Towards a better future for DNA barcoding: Evaluating monophyly- and distance-based species identification using COI gene fragments of Dacini fruit flies.

The utility of a universal DNA 'barcode' fragment (658 base pairs of the Cytochrome C Oxidase I [COI] gene) has been established as a useful tool for species identification, and widely criticized as one for understanding the evolutionary history of a group. Large amounts of COI sequence data have been produced that hold promise for rapid species identification, for example, for biosecurity. The fruit fly tribe Dacini holds about a thousand species, of which 80 are pests of economic concern. We generated a COI reference library for 265 species of Dacini containing 5601 sequences that span most of the COI gene using circular consensus sequencing. We compared distance metrics versus monophyly assessments for species identification and although we found a 'soft' barcode gap around 2% pairwise distance, the exceptions to this rule dictate that a monophyly assessment is the only reliable method for species identification. We found that all fragments regularly used for Dacini fruit fly identification >450 base pairs long provide similar resolution. 11.3% of the species in our dataset were non-monophyletic in a COI tree, which is mostly due to species complexes. We conclude with recommendations for the future generation and use of COI libraries. We revise the generic assignment of Dacus transversus stat. rev. Hardy 1982, and Dacus perpusillus stat. rev. Drew 1971 and we establish Dacus maculipterus White 1998 syn. nov. as a junior synonym of Dacus satanas Liang et al. 1993.

The Florida Geriatric Head Trauma CT Clinical Decision Rule.

BACKGROUND: Several clinical decision rules have been devised to guide head computed tomography (CT) use in patients with minor head injuries, but none have been validated in patients 65 years or older. We aimed to derive and validate a head injury clinical decision rule for older adults. METHODS: We conducted a secondary analysis of an existing dataset of consecutive emergency department (ED) patients >65 years old with blunt head trauma. The main predictive outcomes were significant intracranial injury and Need for Neurosurgical Intervention on CT. The secondary outcomes also considered in the model development and validation were All Injuries and All Intracranial Injuries. Predictor variables were identified using multiple variable logistic regression, and clinical decision rule models were developed in a split-sample derivation cohort and then tested in an independent validation cohort. RESULTS: Of 5776 patients, 233 (4.0%) had significant intracranial injury and an additional 104 (1.8%) met CT criteria for Need for Neurosurgical Intervention. The best performing model, the Florida Geriatric Head Trauma CT Clinical Decision Rule, assigns points based on several clinical variables. If the points totaled 25 or more, a CT scan is indicated. The included predictors were arrival via Emergency Medical Services (+30 points), Glasgow Coma Scale (GCS) <15 (+20 points), GCS <14 (+50 points), antiplatelet medications (+17 points), loss of consciousness (+16 points), signs of basilar skull fracture (+50 points), and headache (+20 points). Utilizing this clinical decision rule in the validation cohort, a point total ≥25 had a sensitivity and specificity of 100.0% (95% CI: 96.0-100) and 12.3% (95% CI: 10.9-13.8), respectively, for significant intracranial injury and Need for Neurosurgical Intervention. CONCLUSIONS: The Florida Geriatric Head Trauma CT Clinical Decision Rule has the potential to reduce unnecessary CT scans in older adults, without compromising safe emergency medicine practice.

Sense of purpose in life and extending the cognitive healthspan: evidence from multistate survival modeling.

Having a sense of purpose in life predicts better maintenance of cognitive function in older adulthood and reduced risk of mild cognitive impairment (MCI) and dementia. However, little research has examined its influence on the rate of cognitive decline and length of cognitive healthspan. This study evaluated the role of sense of purpose on the risk and timing of transitions between normal cognition, MCI, and dementia. Older adults from the Memory and Aging Project (MAP; n = 1821) and the Health and Retirement Study (HRS; n = 10,542) were followed annually for 19 years and biennially for 12 years, respectively. Multistate survival models assessed whether sense of purpose predicted transitions across normal cognition, MCI, dementia, and death. More purposeful older adults had lower risk of developing MCI (HR = 0.82 in MAP; HR = 0.93 in HRS), higher likelihood of cognitive improvement, and longer cognitively healthy life expectancies. Results suggest sense of purpose may extend the cognitive healthspan.

Early childhood development strategy for the world's children with disabilities.

