Are lateralized and bold fish optimistic or pessimistic?

Cognitive bias is defined as the influence of emotions on cognitive processes. The concept of the cognitive judgement bias has its origins in human psychology but has been applied to animals over the past 2 decades. In this study we were interested in determining if laterality and personality traits, which are known to influence learning style, might also be correlated with a cognitive bias in the three-spined sticklebacks (Gasterosteus aculeatus). We used the judgement bias test with the go/no-go procedure where fish were first trained to discriminate between a black and white card and, after reaching a minimum learning criterion, tested their response to an ambiguous card (grey). Optimistic subjects were expected to have a high expectation of reward associated with an ambiguous stimulus, whereas pessimistic subjects a high expectation of non-reward. We used an emergence and a mirror test to quantify boldness and laterality, respectively. We hypothesised that male, bolder and more strongly lateralized fish would be more optimistic than female, shy and less strongly lateralised fish. We found that males and more strongly lateralized fish were more optimistic than females and less strongly lateralized fish. In addition, bold males were more optimistic than shy males as we predicted, but females showed the opposite pattern. Finally, fish trained on the black colour card learned the training task faster than those trained on a white card. Our results indicate that both laterality and personality traits are linked to animals' internal states (pessimistic or optimistic outlooks) which likely has broad implications for understanding animal behaviour particularly in a welfare context.

Overdose deaths before and during the COVID-19 pandemic in a US county.

Introduction: Globally, overdose deaths increased near the beginning of the COVID-19 pandemic, which created availability and access barriers to addiction and social services. Especially in times of a crisis like a pandemic, local exposures, service availability and access, and system responses have major influence on people who use drugs. For policy makers to be effective, an understanding at the local level is needed. Methods: This retrospective epidemiologic study from 2019 through 2021 compares immediate and 20-months changes in overdose deaths from the pandemic start to 16 months before its arrival in Pinellas County, FL We examine toxicologic death records of 1,701 overdoses to identify relations with interdiction, and service delivery. Results: There was an immediate 49% increase (95% CI 23-82%, p < 0.0001) in overdose deaths in the first month following the first COVID deaths. Immediate increases were found for deaths involving alcohol (171%), heroin (108%), fentanyl (78%), amphetamines (55%), and cocaine (45%). Overdose deaths remained 27% higher (CI 4-55%, p = 0.015) than before the pandemic through 2021.Abrupt service reductions occurred when the pandemic began: in-clinic methadone treatment dropped by two-thirds, counseling by 38%, opioid seizures by 29%, and drug arrests by 56%. Emergency transport for overdose and naloxone distributions increased at the pandemic onset (12%, 93%, respectively) and remained higher through 2021 (15%, 377%,). Regression results indicate that lower drug seizures predicted higher overdoses, and increased 911 transports predicted higher overdoses. The proportion of excess overdose deaths to excess non-COVID deaths after the pandemic relative to the year before was 0.28 in Pinellas County, larger than 75% of other US counties. Conclusions: Service and interdiction interruptions likely contributed to overdose death increases during the pandemic. Relaxing restrictions on medical treatment for opioid addiction and public health interventions could have immediate and long-lasting effects when a major disruption, such as a pandemic, occurs. County level data dashboards comprised of overdose toxicology, and interdiction and service data, can help explain changes in overdose deaths. As a next step in predicting which policies and practices will best reduce local overdoses, we propose using simulation modeling with agent-based models to examine complex interacting systems.

Model-driven decision support: A community-based meta-implementation strategy to predict population impact.

