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Abstract The diagnosis of prostate cancer using histopathology is reliant on the accurate interpretation of prostate tissue sections. Current standards rely on the assessment of Haematoxylin and Eosin (H&E) staining, which can be difficult to interpret and introduce inter-observer variability. Here, we present a digital pathology atlas and online resource of prostate cancer tissue micrographs for both H&E and the reinterpretation of samples using a novel set of three biomarkers as an interactive tool, where clinicians and scientists can explore high resolution histopathology from various case studies. The digital pathology prostate cancer atlas when used in conjunction with the biomarkers, will assist pathologists to accurately grade prostate cancer tissue samples.

Abstract Background Hospitals in any given region can be considered as part of a network, where facilities are connected to one another – and hospital pathogens potentially spread – through the movement of patients between them. We sought to describe the hospital admission patterns of patients known to be colonised with carbapenemase-producing Enterobacterales (CPE), and compare them with CPE-negative patient cohorts, matched on comorbidity information. Methods We performed a linkage study in Victoria, Australia, including datasets with notifiable diseases (CPE notifications) and hospital admissions (admission dates and diagnostic codes) for the period 2011 to 2020. Where the CPE notification date occurred during a hospital admission for the same patient, we identified this as the ‘index admission’. We determined the number of distinct health services each patient was admitted to, and time to first admission to a different health service. We compared CPE-positive patients with four cohorts of CPE-negative patients, sampled based on different matching criteria. Results Of 528 unique patients who had CPE detected during a hospital admission, 222 (42%) were subsequently admitted to a different health service during the study period. Among these patients, CPE diagnosis tended to occur during admission to a metropolitan public hospital (86%, 190/222), whereas there was a greater number of metropolitan private (23%, 52/222) and rural public (18%, 39/222) hospitals for the subsequent admission. Median time to next admission was 4 days (IQR, 0–75 days). Admission patterns for CPE-positive patients was similar to the cohort of CPE-negative patients matched on index admission, time period, and age-adjusted Charlson comorbidity index. Conclusions Movement of CPE-positive patients between health services is not a rare event. While the most common movement is from one public metropolitan health service to another, there is also a trend for movement from metropolitan public hospitals into private and rural hospitals. After accounting for clinical comorbidities, CPE colonisation status does not appear to impact on hospital admission frequency or timing. These findings support the potential utility of a centralised notification and outbreak management system for CPE positive patients.

Introduction Thailand was one of the first low- and middle-income countries to publicly fund seasonal influenza vaccines, but the lack of predictability in the timing of epidemics and difficulty in predicting the dominant influenza subtypes present a challenge for existing vaccines. Next-generation influenza vaccines (NGIVs) are being developed with the dual aims of broadening the strain coverage and conferring longer-lasting immunity. However, there are no economic evaluations of NGIVs in Thailand.Methods We estimated the health impact and cost-effectiveness of NGIVs in Thailand between 2005 and 2009 using a combined epidemiological and economic model. We fitted the model to data on laboratory-confirmed influenza cases and then simulated the number of influenza infections, symptomatic cases, hospitalisations and deaths under different vaccination scenarios based on WHO-preferred product characteristics for NGIVs. We used previous estimates of costs and disability adjusted life years (DALYs) for influenza health outcomes to estimate incremental net monetary benefit, vaccine threshold prices and budget impact.Results With the current vaccine programme, there were an estimated 61 million influenza infections. Increasing coverage to 50% using improved vaccines reduced infections to between 23 and 57 million, and with universal vaccines to between 21 and 49 million, depending on the age groups targeted. Depending on the comparator, threshold prices for NGIVs ranged from US$2.80 to US$12.90 per dose for minimally improved vaccines and US$24.60 to US$69.90 for universal vaccines.Conclusion Influenza immunisation programmes using NGIVs are anticipated to provide considerable health benefits and be cost-effective in Thailand. However, although NGIVs might even be cost-saving in the long run, there could be significant budget implications for the Thai government even if the vaccines can be procured at a substantial discount to the maximum threshold price.