Early childhood is foundational for optimal and inclusive lifelong learning, health and well-being. Young children with disabilities face substantial risks of sub-optimal early childhood development (ECD), requiring targeted support to ensure equitable access to lifelong learning opportunities, especially in low- and middle-income countries. Although the Sustainable Development Goals, 2015-2030 (SDGs) emphasise inclusive education for children under 5 years with disabilities, there is no global strategy for achieving this goal since the launch of the SDGs. This paper explores a global ECD framework for children with disabilities based on a review of national ECD programmes from different world regions and relevant global ECD reports published since 2015. Available evidence suggests that any ECD strategy for young children with disabilities should consists of a twin-track approach, strong legislative support, guidelines for early intervention, family involvement, designated coordinating agencies, performance indicators, workforce recruitment and training, as well as explicit funding mechanisms and monitoring systems. This approach reinforces parental rights and liberty to choose appropriate support pathway for their children. We conclude that without a global disability-focussed ECD strategy that incorporates these key features under a dedicated global leadership, the SDGs vision and commitment for the world's children with disabilities are unlikely to be realised.

Anti-Müllerian hormone levels are associated with time to pregnancy in a prospective cohort study of 3,150 women.

OBJECTIVE: To study the association between AMH and time to pregnancy. While it has been hypothesized that serum anti-Müllerian hormone (AMH) levels may indicate the chance of conception, findings have been mixed. Given that any association is expected to be modest, and it is possible that previous studies have been underpowered, we investigated this relationship in the largest prospective cohort to date. DESIGN: Prospective time-to-pregnancy cohort study. SUBJECTS: 3,150 US women who had been trying to conceive for less than 3 months and had purchased a Modern Fertility Hormone Test. EXPOSURE: We developed a discrete time-to-event model utilizing a binomial complementary log-log error structure within a generalized additive modeling framework, adjusting for confounding factors such as age, BMI, parity, smoking status, PCOS, and others. Sensitivity analyses were performed in women with regular menstrual cycles (21-35 days), who did not report using fertility treatments, using alternate AMH categories (<0.7, 0.7-8.5, >8.5 ng/mL), and AMH as a continuous measure. MAIN OUTCOME MEASURES: Primary outcomes included cumulative conception probability within 12 cycles and relative fecundability per menstrual cycle. Conception was defined by a self-reported positive pregnancy test. RESULTS: Participants contributed 7.21 ± 5.32 cycles, with 1,325 (42.1%) achieving a pregnancy. Women with low AMH (<1ng/mL, n=427) had a lower chance of natural conception (Adjusted Hazard Ratio (adjHR 0.77, 95%CI 0.64, 0.94, p=0.009) compared to women with a normal AMH (1 - 5.5ng/mL). There was no difference between high (5.5+ ng/ml) and normal AMH categories (adjHR 1.11, 95% CI 0.94, 1.31, p=0.2). The inclusion of AMH improved the model (net reclassification index 0.10 [ 0.06 - 0.14); P<0.001). The instantaneous probability of conception was highest in cycle 4 across all AMH categories: the probability of natural conception was 11.2% (95% CI 9.0, 14.0) for low AMH, 14.3% (95% CI 12.3, 16.5) for normal AMH, and 15.7% (95%CI 12.9, 19.0) for high AMH. In the regular cycles sensitivity analysis (n=1,791), the low AMH group had a lower chance of conception (adjHR 0.77 95% CI 0.61, 0.97, p = 0.028) in the low AMH group compared to normal AMH, and similarly in the continuous model (adjHR 0.90; 95% CI 0.85-0.95, p<0.0001). CONCLUSION: Low AMH levels (<1 ng/ml) are independently associated with a modest but significant reduction in the chance of conception.

Frequency and Timing of Postoperative Complications After Outpatient Total Hip Arthroplasty.

