Human eye, skin and hair color pigmentation are highly heritable traits influenced by hundreds of genetic loci. The heritability and genetic etiology of the hyperpigmentation trait pregnancy-related linea nigra (PLN), where a dark but usually temporary vertical line develops on the abdomen, is unknown, and our understanding of its relationships with other pigmentation traits is limited. We conducted a genetic study of self-reported PLN in women of European ancestry, using a genome-based restricted maximum likelihood (GREML) method to estimate PLN heritability, performing a genomewide association study (GWAS) to explore the genetic factors underlying PLN, and calculating polygenic risk scores (PRS) to assess whether this trait shares genetic liability with two other skin pigmentation phenotypes, skin colour and mole count. We found 35% of the variance in developing PLN was explained by common genetic variation. The GWAS revealed four genomic loci suggestively associated (p values ≤ 1 × 10-6) with PLN: rs1263154 near the UPP2 gene (p = 9.0 × 10-7), rs26331 near SEMA6A (p = 6.6 × 10-7), rs78371540 in OLFM3 (p = 5.5 × 10-7), and rs72693263 near FLRT2 (p = 1.1 × 10-7). Of these genes only OLFM3 has been previously associated with pigmentation. Our PRS results provide the first evidence that genetic factors underlying skin color and mole count also contribute to the development of PLN in women of European ancestry.

Pulsar timing arrays (PTAs) are Galactic-scale nanohertz-frequency gravitational wave (GW) detectors. Recently, several PTAs have found evidence for the presence of GWs in their datasets, but none of them have achieved a community-defined definitive ($\gt 5\sigma$) detection. Here, we identify limiting noise sources for PTAs and quantify their impact on sensitivity to GWs under different observing and noise modelling strategies. First, we search for intrinsic pulse jitter in a sample of 89 millisecond pulsars (MSPs) observed by the MeerKAT Pulsar Timing Array (MPTA) and obtain new jitter measurements for 20 MSPs. We then forecast jitter noise in pulsars for the future SKA-Mid telescope, finding that the timing precision of many of the best-timed MSPs would be dominated by jitter noise. We then consider dispersion measure variations from the interstellar medium and find that their effects are best mitigated by modelling them as a stationary Gaussian process with a power law spectrum. Improving upon the established hasasia code for PTA sensitivity analysis, we assess the timing potential of the lower frequency UHF-band (544$-$1088 MHz) of MeerKAT and find a potential increase in GW background sensitivity by $\approx 8$%, relative to observing at L-band. We show that this improvement relies on assumptions on the propagation through the interstellar medium and highlight that if observing frequency-dependent propagation effects, such as scattering noise, are present, where noise is not completely correlated across observing frequency, then the improvement is significantly diminished. Using the multi-frequency receivers and sub-arraying flexibility of MeerKAT, we find that focused, high-cadence observations of the best MSPs can enhance the sensitivity of the array for both the continuous GWs and stochastic GW background. These results highlight the role of MeerKAT and the MPTA in the context of international GW search efforts.

Many important decisions, for example, applying to college, require an individual to simultaneously submit several applications. These decisions are unique as each application is risky because acceptance is uncertain while also being rival as one can only attend a single college. In an influential theoretical analysis of these problems, Chade and Smith (2006) establish the No Safety Schools Theorem which suggests larger portfolios are riskier than single choices. We offer experimental evidence, using several experiments, that this theorem is routinely violated. In fact, the majority of our subjects violate this theorem. However, performance improves with practice, advice, and feedback.