Objective: To investigate what overweight or obese adults with prediabetes in the United States report being told by providers about 1) having prediabetes, 2) diabetes risk, and 3) losing weight and the associations of these communications with attempted weight loss. Methods: Data from 2015 to 2018 National Health and Nutrition Examination Surveys (NHANES) for adults with a body mass index in the overweight or obesity ranges and HbA1c in the prediabetes range were examined (n = 2085). Patient reported data on what providers told them about having prediabetes, being at risk for diabetes, and losing weight were compared with attempted weight loss. Results: Most participants (66.4%) reported never being told they had prediabetes nor being at risk for diabetes, 13.0% reported being told they had prediabetes, 10.6% at risk for diabetes, and 8.0% both messages. 18.3% of participants reported being told to lose weight. Participants who reported being told they had prediabetes and at increased diabetes risk were more likely to report attempted weight loss (adjusted odds ratio (AOR) 1.8, 95% confidence interval (CI) 1.1–3.2). Reporting that they were told to lose weight was not significantly associated with an increase in reported weight loss attempts. Conclusions: In this cohort of individuals with overweight/obesity and prediabetic HbA1c values, low rates communications with providers about prediabetes and diabetes risk were reported. When both were discussed, patients reported greater attempted weight loss. These findings draw attention to the potential impact that provider communications about prediabetes and diabetes risk may have on lifestyle behavior change.

BackgroundThe number of individuals using digital health devices has grown in recent years. A higher rate of use in patients suggests that primary care providers (PCPs) may be able to leverage these tools to effectively guide and monitor physical activity (PA) for their patients. Despite evidence that remote patient monitoring (RPM) may enhance obesity interventions, few primary care practices have implemented programs that use commercial digital health tools to promote health or reduce complications of the disease. ObjectiveThis formative study aimed to assess the perceptions, needs, and challenges of implementation of an electronic health record (EHR)–integrated RPM program using wearable devices to promote patient PA at a large urban primary care practice to prepare for future intervention. MethodsOur team identified existing workflows to upload wearable data to the EHR (Epic Systems), which included direct Fitbit (Google) integration that allowed for patient PA data to be uploaded to the EHR. We identified pictorial job aids describing the clinical workflow to PCPs. We then performed semistructured interviews with PCPs (n=10) and patients with obesity (n=8) at a large urban primary care clinic regarding their preferences and barriers to the program. We presented previously developed pictorial aids with instructions for (1) providers to complete an order set, set step-count goals, and receive feedback and (2) patients to set up their wearable devices and connect them to their patient portal account. We used rapid qualitative analysis during and after the interviews to code and develop key themes for both patients and providers that addressed our research objective. ResultsIn total, 3 themes were identified from provider interviews: (1) providers’ knowledge of PA prescription is focused on general guidelines with limited knowledge on how to tailor guidance to patients, (2) providers were open to receiving PA data but were worried about being overburdened by additional patient data, and (3) providers were concerned about patients being able to equitably access and participate in digital health interventions. In addition, 3 themes were also identified from patient interviews: (1) patients received limited or nonspecific guidance regarding PA from providers and other resources, (2) patients want to share exercise metrics with the health care team and receive tailored PA guidance at regular intervals, and (3) patients need written resources to support setting up an RPM program with access to live assistance on an as-needed basis. ConclusionsImplementation of an EHR-based RPM program and associated workflow is acceptable to PCPs and patients but will require attention to provider concerns of added burdensome patient data and patient concerns of receiving tailored PA guidance. Our ongoing work will pilot the RPM program and evaluate feasibility and acceptability within a primary care setting.