PURPOSE: Standard tools for public health decision making such as data dashboards, trial repositories, and intervention briefs may be necessary but insufficient for guiding community leaders in optimizing local public health strategy. Predictive modeling decision support tools may be the missing link that allows community level decision makers to confidently direct funding and other resources to interventions and implementation strategies that will improve upon the status quo. METHODS: We describe a community-based model-driven decision support (MDDS) approach that requires community engagement, local data, and predictive modeling tools (agent-based modeling in our case studies) to improve decision-making on implementing strategies to address complex public health problems such as overdose deaths. We refer to our approach as a meta-implementation strategy as it provides guidance to a community on what intervention combinations and their required implementation strategies are needed to achieve desired outcomes. We use standard implementation measures including the Stages of Implementation Completion to assess adoption of this meta-implementation approach. RESULTS: Using two case studies, we illustrate how MDDS can be used to support decision making related to HIV prevention and reductions in overdose deaths at the city and county level. Even when community acceptance seems high, data acquisition and diffuse responsibility for implementing specific strategies recommended by modeling are barriers to adoption. CONCLUSIONS: MDDS has the capacity to improve community decision makers use of scientific knowledge by providing projections of the impact of intervention strategies under various scenarios. Further research is necessary to assess its effectiveness and the best strategies to implement it.

US payment policy for medications to treat opioid use disorder: landscape and opportunities.

Offering patients medications for opioid use disorder (MOUD) is the standard of care for opioid use disorder (OUD), but an estimated 75%-90% of people with OUD who could benefit from MOUD do not receive medication. Payment policy, defined as public and private payers' approaches to covering and reimbursing providers for MOUD, is 1 contributor to this treatment gap. We conducted a policy analysis and qualitative interviews (n = 21) and surveys (n = 31) with US MOUD payment policy experts to characterize MOUD insurance coverage across major categories of US insurers and identify opportunities for reform and innovation. Traditional Medicare, Medicare Advantage, and Medicaid all provide coverage for at least 1 formulation of buprenorphine, naltrexone, and methadone for OUD. Private insurance coverage varies by carrier and by plan, with methadone most likely to be excluded. The experts interviewed cautioned against rigid reimbursement models that force patients into one-size-fits-all care and endorsed future development and adoption of value-based MOUD payment models. More than 70% of experts surveyed reported that Medicare, Medicaid, and private insurers should increase payment for office- and opioid treatment program-based MOUD. Validation of MOUD performance metrics is needed to support future value-based initiatives.

Predicting whaler shark presence and interactions with humans in southern Queensland, Australia.

The Queensland Shark Control Program (QSCP) started in 1962 to reduce the number of shark-human incidents by deploying nets and drumlines across the most popular beaches. The program targets large shark species (white, tiger and bull sharks) that are potentially hazardous to bathers. However, this strategy is lethal for other sharks and marine wildlife, including threatened and endangered species. Thus, finding non-lethal strategies is a priority. To better manage shark-human interactions, establishing a better understanding of the factors that drive shark movement is key. Here we used sea surface temperature (SST), rainfall and distance to rivers as environmental variables to predict the presence of whaler sharks in southern Queensland based on 26 years of catch data from the QSCP. We found that SST is positively corelated to sharks caught by drumlines, while rainfall was associated with the number of sharks captured in shark nets. In addition, more sharks were captured by nets and drumlines further away from rivers, and nets captured roughly 10 times more sharks than drumlines over the period of study. In contrast to tiger sharks, the catch data indicate the number of whalers has not declined over the past 26 years. Our findings suggest that environmental variables can be used to predict the movement of large sharks and by incorporating this knowledge into management plans and public education programs, may ultimately reduce shark-human incidents.

An assessment of future rewilding potential in the United Kingdom.

Restoring ecosystems is an imperative for addressing biodiversity loss and climate change, and achieving the targets of the Kunming-Montreal Global Biodiversity Framework. One form of restoration, rewilding, may have particular promise but may also be precluded by requirements for other forms of land use now or in the future. This opportunity space is critical but challenging to assess. We explored the potential area available for rewilding in Great Britain until the year 2080 with a multisectoral land-use model with several distinct climatic and socioeconomic scenarios. By 2080, areas from 5000 to 7000 km2 were either unmanaged or managed in ways that could be consistent with rewilding across scenarios without conflicting with the provision of ecosystem services. Beyond these areas, another 24,000-42,000 km2 of extensive upland management could provide additional areas for rewilding if current patterns of implementation hold in the future. None of these areas, however, coincided reliably with ecosystems of priority for conservation: peatlands, ancient woodlands, or wetlands. Repeatedly, these ecosystems were found to be vulnerable to conversion. Our results are not based on an assumption of support for or benefits from rewilding and do not account for disadvantages, such as potential losses of cultural landscapes or traditional forms of management, that were beyond the modeled ecosystem services. Nevertheless, potential areas for rewilding emerge in a variety of ways, from intensification elsewhere having a substantial but inadvertent land-sparing effect, popular demand for environmental restoration, or a desire for exclusive recreation among the wealthy elite. Our findings therefore imply substantial opportunities for rewilding in the United Kingdom but also a need for interventions to shape the nature and extent of that rewilding to maintain priority conservation areas and societal objectives.

