKO mutants were slightly smaller than Grb10 KO single mutants. In the developing kidney Grb7 had a subtle positive influence on growth. An initial characterisation of Grb7 KO adult mice revealed sexually dimorphic effects on energy homeostasis, with females having a significantly smaller renal white adipose tissue depot and an enhanced ability to clear glucose from the circulation, compared to wild type littermates. Males had elevated fasted glucose levels with a trend towards smaller white adipose depots, without improved glucose clearance. Conclusions Grb7 and Grb14 do not have significant roles as inhibitors of fetal growth, unlike Grb10, and instead Grb7 may promote growth of the developing kidney. In adulthood, Grb7 contributes subtly to glucose mediated energy homeostasis, raising the possibility of redundancy between all three adaptors in physiological regulation of insulin signalling and glucose handling.

We investigated whether CO2-induced ocean acidification (OA) affects dopamine receptor-dependent behavior in bicolor damselfish (Stegastes partitus). Damselfish were kept in aquaria receiving flow through control (pH ~ 8.03; pCO2 ~ 384 μatm) or OA (pH ~ 7.64; CO2 ~ 1100 μatm) seawater at a rate of 1 L min-1. Despite this relatively fast flow rate, fish respiration further acidified the seawater in both control (pH ~7.88; pCO2 ~ 595 μatm) and OA (pH ~7.55; pCO2 ~ 1450 μatm) fish-holding aquaria. After five days of exposure, damselfish locomotion, boldness, anxiety, and aggression were assessed using a battery of behavioral tests using automated video analysis. Two days later, these tests were repeated following application of the dopamine D1 receptor agonist SKF 38393. OA-exposure induced ceiling anxiety levels that were significantly higher than in control damselfish, and SKF 38393 increased anxiety in control damselfish to a level not significantly different than that of OA-exposed damselfish. Additionally, SKF 38393 decreased locomotion and increased boldness in control damselfish but had no effect in OA-exposed damselfish, suggesting an alteration in activity of dopaminergic pathways that regulate behavior under OA conditions. These results indicate that changes in dopamine D1 receptor function affects fish behavior during exposure to OA. However, subsequent measurements of seawater sampled using syringes during the daytime (~3-4 pm local time) from crevasses in coral reef colonies, which are used as shelter by damselfish, revealed an average pH of 7.73 ± 0.03 and pCO2 of 925.8 ± 62.2 μatm; levels which are comparable to Representative Concentration Pathway (RCP) 8.5 predicted end-of-century mean OA levels in the open ocean. Further studies considering the immediate environmental conditions experienced by fish as well as individual variability and effect size are required to understand potential implications of the observed OA-induced behavioral effects on damselfish fitness in the wild.

Introduction In busy clinical settings, there is limited time to teach physical examination (PE) and procedural skills, particularly when the traditional head-to-toe PE approach is time-consuming. Near-peer teaching of a more efficient approach, the hypothesis-driven PE (HDPE), increases students’ learning opportunities. We developed a near-peer HDPE module to improve medical student confidence, knowledge, and skills for diagnosing and managing streptococcal pharyngitis. Methods During this 1-hour module, residents taught the diagnostic approach for a patient with sore throat and facilitated small groups for practicing PE and throat swab skills. We assessed students using pre- and postmodule surveys including Likert-scale confidence scores (1 = not at all confident, 5= extremely confident), multiple-choice knowledge questions, and a skills rubric. A control group was surveyed at clerkship conclusion. Results Of the 71 pediatric clerkship students who participated, 69 (97%) completed premodule surveys and 65 (91%) completed skills assessments. Twenty-eight (39%) completed postmodule surveys and skill assessments. After participation, students’ survey responses and rubrics indicated significant increase in confidence (Mdnpre = 2 [IQR = 1,2], Mdnpost = 4 [IQR = 4,5]; p < .001), knowledge (Mpre = 40%, Mpost = 77%; p < .001), and skills (Mpre = 5.3, Mpost = 7.5; p < .01). Participating students also had significantly higher confidence (p < .005) and knowledge (p < 0.01) compared to the control group. Discussion This near-peer HDPE module improved students’ knowledge, confidence, and skills related to streptococcal pharyngitis diagnosis and management and achieved compliance for a required clerkship skill.