Background: Obesity increases risk of atrial fibrillation (AF) at least in part due to pro-inflammatory effects, but has been paradoxically associated with improved mortality. Although statins have pleiotropic anti-inflammatory properties, their interaction with obesity and clinical outcomes in AF is unknown. We explored the relationship between BMI, statin use, and all-cause mortality and AF/congestive heart failure (CHF)-related encounters, hypothesizing that statin exposure may be differentially associated with improved outcomes in overweight/obesity. Methods: This was a single center retrospective cohort study of adults with AF diagnosed between 2011–2018. Patients were grouped by body mass index (BMI) and statin use at time of AF diagnosis. Outcomes included all-cause mortality and ED or inpatient encounters for AF or CHF. Results and Conclusions: A total of 2503 subjects were included (median age 66 years, 43.4 % female, median BMI 29.8 kg/m2, 54.6 % on baseline statin therapy). Increasing BMI was associated with decreased mortality hazard but not associated with AF/CHF encounter risk. Adjusting for statin-BMI interaction, demographics, and cardiovascular comorbidities, overweight non-statin users experienced improved mortality (adjusted hazard ratio [aHR] 0.55, 95 % CI 0.35–0.84) compared to statin users (aHR 0.98, 95 % CI 0.69–1.40; interaction P-value = 0.013). Mortality hazard was consistently lower in obese non-statin users than in statin users, however interaction was insignificant. No significant BMI-statin interactions were observed in AF/CHF encounter risk. In summary, statin use was not differentially associated with improved mortality or hospitalization risk in overweight/obese groups. These findings do not support statins for secondary prevention of adverse outcomes based on overweight/obesity status alone.

Background:. Cosmetic plastic surgery in the United States is underutilized by African American and Hispanic populations compared with their White and Asian counterparts. This study evaluated whether microeconomic spending traits as a representation of financial stability can inform trends in cosmetic procedure volumes by racial group. Methods:. Annual volumes for the top five cosmetic surgical and cosmetic minimally invasive procedures by racial/ethnic group from 2012 to 2020 were collected from the American Society of Plastic Surgeons’ annual reports. Factor analysis was used to calculate inflexible and flexible consumer spending by racial/ethnic groupings from the US Bureau of Labor Statistics’ consumer expenditure data. All four factors were calculated across US Bureau of Labor Statistics–defined racial/ethnic groupings and standardized so they could be interpreted relative to each other. Results:. Compared with the other groupings, the White/Asian/other grouping spent significantly more on average for inflexible consumer spending (P = 0.0097), flexible consumer spending (P < 0.0001), cosmetic surgical procedures (P < 0.0001), and cosmetic minimally invasive procedures (P = 0.0006). In contrast, African American people spent significantly less on average for all four factors (all P < 0.01). For Hispanic people, values were significantly less on average for flexible consumer spending (P = 0.0023), cosmetic surgical procedures (P < 0.0001), and cosmetic minimally invasive procedures (P = 0.0002). Conclusions:. This study demonstrates that inflexible and flexible consumer spending follow trends in utilization of cosmetic surgical and minimally invasive procedures by racial/ethnic groups. These microeconomic spending inequities may help further contextualize the racial/ethnic variation in access to cosmetic surgery.