Background: Multidrug-resistant organisms (MDRO), including those producing extended-spectrum beta lactamases (ESBL) are increasing. Infections, especially with MDRO, lead to increased healthcare costs. Bloodstream infections (BSI) caused by ESBL-producing Klebsiella pneumoniae increased at our institution in 2021-2022. An assessment as to whether these organisms were acquired during hospitalization or other healthcare exposures was conducted. Methods: The rates of ESBL-producing Klebsiella BSI per 1000 hospitalizations in 2021 and 2022 in transplant recipients and non-transplant patients were compared. From 1/1/2021 to 06/30/2023, 49 adult patients at an academic medical center had Klebsiella pneumoniae BSI with ceftriaxone resistance and a high probability of carrying an ESBL. Of these, 20 were transplant recipients and 29 were non-transplant patients. We performed whole-genome sequencing on the 28 available unique patient isolates (12 transplant; 16 non-transplant) to assess relatedness. Additional data were collected by chart review on transplant recipients. BugSeq bioinformatics pipeline and refMLST were utilized on the sequenced isolates to assess clonality, defined as ≤20 allele difference between two isolates. Results: The rate of ESBL-producing Klebsiella BSI increased universally from 2021 to 2022 but impacted the transplant cohort (0.3 to 3.6 per 1000 hospitalizations) more than the non-transplant cohort (0.2 to 0.5 per 1000 hospitalizations). Kidney and liver transplants were most often involved (5 out of 49 patients each). In the transplant cohort, bacteremia alone (45%, 9 out of 20) and urinary source (35%, 7 out of 20) were the most frequently identified etiologies. The most common sequence type was ST-307, accounting for 64% of total sequenced isolates (67% of transplant; 63% of non-transplant). The most common ESBL gene identified was blaCTX-M-15, identified in 24 isolates (86%). Less common resistance genes included blaSHV-12 (N=3) and blaCTX-M-3 (N=1). While there were 5 isolates within 20 allele differences (3 transplant; 2 non-transplant), they were separated in time and did not have obvious epidemiologic connections. While there was a change in TMP-SMX prophylaxis protocol during this time in kidney transplant recipients, it did not explain the increase observed in other transplant groups. Conclusions: There was a sharp increase in the number of BSI caused by ESBL-producing Klebsiella pneumoniae in the transplant population between 2021 and 2022. A molecular epidemiologic analysis ruled out clonal transmission from breakdown of infection prevention practices as the cause. No other common epidemiologic link was identified. This demonstrates the application of whole-genome sequencing in excluding a clonal outbreak from a common source within an institution.

Background: Data in adults and older children demonstrate repeat blood cultures (BlCx) are not always necessary. Indications for repeat BlCx include Staphylococcus aureus or yeast in the initial blood culture, or the presence of a central venous catheter (CVC). Blood collection in premature babies can be challenging and there are little data regarding when repeat BlCxs are necessary after an initial positive. The goal of this study is to determine risk factors for persistent bloodstream infection (BSI) to determine when unnecessary blood cultures can be avoided. Methods: The Yale New Haven Children’s Hospital NNICU is a 68-bed level 4 unit. Babies in the NNICU with a positive blood culture from 8/1/16 to 12/31/21 were included. Persistent BSI was defined as a repeat positive BlCx with the same organism >48 hrs. after the original culture. A BlCx > 7 days after the original BlCx was considered a new event. Babies who died within 48 hrs. of the initial culture were excluded. In preliminary analysis we did not distinguish between true BSI and contamination. Data were extracted from the medical record by the Yale Data Analytics Team and by manual chart review. Data were stored in excel for descriptive statistics. Additional statistical analysis in SPSS is on-going to account for multiple variables. Results: 142 babies had a positive BlCx with 122 babies alive at 48 hrs. and included in the study. These 124 babies had 139 positive BlCx growing 145 organisms. Persistent BSI occurred in 17.3% (24/139) of BlCxs. Factors associated with persistence in univariate analyses included the presence of a CVC and recovery of S. aureus. (Table 1) No babies with either streptococcal infection or early onset sepsis had persistent BSI. (Table 1) Additional variables under evaluation in a multiple regression model to determine the probability of persistent BSI include other sources of infection, white blood cell count at the time of BlCx, congenital heart disease, immunosuppressive agents such as steroids and whether empiric antibiotic therapy was appropriate. We will also define probable contaminants and repeat the analyses with and without these BSI episodes. Conclusions: Preliminary analysis shows that neonates have similar risk factors for persistent BSI as adults including the presence of a CVC and the recovery of S. aureus that require repeat BlCx to confirm clearance. For babies with streptococcal infection, repeat BlCx may not be routinely required. Current work is examining additional potential risk factors in multi-variable models.