Una evaluación del potencial futuro de la resilvestración en el Reino Unido Resumen La restauración de ecosistemas es urgente para abordar la pérdida de biodiversidad y el cambio climático, así como para lograr los objetivos del Marco Mundial de Biodiversidad de Kunming­Montreal. Un método de restauración, la resilvestración, puede ser particularmente prometedor, aunque también puede ser excluido por los requerimientos para otras formas de uso de suelo actuales o en el futuro. Este espacio de oportunidad es crítico, pero también un reto para evaluar. Exploramos el área potencial disponible para el resilvestrado en Gran Bretaña hasta el año 2080 con un modelo multisectorial de uso de suelo con varios escenarios climáticos y socioeconómicos. Para este año, las áreas entre 5,000 y 7,000 km2 no estaban gestionadas o lo estaban, pero de manera que podían ser consistentes con el resilvestrado de los escenarios sin conflictuar el suministro de servicios ambientales. Más allá de estas áreas, otros 24,000­42,000 km2 de gestión extensiva tierra arriba podrían proporcionar áreas adicionales para el resilvestrado si los patrones actuales de implementación siguen en pie en el futuro. Sin embargo, ninguna de estas áreas coincidió de manera confiable con los ecosistemas de prioridad para la conservación: las turberas, bosques antiguos o humedales. Estos ecosistemas aparecieron varias veces como vulnerables a la conversión. Nuestros resultados no están basados en una suposición de apoyo para o los beneficios de la resilvestración y no consideran las desventajas, como la pérdida potencial de paisajes culturales o las maneras tradicionales de manejo, que estaban fuera del alcance de los servicios ambientales modelados. Sin embargo, las áreas potenciales para el resilvestrado emergen en una variedad de formas, desde la intensificación en otros lugares con un efecto de ahorro de tierras sustancial pero inadvertido, la demanda popular por la restauración ambiental o el deseo de una recreación exclusiva entre la elite acaudalada. Por lo tanto, nuestros descubrimientos implican una oportunidad sustancial para la resilvestración en el Reino Unido, aunque también una necesidad de intervenciones para moldear la naturaleza y la extensión de ese resilvestrado para mantener las áreas prioritarias de conservación y los objetivos sociales.

Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer.

BACKGROUND: Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product. METHODS: Starting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3'-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach. RESULTS: Calculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment. CONCLUSIONS: Overall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.

Biogeographic distribution of five Antarctic cyanobacteria using large-scale k-mer searching with sourmash branchwater.

Cyanobacteria form diverse communities and are important primary producers in Antarctic freshwater environments, but their geographic distribution patterns in Antarctica and globally are still unresolved. There are however few genomes of cultured cyanobacteria from Antarctica available and therefore metagenome-assembled genomes (MAGs) from Antarctic cyanobacteria microbial mats provide an opportunity to explore distribution of uncultured taxa. These MAGs also allow comparison with metagenomes of cyanobacteria enriched communities from a range of habitats, geographic locations, and climates. However, most MAGs do not contain 16S rRNA gene sequences, making a 16S rRNA gene-based biogeography comparison difficult. An alternative technique is to use large-scale k-mer searching to find genomes of interest in public metagenomes. This paper presents the results of k-mer based searches for 5 Antarctic cyanobacteria MAGs from Lake Fryxell and Lake Vanda, assigned the names Phormidium pseudopriestleyi FRX01, Microcoleus sp. MP8IB2.171, Leptolyngbya sp. BulkMat.35, Pseudanabaenaceae cyanobacterium MP8IB2.15, and Leptolyngbyaceae cyanobacterium MP9P1.79 in 498,942 unassembled metagenomes from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). The Microcoleus sp. MP8IB2.171 MAG was found in a wide variety of environments, the P. pseudopriestleyi MAG was found in environments with challenging conditions, the Leptolyngbyaceae cyanobacterium MP9P1.79 MAG was only found in Antarctica, and the Leptolyngbya sp. BulkMat.35 and Pseudanabaenaceae cyanobacterium MP8IB2.15 MAGs were found in Antarctic and other cold environments. The findings based on metagenome matches and global comparisons suggest that these Antarctic cyanobacteria have distinct distribution patterns ranging from locally restricted to global distribution across the cold biosphere and other climatic zones.