Background Antibiotic usage, contact with high transmission healthcare settings as well as changes in immune system function all vary by a patient's age and sex. Yet, most analyses of antimicrobial resistance (AMR) ignore demographic indicators and provide only country-level resistance prevalence values. This study aimed to address this knowledge gap by quantifying how resistance prevalence and incidence of bloodstream infection (BSI) varied by age and sex across bacteria and antibiotics in Europe. Methods and findings We used patient-level data collected as part of routine surveillance between 2015 and 2019 on BSIs in 29 European countries from the European Antimicrobial Resistance Surveillance Network (EARS-Net). A total of 6,862,577 susceptibility results from isolates with age, sex, and spatial information from 944,520 individuals were used to characterise resistance prevalence patterns for 38 different bacterial species and antibiotic combinations, and 47% of these susceptibility results were from females, with a similar age distribution in both sexes (mean of 66 years old). A total of 349,448 isolates from 2019 with age and sex metadata were used to calculate incidence. We fit Bayesian multilevel regression models by country, laboratory code, sex, age, and year of sample to quantify resistant prevalence and provide estimates of country-, bacteria-, and drug-family effect variation. We explore our results in greater depths for 2 of the most clinically important bacteria-antibiotic combinations (aminopenicillin resistance in Escherichia coli and methicillin resistance in Staphylococcus aureus) and present a simplifying indicative index of the difference in predicted resistance between old (aged 100) and young (aged 1). At the European level, we find distinct patterns in resistance prevalence by age. Trends often vary more within an antibiotic family, such as fluroquinolones, than within a bacterial species, such as Pseudomonas aeruginosa. Clear resistance increases by age for methicillin-resistant Staphylococcus aureus (MRSA) contrast with a peak in resistance to several antibiotics at approximately 30 years of age for P. aeruginosa. For most bacterial species, there was a u-shaped pattern of infection incidence with age, which was higher in males. An important exception was E. coli, for which there was an elevated incidence in females between the ages of 15 and 40. At the country-level, subnational differences account for a large amount of resistance variation (approximately 38%), and there are a range of functional forms for the associations between age and resistance prevalence. For MRSA, age trends were mostly positive, with 72% (n = 21) of countries seeing an increased resistance between males aged 1 and 100 years and a greater change in resistance in males. This compares to age trends for aminopenicillin resistance in E. coli which were mostly negative (males: 93% (n = 27) of countries see decreased resistance between those aged 1 and 100 years) with a smaller change in resistance in females. A change in resistance prevalence between those aged 1 and 100 years ranged up to 0.51 (median, 95% quantile of model simulated prevalence using posterior parameter ranges 0.48, 0.55 in males) for MRSA in one country but varied between 0.16 (95% quantile 0.12, 0.21 in females) to -0.27 (95% quantile -0.4, -0.15 in males) across individual countries for aminopenicillin resistance in E. coli. Limitations include potential bias due to the nature of routine surveillance and dependency of results on model structure. Conclusions In this study, we found that the prevalence of resistance in BSIs in Europe varies substantially by bacteria and antibiotic over the age and sex of the patient shedding new light on gaps in our understanding of AMR epidemiology. Future work is needed to determine the drivers of these associations in order to more effectively target transmission and antibiotic stewardship interventions., Author(s): Naomi R. Waterlow 1, Ben S. Cooper 2, Julie V. Robotham 3, Gwenan Mary Knight 1,4,* Introduction Antimicrobial resistance (AMR) is a global public health priority [1]. Understanding how [...]

Summary:. Although research and innovation is a key within the field of plastic and reconstructive surgery, the impact of team structure, interpersonal dynamics, and/or standardized infrastructure on scholarly output has been infrequently studied. In this work, we present the formation and implementation of a novel plastic surgery research program that aims to unite previously disparate clinical and translational research efforts at our institution to facilitate critical inquiry. From July 2022 to June 2023, our department launched a pilot research program based on three pillars: (1) formalization of a research curriculum (monthly research meetings for agenda setting and discussion for project honing, formal research leadership for meeting facilitation and workflow regulation), (2) development of a centralized database to compile ongoing research (Google Drive repository to house all ongoing research documents, facilitate real-time editing, and provide resources/templates for assisting in the research process), and (3) bolstering of a core research identity built on mentorship and collaboration (more frequent interactions to shift previously siloed faculty-student mentorship into a robust milieu of intercollaboration). During the first year, we saw an increased number of publications and presentations, as well as robust participation and contribution from faculty, residents, and medical students. Future directions will focus on addressing resource limitation, such as project idea availability and funding, to sustain the success and growth of this novel research infrastructure.

Abstract Sea‐level rise is leading to increasingly frequent coastal floods globally. Recent research shows that changes in tidal properties and storm surge magnitudes can further exacerbate sea‐level rise‐related increases in flood frequencies. However, such non‐stationarity in tide and storm surge statistics are largely neglected in existing coastal flood projection methodologies. Here we develop a framework to explore the effect that different realizations of various sources of uncertainty have on projections of coastal flood frequencies, including changes in tidal range and storminess. Our projection methodology captures how observed flood rates depend on how storm surges coincide with tidal extremes. We show that higher flood rates and earlier emergence of chronic flooding are associated with larger sea‐level rise rates, lower flood thresholds, and increases in tidal range and skew surge magnitudes. Smaller sea‐level rise rates, higher flood thresholds and decreases in sea level variability lead to commensurately lower flood rates. Percentagewise, changes in tidal amplitudes generally have a much larger impact on flood frequencies than equivalent percentagewise changes in storm surge magnitudes. We explore several implications of these findings. Firstly, understanding future local changes in storm surges and tides is required to fully quantify future flood hazards. Secondly, existing hazard assessments may underestimate future flood rates as changes in tides are not considered. Finally, identifying the flood frequencies and severities relevant to local coastal managers is imperative to develop useable and policy‐relevant projections for decisionmakers.