Background: Although there have been several studies describing risk factors for complications after outpatient total hip arthroplasty (THA), data describing the timing of such complications is lacking. Methods: Patients who underwent outpatient or inpatient primary THA were identified in the 2012-2019 National Surgical Quality Improvement Program database. For 9 different 30-day complications, the median postoperative day of diagnosis was determined. Multivariable regressions were used to compare the risk of each complication between outpatient vs inpatient groups. Multivariable Cox proportional hazards modeling was used to evaluate the differences in the timing of each adverse event between the groups. Results: After outpatient THA, the median day of diagnosis for readmission was 12.5 (interquartile range 5-22), surgical site infection 15 (2-21), urinary tract infection 13.5 (6-19.5), deep vein thrombosis 13 (8-21), myocardial infarction 4.5 (1-7), pulmonary embolism 15 (8-25), sepsis 16 (9-26), stroke 2 (0-7), and pneumonia 6.5 (3-10). On multivariable regressions, outpatients had a lower relative risk (RR) of readmission (RR = 0.73), surgical site infection (RR = 0.72), and pneumonia (RR = 0.1), all P < .05. On multivariable cox proportional hazards modeling, there were no statistically significant differences in the timing of each complication between outpatient vs inpatient procedures (P > .05). Conclusions: The timing of complications after outpatient THA was similar to inpatient procedures. Consideration should be given to lowering thresholds for diagnostic testing after outpatient THA for each complication during the at-risk time periods identified here. Although extremely rare, this is especially important for catastrophic adverse events, which tend to occur early after discharge.

Whole Genomes Reveal Evolutionary Relationships and Mechanisms Underlying Gene-Tree Discordance in Neodiprion Sawflies.

Rapidly evolving taxa are excellent models for understanding the mechanisms that give rise to biodiversity. However, developing an accurate historical framework for comparative analysis of such lineages remains a challenge due to ubiquitous incomplete lineage sorting and introgression. Here, we use a whole-genome alignment, multiple locus-sampling strategies, and summary-tree and SNP-based species-tree methods to infer a species tree for eastern North American Neodiprion species, a clade of pine-feeding sawflies (Order: Hymenopteran; Family: Diprionidae). We recovered a well-supported species tree that-except for three uncertain relationships-was robust to different strategies for analyzing whole-genome data. Nevertheless, underlying gene-tree discordance was high. To understand this genealogical variation, we used multiple linear regression to model site concordance factors estimated in 50-kb windows as a function of several genomic predictor variables. We found that site concordance factors tended to be higher in regions of the genome with more parsimony-informative sites, fewer singletons, less missing data, lower GC content, more genes, lower recombination rates, and lower D-statistics (less introgression). Together, these results suggest that incomplete lineage sorting, introgression, and genotyping error all shape the genomic landscape of gene-tree discordance in Neodiprion. More generally, our findings demonstrate how combining phylogenomic analysis with knowledge of local genomic features can reveal mechanisms that produce topological heterogeneity across genomes.

Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: JACC Cardiovascular Imaging Position Statement.

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure operator proficiency are also discussed, thereby promoting the safety and efficacy of this innovative imaging modality to support expanding its future clinical applications.

Percutaneous Aspiration and Sclerotherapy as Primary Management for a Symptomatic Benign Adrenal Cyst.

Adrenal cysts are a rare benign adrenal pathology. Although the majority of adrenal cysts are asymptomatic, large cysts may present with debilitating symptoms of mass effect. Surgical adrenalectomy or cyst fenestration has been the primary mode of management for such symptomatic cysts, but these interventions can be associated with excessive morbidity, particularly when considered in the context of benign disease. Here, we present a case of a 34-year-old female with a longstanding, growing, benign left adrenal cyst associated with nonspecific abdominal symptoms. After multidisciplinary discussion, the patient was managed with primary ultrasound/fluoroscopic guided percutaneous sclerotherapy of her adrenal cyst. This technique achieved complete cyst resolution that was durable on 7-month follow-up and was associated with significant improvement of the patient's symptoms. This case illustrates the potential for primary percutaneous sclerotherapy for primary management of benign adrenal cysts.

Clinical outcomes for linked fixation of distal humerus fractures: a multi-center study.