Acipenserid herpesvirus 2 genome and partial validation of a qPCR for its detection in white sturgeon Acipenser transmontanus.

White sturgeon Acipenser transmontanus is the primary species used for caviar and sturgeon meat production in the USA. An important pathogen of white sturgeon is acipenserid herpesvirus 2 (AciHV-2). In this study, 4 archived isolates from temporally discrete natural outbreaks spanning the past 30 yr were sequenced via Illumina and Oxford Nanopore Technologies platforms. Assemblies of approximately 134 kb were obtained for each isolate, and the putative ATPase subunit of the terminase gene was selected as a potential quantitative PCR (qPCR) target based on sequence conservation among AciHV-2 isolates and low sequence homology with other important viral pathogens. The qPCR was repeatable and reproducible, with a linear dynamic range covering 5 orders of magnitude, an efficiency of approximately 96%, an R2 of 0.9872, and an analytical sensitivity of 103 copies per reaction after 35 cycles. There was no cross-reaction with other known viruses or closely related sturgeon species, and no inhibition by sturgeon DNA. Clinical accuracy was assessed from white sturgeon juveniles exposed to AciHV-2 by immersion. Viral culture (gold standard) and qPCR were in complete agreement for both cell culture negative and cell culture positive samples, indicating that this assay has 100% relative accuracy compared to cell culture during an active outbreak. The availability of a whole-genome sequence for AciHV-2 and a highly specific and sensitive qPCR assay for detection of AciHV-2 in white sturgeon lays a foundation for further studies on host-pathogen interactions while providing a specific and rapid test for AciHV-2 in captive and wild populations.

Functional Hearing Preservation in Cochlear Implantation: The Miami Cocktail Effect.

OBJECTIVE: To investigate if pharmacological treatment with prednisone and L-N-acetylcysteine (STE + NAC) influence functional hearing preservation in cochlear implant (CI) surgery. STUDY DESIGNS: Preimplantation and postimplantation longitudinal case-control study. SETTING: Tertiary referral center. PATIENTS: Pediatric and adult recipients of CI with preimplantation functional hearing defined as an average of air-conducted thresholds at 125, 250, and 500 Hz (low-frequency pure-tone average [LFPTA]) <80 dB. INTERVENTIONS: Preimplantation and postimplantation audiometry. Weight-adjusted oral prednisone and L-N-acetylcysteine starting 2 days before surgery (Miami cocktail). Prednisone was continued for 3 days and L-N-acetylcysteine for 12 days after surgery, respectively. Cochlear implantation with conventional length electrodes. MAIN OUTCOME MEASURES: Proportion of patients with LFPTA <80 dB, and LFPTA change at 1-year postimplantation. RESULTS: All 61 patients received intratympanic and intravenous dexamethasone intraoperatively, with 41 patients receiving STE + NAC and 20 patients not receiving STE + NAC. At 1-year postimplantation, the proportion of functional hearing preservation was 83% in the STE + NAC group compared with 55% of subjects who did not receive STE + NAC ( p = 0.0302). The median LFPTA change for STE + NAC-treated and not treated subjects was 8.33 dB (mean, 13.82 ± 17.4 dB) and 18.34 dB (mean, 26.5 ± 23.4 dB), respectively ( p = 0.0401, Wilcoxon rank test). Perioperative STE + NAC treatment resulted in 10 dB of LFPTA better hearing than when not receiving this treatment. Better low-frequency preimplantation hearing thresholds were predictive of postimplantation functional hearing. No serious side effects were reported. CONCLUSION: Perioperative STE + NAC, "The Miami Cocktail," was safe and superior to intraoperative steroids alone in functional hearing preservation 1-year after cochlear implantation.