Tidal flooding occurs when coastal water levels exceed impact-based flood thresholds due to tides alone, under average weather conditions. Transitions to tidal flood regimes are already underway for nuisance flood severities in harbours and bays and expected for higher severities in coming decades. In the first such regional assessment, we show that the same transition to tidally forced floods can also be expected to occur in Australian estuaries with less than 0.1 m further sea-level rise. Flood thresholds that historically used to only be exceeded under the combined effects of riverine (freshwater) and coastal (salt water) influences will then occur due to high tides alone. Once this tidal flooding emerges, it is projected to become chronic within two decades. Locations most at-risk of the emergence of tidal flooding and subsequent establishment of chronic flood regimes are those just inside estuary entrances. These locations are exemplified by low freeboard, the vertical distance between a flood threshold and a typical high tide level. We use a freeboard-based analysis to estimate the sea-level rise required for impacts associated with official flood thresholds to occur due to tides alone. The resultant tide-only flood frequency estimates provide a lower bound for future flood rates.

Background: According to the World Health Organization (WHO), healthy aging is the process of developing and maintaining the functional capacity for health in old age. A rapidly growing number of research studies on healthy aging have been conducted worldwide. The purpose of this research work is to explore global scientific landscape of healthy aging research over the last 22 years. Methods: Scientific publications on healthy aging from January 1, 2000 to October 11, 2022 were retrieved from the Web of Science Core Collection (WoSCC) on October 11, 2022. A total of 6420 publications were included in the scientometric analysis. VOSviewer (1.6.18) was used to conduct scientometric and visualized analysis. Results: The publication growth rate was 35.68 from 2000 to 2021. The United States of America (USA) led in both productivity and citations. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA was prominent in terms of both the highest citation count and the highest average citation count. The National Institute on Aging (NIA) and Evans, Michele K. were the most influential organization and author, respectively. Research hotspots in healthy aging were identified based on the co-occurrence analysis of keywords: (1) physical activity and mental health of older adults; (2) diseases impacting the health and lifespan of older adults; and (3) neuroscience. Our analysis indicates that gut microbiota, loneliness, frailty, mitochondria and resilience were the emerging themes in healthy aging research. Conclusions: The quantity of annual publications on healthy aging has rapidly increased over the past 22 years, especially during 2018–2021. This analysis identified the status, trends, hot topics, and frontiers of healthy aging research. These findings will help researchers quickly understand the global representation of healthy aging research, influence resource dissemination, promote international collaborations, guide policy formulation, and improve health services for older adults.

This study investigates the determinants of trading activity in the U.S. corporate bond market, focusing on the effects of Seasonal Affective Disorder (SAD) and macroeconomic announcements. Employing the General-to-Specific (Gets) Autometrics methodology, we identify distinct behavioral responses between retail and institutional investors to SAD, noting a significant impact on retail trading volumes but not on institutional trading or bond returns. This discovery extends the understanding of behavioral finance within the context of bond markets, diverging from established findings in equity and Treasury markets. Additionally, our analysis delineates the influence of macroeconomic announcements on trading activities, offering new insights into the market’s reaction to economic news. This study’s findings contribute to the broader literature on market microstructure and behavioral finance, providing empirical evidence on the interplay between psychological factors and macroeconomic information flow within corporate bond markets. By addressing these specific aspects with rigorous econometric techniques, our research enhances the comprehension of trading dynamics in less transparent markets, offering valuable perspectives for academics, investors, risk managers, and policymakers.

Models of the resolved Event Horizon Telescope (EHT) sources Sgr A* and M87* are constrained by observations at multiple wavelengths, resolutions, polarizations, and time cadences. In this paper, we compare unresolved circular polarization (CP) measurements to a library of models, where each model is characterized by a distribution of CP over time. In the library, we vary the spin of the black hole, the magnetic field strength at the horizon (i.e., both SANE and magnetically arrested disk or MAD models), the observer inclination, a parameter for the maximum ion–electron temperature ratio assuming a thermal plasma, and the direction of the magnetic field dipole moment. We find that Atacama Large Millimeter/submillimeter Array (ALMA) observations of Sgr A* are inconsistent with all edge-on ( i = 90°) models. Restricting attention to the MAD models favored by earlier EHT studies of Sgr A*, we find that only models with magnetic dipole moment pointing away from the observer are consistent with ALMA data. We also note that in 26 of the 27 passing MAD models, the accretion flow rotates clockwise on the sky. We provide a table of the means and standard deviations of the CP distributions for all model parameters, along with their trends.