Abstract Background Optimal size at birth dictates perinatal survival and long-term risk of developing common disorders such as obesity, type 2 diabetes and cardiovascular disease. The imprinted Grb10 gene encodes a signalling adaptor protein capable of inhibiting receptor tyrosine kinases, including the insulin receptor (Insr) and insulin-like growth factor type 1 receptor (Igf1r). Grb10 restricts fetal growth such that Grb10 knockout (KO) mice are at birth some 25-35% larger than wild type. Using a mouse genetic approach, we test the widely held assumption that Grb10 influences growth through interaction with Igf1r, which has a highly conserved growth promoting role. Results Should Grb10 interact with Igf1r to regulate growth Grb10:Igf1r double mutant mice should be indistinguishable from Igf1r KO single mutants, which are around half normal size at birth. Instead, Grb10:Igf1r double mutants were intermediate in size between Grb10 KO and Igf1r KO single mutants, indicating additive effects of the two signalling proteins having opposite actions in separate pathways. Some organs examined followed a similar pattern, though Grb10 KO neonates exhibited sparing of the brain and kidneys, whereas the influence of Igf1r extended to all organs. An interaction between Grb10 and Insr was similarly investigated. While there was no general evidence for a major interaction for fetal growth regulation, the liver was an exception. The liver in Grb10 KO mutants was disproportionately overgrown with evidence of excess lipid storage in hepatocytes, whereas Grb10:Insr double mutants were indistinguishable from Insr single mutants or wild types. Conclusions Grb10 acts largely independently of Igf1r or Insr to control fetal growth and has a more variable influence on individual organs. Only the disproportionate overgrowth and excess lipid storage seen in the Grb10 KO neonatal liver can be explained through an interaction between Grb10 and the Insr. Our findings are important for understanding how positive and negative influences on fetal growth dictate size and tissue proportions at birth.

Introduction: Emerging literature links fatherhood to men's health but lacks comprehensive assessment of health outcomes, especially among multiethnic populations. This study's objective was to evaluate the associations of fatherhood (age at onset and status) with cardiovascular health scores, incident cardiovascular disease, cardiovascular disease death, and all-cause mortality, examining differences by race/ethnicity. Methods: The study sample included men from Multi-Ethnic Study of Atherosclerosis, prospective cohort study that enrolled adults aged 45–84 years without known cardiovascular disease at baseline. Cardiovascular health was defined using the American Heart Association's Life's Essential 8 scores (0–100), excluding sleep (cardiovascular health score). Results: In this sample of 2,814 men, mean age at cardiovascular health assessment was 62.2 years, 82% were fathers, 24% self-identified as Black, 13% self-identified Chinese, 22% self-identified Hispanic, and 41% self-identified White. Fathers who were aged 35 years (adjusted mean score of 61.1 vs 64.7 [p=0.01] and 61.0 vs 64.7 [p

Background: Cervical ripening is crucial for induction. However, its influencing factors, mechanistic understanding, and effective risk stratification are still challenging. Recent research suggested that microorganisms and their metabolites in vaginal spaces correlate to preterm birth. However, it remains unclear whether the cervicovaginal metabolome is related to the natural physiological process of cervical maturation. Objective: We aimed to analyze the cervicovaginal metabolome in women with favorable induction cervix and those unfavorable for induction when delivering at term. Study design: Cervicovaginal swabs were collected between 40 and 41 weeks gestation from the following 2 different groups of patients: Ripe group (n = 25) which was favorable for the induction cervix and Unripe group which was unfavorable for the induction cervix (n = 25). Samples were tested using untargeted metabolomics analysis and analyzed by a bioinformatics platform. The correlation analysis between the metabolome and the previously acquired microbiome was also performed. Results: A total of 629 metabolites were identified in cervicovaginal fluid. The cervicovaginal metabolome was significantly different between the women with the ripe cervix and those with the unripe cervix, especially within each stratum of the same CST. Metabolites within the amino acid, carbohydrate, and dipeptide pathways may play a role in this distinction. Thirty-four metabolites were significantly upregulated, and the remaining fourteen were significantly downregulated in the Unripe group with an unripe cervix unfavorable for induction. Statistical modeling identified Arachidonic Acid and Nicotinate associated with the risk of cervical maturation disorder (AUC 0.87) in negative ion mode. A combination of Choline and d-Mannose identified a risk of cervical maturation disorder (AUC 0.80) in positive ion mode, improved by Lactobacillus relative abundance (AUC 0.89). Conclusion: These data suggested that the cervicovaginal space was metabolically active during pregnancy and significantly altered among the women with the mature and immature cervix. Combining the genera-level phylotypes and metabolites could build better cervix maturity prediction models. By using cervicovaginal fluid samples, we demonstrated the potential of multi-data type integration for developing composite models toward understanding the contribution of the vaginal environment to the remodeling of cervix during term pregnancy.

This essay is not about the contemporary physics or philosophy of time, and it is not a direct contribution, so much as a prolegomenon, to serious dialogue between the Buddhist [...]