Background: A Quality Improvement (QI) initiative to reduce invasive Staphylococcus aureus (SA) infections in a level IV neonatal intensive care unit (NICU) successfully eliminated Methicillin-resistant (MRSA) but not Methicillin-susceptible (MSSA) infections. A combination of SA whole genome sequencing (WGS) and environmental culturing helped to better understand the epidemiology of MSSA colonization and infection in the NICU and drive new infection prevention interventions. Methods: Environmental surveillance of high-touchpoint surfaces for SA was performed using Dey and Engley neutralizing agar. Selected isolates were confirmed as SA using Columbia Sheep’s Blood agar and Staphaurex testing. Statistical analyses examined correlations between monthly effective cleaning, hand hygiene compliance, and colonization rates. To better understand MSSA spread in the NICU, WGS was performed on a convenience sample of 42 MSSA isolates, sampled one month before and after an invasive MSSA infection. Data extracted from electronic health records were used for retrospective room tracing of colonized patients with related isolates to determine modes of transmission. Results: WGS analysis MSSA isolates revealed four MSSA strains from 29 patients suggesting within unit transmission, while 13 patients were colonized with unique MSSA isolates suggesting external sources. Retrospective room tracing of colonized patients identified three transmission patterns: subsequent room occupant transmission, intra-pod spread, and inter-pod transmission without patient transfer, with evidence that these strains were endemic within the unit for at least 3-12 months. Statistical analyses showed no significant correlation between environmental cleaning or hand hygiene compliance and colonization rates. Conclusions: Persistent MSSA colonization and invasive infections in the NICU result from both within-unit transmission and the introduction of unique isolates. These findings are being used to inform the development of new interventions, including updated below-the-elbow hand hygiene protocols, revised environmental cleaning plans, nurse-parent communication training, and a virtual reality hand hygiene training program for parents and staff. WGS of pathogenic organisms is a useful tool to drive QI initiatives aimed at reducing hospital-acquired infections.

Over the past decade, several multi-institutional research consortia have formed within the North American pediatric surgical community. In this article, we describe our experience with the creation and implementation of the Eastern Pediatric Surgery Network, a large and comprehensive research consortium designed to produce a wide array of high-quality clinical studies within our subspecialty. In 2020, a vision statement and rules of governance were established at thirteen academic pediatric surgery divisions in the eastern United States. The research consortium was organized based on four major pillars, namely legal ownership of aggregate data, horizontal leadership structure, mandatory participation in adopted studies, and a broad research portfolio that encompasses the full breath of the specialty. Over the past five years, the number of research projects has dramatically expanded over time and includes participation from 24 different medical centers. Despite a lack of dedicated sponsored extramural support for most projects, there have been 28 abstracts presented at national conferences and 12 manuscripts published in peer-reviewed journals. It is our hope that sharing our experience with creating this organization can help to inform others interested in establishing the academic infrastructure to engage in multi-institutional, evidence-based clinical research in other medical specialties and beyond.

In Antimicrobial Stewardship and Infection Prevention and Control, programmatic goals often strive to achieve clinical benefit by practice change in the direction of doing less. Practically, this may include reducing the number of tests ordered, encouraging shorter and more narrow courses of antimicrobials, or discontinuing practices that are no longer contextually appropriate. Because promoting practice change in the direction of doing less is a critical aspect of day-to-day operations in Antimicrobial Stewardship and Infection Prevention and Control, the goals of this Society for Healthcare Epidemiology Research Committee White Paper are to provide a roadmap and framework for leveraging principles of implementation and de-implementation science in day-to-day practice. Part II of this series focuses on some practical case studies, including real-world examples of applied de-implementation science to promote discontinuation of practices that are ineffective, overused, or no longer effective.