BACKGROUND: O'Driscoll popularized the principle of linked column fixation for distal humerus fractures. Despite the linked column concept being widely accepted, there are few reported techniques to accomplish this goal. A novel device was designed based on the principles of linked columns. An interlocking beam is used to connect the medial and lateral plates, creating a unified fixed angle construct. Our primary objective was to report clinical outcomes across multiple institutions for a linking beam used in distal humerus fracture fixation. METHODS: A retrospective series was collected from five institutions for the TiBeam (Skeletal Dynamics, Miami, FL, USA) with a minimum follow-up of six months. Acute and chronic treatment of distal humerus fracture patterns, and all plate configurations were included for analysis. RESULTS: A total of 36 cases were collected at a mean age of 52 years and a mean follow-up of 19.3 months. AO C-type fractures were 56% of the series. The median MEPS was 85 (IQR 76.3 to 90), the median DASH was 21.4 (IQR 15.9 to 30), and the median VASa was 3.5 (IQR 2 to 5). An olecranon osteotomy was used in 86% of cases and an anatomic plate was used for fixation of the osteotomy in 94% of those cases. There were three cases of olecranon plate removal for a rate across the series of 13.7%. DISCUSSION: Our short-term results demonstrate satisfactory clinical outcomes with low rates of revision for distal humerus fracture fixed with a linking beam. Further, the rate of removal for the olecranon osteotomy plate was lower than historical reports for aggregate methods of osteotomy fixation.

PFHpA alters lipid metabolism and increases the risk of metabolic dysfunction-associated steatotic liver disease in youth-a translational research framework.

To address the growing epidemic of liver disease, particularly in pediatric populations, it is crucial to identify modifiable risk factors for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Per- and polyfluoroalkyl substances (PFAS) are persistent ubiquitous chemicals and have emerged as potential risk factors for liver damage. However, their impact on the etiology and severity of MASLD remains largely unexplored in humans. This study aims to bridge the gap between human and in vitro studies to understand how exposure to perfluoroheptanoic acid (PFHpA), one of the emerging PFAS replacements which accumulates in high concentrations in the liver, contributes to MASLD risk and progression. First, we showed that PFHpA plasma concentrations were significantly associated with increased risk of MASLD in obese adolescents. Further, we examined the impact of PFHpA on hepatic metabolism using 3D human liver spheroids and single-cell transcriptomics to identify major hepatic pathways affected by PFHpA. Next, we integrated the in vivo and in vitro multi-omics datasets with a novel statistical approach which identified signatures of proteins and metabolites associated with MASLD development triggered by PFHpA exposure. In addition to characterizing the contribution of PFHpA to MASLD progression, our study provides a novel strategy to identify individuals at high risk of PFHpA-induced MASLD and develop early intervention strategies. Notably, our analysis revealed that the proteomic signature exhibited a stronger correlation between both PFHpA exposure and MASLD risk compared to the metabolomic signature. While establishing a clear connection between PFHpA exposure and MASLD progression in humans, our study delved into the molecular mechanisms through which PFHpA disrupts liver metabolism. Our in vitro findings revealed that PFHpA primarily impacts lipid metabolism, leading to a notable increase of lipid accumulation in human hepatocytes after PFHpA exposure. Among the pathways involved in lipid metabolism in hepatocytes, regulation of lipid metabolism by PPAR-a showed a remarkable activation. Moreover, the translational research framework we developed by integrating human and in vitro data provided us biomarkers to identify individuals at a high risk of MASLD due to PFHpA exposure. Our framework can inform policies on PFAS-induced liver disease and identify potential targets for prevention and treatment strategies.

Mendelian randomization analyses clarify the effects of height on cardiovascular diseases.

An inverse correlation between stature and risk of coronary artery disease (CAD) has been observed in several epidemiologic studies, and recent Mendelian randomization (MR) experiments have suggested causal association. However, the extent to which the effect estimated by MR can be explained by cardiovascular, anthropometric, lung function, and lifestyle-related risk factors is unclear, with a recent report suggesting that lung function traits could fully explain the height-CAD effect. To clarify this relationship, we utilized a well-powered set of genetic instruments for human stature, comprising >1,800 genetic variants for height and CAD. In univariable analysis, we confirmed that a one standard deviation decrease in height (~6.5 cm) was associated with a 12.0% increase in the risk of CAD, consistent with previous reports. In multivariable analysis accounting for effects from up to 12 established risk factors, we observed a >3-fold attenuation in the causal effect of height on CAD susceptibility (3.7%, p = 0.02). However, multivariable analyses demonstrated independent effects of height on other cardiovascular traits beyond CAD, consistent with epidemiologic associations and univariable MR experiments. In contrast with published reports, we observed minimal effects of lung function traits on CAD risk in our analyses, indicating that these traits are unlikely to explain the residual association between height and CAD risk. In sum, these results suggest the impact of height on CAD risk beyond previously established cardiovascular risk factors is minimal and not explained by lung function measures.