An artificial intelligence approach of feature engineering and ensemble methods depicts the rumen microbiome contribution to feed efficiency in dairy cows.

Genetic selection has remarkably helped U.S. dairy farms to decrease their carbon footprint by more than doubling milk production per cow over time. Despite the environmental and economic benefits of improved feed and milk production efficiency, there is a critical need to explore phenotypical variance for feed utilization to advance the long-term sustainability of dairy farms. Feed is a major expense in dairy operations, and their enteric fermentation is a major source of greenhouse gases in agriculture. The challenges to expanding the phenotypic database, especially for feed efficiency predictions, and the lack of understanding of its drivers limit its utilization. Herein, we leveraged an artificial intelligence approach with feature engineering and ensemble methods to explore the predictive power of the rumen microbiome for feed and milk production efficiency traits, as rumen microbes play a central role in physiological responses in dairy cows. The novel ensemble method allowed to further identify key microbes linked to the efficiency measures. We used a population of 454 genotyped Holstein cows in the U.S. and Canada with individually measured feed and milk production efficiency phenotypes. The study underscored that the rumen microbiome is a major driver of residual feed intake (RFI), the most robust feed efficiency measure evaluated in the study, accounting for 36% of its variation. Further analyses showed that several alpha-diversity metrics were lower in more feed-efficient cows. For RFI, [Ruminococcus] gauvreauii group was the only genus positively associated with an improved feed efficiency status while seven other taxa were associated with inefficiency. The study also highlights that the rumen microbiome is pivotal for the unexplained variance in milk fat and protein production efficiency. Estimation of the carbon footprint of these cows shows that selection for better RFI could reduce up to 5 kg of diet consumed per cow daily, potentially reducing up to 37.5% of CH4. These findings shed light that the integration of artificial intelligence approaches, microbiology, and ruminant nutrition can be a path to further advance our understanding of the rumen microbiome on nutrient requirements and lactation performance of dairy cows to support the long-term sustainability of the dairy community.

Pluripotency of a founding field: rebranding developmental biology.

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional funding apparatuses, frameworks for interdisciplinary innovative collaborations, pedagogical access, improved science communication, increased diversity and inclusion, and equity of resources to provide maximal impact to the community.

A cost-utility study of elective haemorrhoidectomies in Canada.

AIM: The aim was to estimate the 10-year cost-utility of haemorrhoidectomy surgery with preference-based measures of health using Canadian health utility measures and costs. METHODS: Patients undergoing elective haemorrhoidectomies by general and colorectal surgeons in British Columbia, Vancouver, between September 2015 and November 2022, completed preoperatively and postoperatively the EuroQol five-dimension five-level health-related quality of life questionnaire (EQ-5D-5L). Quality-adjusted life years (QALYs) attributable to surgery were calculated by discounting preoperative and postoperative health utility values derived from the EQ-5D-5L. Costs were measured from a health system perspective which incorporated costs of hospital stay and specialists' fees. Results are presented in 2021 Canadian dollars. RESULTS: Of 94 (47%) patients who completed both the preoperative and postoperative questionnaires, the mean gain in QALYs 10 years after surgery was 1.0609, assuming a 3.5% annual discounting rate. The average cost of the surgery was $3166. The average cost per QALY was $2985 when benefits of the surgery were assumed to accrue for 10 years. The cost per QALY was higher for women ($3821) compared with men ($2485). Participants over the age of 70 had the highest cost per QALY ($8079/QALY). CONCLUSIONS: Haemorrhoidectomies have been associated with significant gains in health status and are inexpensive relative to the associated gains in quality of life based on patients' perspectives of their improvement in health and well-being.

Forensic anthropologists and estimates of skeletal completeness: The impacts of training and experience.