Newgrange, the Neolithic monument and centerpiece of the Brú na Bóinne UNESCO World Heritage complex, is a high-profile example of prehistoric societies’ observation of, and reverence for, solar events. Comparatively little is known about how these concepts were remembered by those using Newgrange over subsequent millennia. While excavations have uncovered large quantities of later material culture, debate continues about what these subsequent activities represent. We combine zooarchaeological, radiocarbon, and isotopic evidence to assess the nature and seasonality of human–animal–environment relationships at Newgrange. Results show a concentration of feasting activity, focused on pigs, dating to 2600–2450 BC and indicate that most pigs were slaughtered shortly after a period of rapid, pannage-fueled weight gain. This seasonal specificity indicates feasting likely occurred in the weeks around the winter solstice and suggests that, centuries after passage tomb construction ended, practices at Newgrange continued to focus on the general winter solstice timeframe. We also connect a unique isotopic signature for mast (tree nuts) with pannage husbandry, a pattern that should allow for reinterpretation of archaeological pig diets and human–woodland relationships across Europe.

Pension systems play a crucial role in providing economic security and supporting well-being in later life. However, as governments implement reforms to ensure financial sustainability—such as raising the retirement age, reducing benefits, and shifting to defined-contribution schemes—these measures often overlook their psychological and social consequences. Pension insecurity has been linked to heightened stress, anxiety, and depression, as well as increased social isolation, particularly among vulnerable populations, including those in physically demanding jobs, low-income workers, and individuals with existing health conditions. Despite clear evidence of these effects, mainstream pension reform discourse prioritises fiscal concerns over social and mental health implications. This article examines pension reform through the Human Rights–Public Health Pension Framework (HRPHPF), integrating legal, public health, and policy perspectives to assess its impact on mental well-being. It situates pension rights within international human rights law, explores the psychological risks associated with pension insecurity, and advocates for a human rights-based approach to pension policymaking. The article calls for integrating mental health impact assessments into pension reforms to prevent adverse outcomes and ensure that policies promote dignity, social inclusion, and economic security in old age. A more balanced approach is necessary to align financial sustainability with broader well-being and human rights principles.

The savannah–forest mosaic of the Rupununi region of Guyana is a dispersal corridor between large tracts of intact Guiana Shield forests and a subsistence hunting ground for Indigenous Makushi and Wapichan communities. We conducted a camera-trap survey at 199 sites across four major forested habitat types and used multi-species occupancy modelling to determine regional-scale drivers of mammalian occupancy at both species and community levels, accounting for imperfect detection. We detected 47 savannah- and forest-dwelling mammal species, with the occupancy of medium- and large-bodied terrestrial mammal species (community occupancy) positively related to per cent forest cover and negatively to the presence of gallery forest habitat. The occupancy of 15 of 30 species was positively related to forest cover, suggesting the importance of maintaining forested habitat within the broader mosaic comprising savannahs and intermediate habitats for sustaining maximum mammal diversity. Jaguar Panthera onca occupancy was associated with the presence of livestock, and giant anteater Myrmecophaga tridactyla occupancy was negatively associated with distance to the nearest road, both results of concern in relation to potential human–wildlife conflict. The probability of detecting terrestrial mammal species (community detectability) increased away from villages, as did the detectability of two large-bodied, hunted species, the lowland tapir Tapirus terrestris and collared peccary Pecari tajacu, potentially indicating the negative effects of subsistence and commercial hunting in this savannah mosaic habitat. We use our findings to discuss how management strategies for hunting, fire, timber harvest and agriculture within Indigenous titled lands could help ensure the sustainability of these traditional livelihood activities.