The 230 GHz lightcurves of Sagittarius A* (Sgr A*) predicted by general relativistic magnetohydrodynamics and general relativistic ray-tracing (GRRT) models by the Event Horizon Telescope Collaboration have higher variability M _Δ _T compared to observations. In this series of papers, we explore the origin of such large brightness variability. In this first paper, we performed large GRRT parameter surveys that span from the optically thin to the optically thick regimes, covering the ion-to-electron temperature ratio under strongly magnetized conditions, R _Low , from 1 to 60. We find that increasing R _Low can lead to either an increase or a reduction in M _Δ _T depending on the other model parameters, making it consistent with the observed variability of Sgr A* in some cases. Our analysis of GRRT image snapshots finds that the major contribution to the large M _Δ _T for the R _Low = 1 models comes from the photon ring. However, secondary contributions from the accretion flow are also visible depending on the spin parameter. Our work demonstrates the importance of the electron temperature used for modeling radiatively inefficient accretion flows and places new constraints on the ion-to-electron temperature ratio. A more in-depth analysis for understanding the dependencies of M _Δ _T on R _Low will be performed in subsequent papers.

Movement is a key means by which animals cope with variable environments. As they move, animals construct individual niches composed of the environmental conditions they experience. Niche axes may vary over time and covary with one another as animals make tradeoffs between competing needs. Seasonal migration is expected to produce substantial niche variation as animals move to keep pace with major life history phases and fluctuations in environmental conditions. Here, we apply a time-ordered principal component analysis to examine dynamic niche variance and covariance across the annual cycle for four species of migratory crane: common crane (Grus grus, n = 20), demoiselle crane (Anthropoides virgo, n = 66), black-necked crane (Grus nigricollis, n = 9), and white-naped crane (Grus vipio, n = 9). We consider four key niche components known to be important to aspects of crane natural history: enhanced vegetation index (resources availability), temperature (thermoregulation), crop proportion (preferred foraging habitat), and proximity to water (predator avoidance). All species showed a primary seasonal niche "rhythm" that dominated variance in niche components across the annual cycle. Secondary rhythms were linked to major species-specific life history phases (migration, breeding, and nonbreeding) as well as seasonal environmental patterns. Furthermore, we found that cranes' experiences of the environment emerge from time-dynamic tradeoffs among niche components. We suggest that our approach to estimating the environmental niche as a multidimensional and time-dynamical system of tradeoffs improves mechanistic understanding of organism-environment interactions. [ABSTRACT FROM AUTHOR]

This paper focuses on developing a reduction-based algebraic multigrid (AMG) method that is suitable for solving general (non)symmetric linear systems and is naturally robust from pure advection to pure diffusion. Initial motivation comes from a new reduction-based AMG approach, ℓAIR (local approximate ideal restriction), that was developed for solving advection-dominated problems. Though this new solver is very effective in the advection-dominated regime, its performance degrades in cases where diffusion becomes dominant. This is consistent with the fact that in general, reduction-based AMG methods tend to suffer from growth in complexity and/or convergence rates as the problem size is increased, especially for diffusion-dominated problems in two or three dimensions. Motivated by the success of ℓAIR in the advective regime, our aim in this paper is to generalize the AIR framework with the goal of improving the performance of the solver in diffusion-dominated regimes. To do so, we propose a novel way to combine mode constraints as used commonly in energy-minimization AMG methods with the local approximation of ideal operators used in ℓAIR. The resulting constrained ℓAIR algorithm is able to achieve fast scalable convergence on advective and diffusive problems. In addition, it is able to achieve standard low complexity hierarchies in the diffusive regime through aggressive coarsening, something that was previously difficult for reduction-based methods. [ABSTRACT FROM AUTHOR]