Forensic anthropologists engage with numerous and diverse stakeholders in their casework. Regarding the recovery of human remains, these stakeholders may be interested in quantifying or qualifying the amount of remains recovered. How forensic anthropologists respond to such questions, whether verbally or in written reporting, has the potential to impact the trajectory of a case. However, communications about skeletal completeness are rarely discussed within the field. Current data-collection procedures recommend the use of inventories. This approach may be less feasible for complicated assemblages involving commingling or high degrees of fragmentation. Numerous methods exist to quantify the amount of skeletal remains present in complex or larger assemblages, but it remains unclear to what extent forensic anthropologists utilize these methods and whether factors like degree of expertise influence analysts' ability to report skeletal completeness consistently and precisely. A study was designed to examine differences between public and professional perceptions of skeletal completeness, presenting images of incomplete bones and skeletal remains. Survey participants were asked to assess the completeness of the remains in each image. Few patterns were observed regarding photographs of skeletal assemblages, but distinct differences were observed among individual bones between respondents with different degrees of expertise. These responses reflect potentially unexamined assumptions underlying assessments of incomplete bones and skeletal assemblages. This highlights the necessity of standardizing how we report estimates of completeness within the forensic anthropology community and how we discuss these results with external stakeholders. Completeness estimates must be either removed from reports and bench notes or annotated and cited clearly, as is standard with other aspects of forensic anthropological analysis. Several methods are summarized, with recommendations for integrating them into casework.

Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.

Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function AMBN variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of AMBN variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic AMBN variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read AMBN locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for AMBN-related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic AMBN variants have a more complex impact on human AI than previously reported.

Analysis of fibrinolytic shutdown in trauma patients with traumatic brain injury.

BACKGROUND: Coagulation profiles following major trauma vary depending on injury pattern and degree of shock. The physiologic mechanisms involved in coagulation function at any given time are varied and remain poorly understood. Thromboelastography (TEG) has been used evaluate coagulation profiles in the trauma population with some reports demonstrating a spectrum of fibrinolysis to fibrinolytic shutdown on initial presentation. The objective of this study was to evaluate the fibrinolytic profile of patients with TBI using thromboelastography (TEG). We hypothesized that patients with TBI would demonstrate low fibrinolytic activity. METHODS: All trauma activations at an ACS-verified level 1 trauma center received a TEG analysis upon arrival from December 2019 to June 2021. A retrospective review of the results and outcomes was conducted, and TBI patients were compared to patients without TBI. Linear regression was used to evaluate the effect of patient and injury factors on fibrinolysis. Hyperfibrinolysis was defined as LY30 â€‹> â€‹7.7%, physiologic fibrinolysis as LY30 0.6-7.7%, and fibrinolytic shutdown as LY30 â€‹< â€‹0.6%. RESULTS: A total of 1369 patients received an admission TEG analysis. Patients with TBI had a significantly higher median ISS (16 vs. 8, p â€‹< â€‹0.001), lower median admission Glasgow Coma Scale (14 vs. 15, p â€‹< â€‹0.001), longer intensive care unit length of stay (3 vs. 2 days, p â€‹< â€‹0.0001), increased ventilator days (216 vs. 183, p â€‹< â€‹0.001), higher mortality (14.6% vs. 5.1%, p â€‹< â€‹0.001), but lower shock index (0.6 vs. 0.7, p â€‹< â€‹0.0001) compared to those without TBI. Median LY30 was found to be decreased in the TBI group (0.1 vs. 0.2, p â€‹= â€‹0.0006). Patients with TBI were found to have a higher rate of fibrinolytic shutdown compared those without TBI (68.7% vs. 63.5%, p â€‹= â€‹0.054). ISS, sex, and shock index were found to be predictive of LY30 on linear regression, but TBI was not (Β: 0.09, SE: 0.277, p â€‹= â€‹0.745). The rate of DVT/PE did not appear to be elevated in patients with TBI (0.8%) and without TBI (1.2%). CONCLUSIONS: Trauma patients with and without TBI were found to have high rates of fibrinolytic shutdown. Although there was a high incidence of fibrinolytic shutdown, it did not appear to have an impact on the rate of thrombotic complications. The clinical significance of these results is unclear and differs significantly from recent reports which demonstrated that TBI is associated with a 25% rate of fibrinolytic shutdown. Further investigation is needed to better define the fibrinolytic pathway in patients with trauma and TBI to develop optimal treatment algorithms.

Missing a "Missing Self" Mechanism: Modeling and Detection of Ly49 Expression in Canine NK Cells.

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques. We interrogated the identified polymorphism/mutation in canine Ly49 and assessed the potential impact on structure using computational modeling of three-dimensional protein structure and protein-protein docking of canine Ly49 with MHC class I (MHC-I). Bulk and single-cell RNA-sequencing analysis was performed to detect gene expression of Ly49/KLRA1 in resting and activated NK cells. Tertiary protein structure demonstrated significant structural similarity to the known murine system. Molecular docking of canine Ly49 with MHC-I was favorable, converging at a single low-energy conformation. RNA sequencing revealed expression of Ly49/KLRA1 in both resting and activated NK cells and demonstrated almost exclusive expression of the gene in the NK cluster at the single-cell level. Despite prior reports of a mutated, nonfunctional canine Ly49, our data support that the protein product is predicted to bind to MHC-I in a comparable conformation to the murine system and is expressed in canine NK cells with upregulation following activation. Taken together, these data suggest that Ly49 is capable of recognizing MHC-I and therefore regulating NK cell function in dogs.

Engaging primary care clinicians in the selection of implementation strategies for toddler social-emotional health promotion in community health centers.

BACKGROUND: Social-emotional risk for subsequent behavioral health problems can be identified at toddler age, a period where prevention has a heightened impact. This study aimed to meaningfully engage pediatric clinicians, given the emphasis on health promotion and broad reach of primary care, to prepare an Implementation Research Logic Model to guide the implementation of a screening and referral process for toddlers with elevated social-emotional risk. METHOD: Using an adaptation of a previously published community partner engagement method, six pediatricians from community health centers (CHCs) comprised a Clinical Partner Work Group. The group was engaged in identifying determinants (barriers/facilitators), selecting and specifying strategies, strategy-determinant matching, a modified Delphi approach for strategy prioritization, and user-centered design methods. The data gathered from individual interviews, two group sessions, and a follow-up survey resulted in a completed Implementation Research Logic Model. RESULTS: The Clinical Partner Work Group identified 16 determinants, including barriers (e.g., patient access to electronic devices) and facilitators (e.g., clinician buy-in). They then selected and specified 14 strategies, which were prioritized based on ratings of feasibility, effectiveness, and priority. The highest-rated strategies (e.g., integration of the screener into the electronic health record) provided coverage of all identified barriers and comprised the primary implementation strategy "package" to be used and tested. CONCLUSIONS: Clinical partners provided important context and insights for implementation strategy selection and specification to support the implementation of social-emotional risk screening and referral in pediatric primary care. The methodology described herein can improve partner engagement in implementation efforts and increase the likelihood of success. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Retrospective Psychometrics and Effect Heterogeneity in Integrated Data Analysis: Commentary on the Special Issue.

The current special issue of Prevention Science indicates that momentum in using individual participant data (IPD) and integrative data analysis (IDA) to combine and synthesize findings in prevention science has accelerated over the past decade. In this commentary, we focus on two general themes involving methods for harmonizing measures and findings of effect heterogeneity. We describe methods for harmonization as retrospective psychometrics, requiring that we attend to the assumptions necessary for accurate measurement, but adjust our methods given the constraints of working with existing datasets that often involve different measures in different studies. We point to novel approaches for increasing confidence that semantic matching and empirical modeling used in these studies will yield accurate and valid measurements that can be combined in IDA. We also review findings about effect heterogeneity, emphasizing the importance of using etiologic and action theories to identify and evaluate sources of such effects. We note that all of the papers in this issue deserve careful attention, as they illustrate how prevention scientists are approaching the complexities of IDA and exploring novel methods for overcoming its challenges.