Early Impressions and Adoption of the AtriAmp for Managing Arrhythmias Following Congenital Heart Surgery.

AtriAmp is a new medical device that displays a continuous real-time atrial electrogram on telemetry using temporary atrial pacing leads. Our objective was to evaluate early adoption of this device into patient care within our pediatric intensive care unit (PICU). This is a qualitative study using inductive analysis of semi-structured interviews to identify dominant themes. The study was conducted in a single-center, tertiary, academic 21-bed mixed PICU. The subjects were PICU multidisciplinary team members (Pediatric Cardiac Intensivists, PICU Nurse Practitioners, PICU nurses and Pediatric Cardiologists) who were early adopters of the AtriAmp (n = 14). Three prominent themes emerged: (1) Accelerated time from arrhythmia event to diagnosis and treatment; (2) Increased confidence in the accuracy of providers' arrhythmia diagnosis; and (3) Improvement in the ability to educate providers about post-operative arrhythmias. Providers also noted some learning curves, but none compromised medical care or clinical workflow. Insights from early adopters of AtriAmp signal the need for simplicity and fidelity in new PICU technologies. Our research suggests that such technologies can be pivotal to the support and growth of multi-disciplinary teams, even among those who do not participate in early implementation. Further research is needed to understand when and why novel technology adoption becomes widespread in high-stakes settings.

Initial management and outcomes of nonmalignant esophageal perforations: A Nationwide Inpatient Sample analysis.

BACKGROUND: Management of esophageal perforation includes open surgery, minimally invasive surgery, and endoscopic stent placement. This study analyzed initial treatment and the associated short-term outcomes. METHODS: A retrospective study using the National Inpatient Sample between October 2015 and December 2019 identified adults >18 years with esophageal perforation undergoing an initial nonelective esophageal procedure categorized into either open surgery, minimally invasive surgery, or endoscopic stent placement. Patients with esophageal cancer were excluded. Baseline characteristics and the van Walraven-weighted Elixhauser Comorbidity Index were identified. Outcomes included in-hospital mortality and postintervention complications. Univariable and multivariable Cox regression was used to compare in-hospital survival. RESULTS: In total, 3,345 patients met inclusion criteria: the median age was 62 years (interquartile range 50-72 years), and 1,310 (39%) were female. Open procedure was pursued in 2,650 (79%), minimally invasive surgery in 310 (9%), and endoscopic stent placement in 385 (12%) with no differences in van Walraven-weighted Elixhauser Comorbidity Index or mortality. Patients who underwent minimally invasive surgery had a greater proportion of gastrointestinal complications (P = .006); otherwise, there were no differences in postintervention complications. In total, 380 (11%) patients died and were significantly older, with greater van Walraven-weighted Elixhauser Comorbidity Index, and had more postintervention complications. Univariable Cox regression identified age (hazard ratio 1.95, P < .001), van Walraven-weighted Elixhauser Comorbidity Index (hazard ratio 1.06, P < .001), stent placement (hazard ratio 1.93, P = .045), and transfer from a health facility (HR 2.40, P = .049) as associated with decreased in-hospital survival. Multivariable Cox regression revealed age (hazard ratio 1.041, P < .001) and van Walraven-weighted Elixhauser comorbidity index (hazard ratio 1.055, P < .001) were associated with decreased in-hospital survival. CONCLUSION: Patients with esophageal perforation had an 11% in-hospital mortality rate and significant associated complications regardless of intervention. Increasing age and comorbidities are associated with poorer in-hospital survival.

Dynamic landscapes and protective immunity coordinated by influenza-specific lung-resident memory CD8+ T cells revealed by intravital imaging.

Lung-tissue-resident memory (TRM) CD8+ T cells are critical for heterosubtypic immunity against influenza virus (IAV) reinfection. How TRM cells surveil the lung, respond to infection, and interact with other cells remains unresolved. Here, we used IAV infection of mice in combination with intravital and static imaging to define the spatiotemporal dynamics of lung TRM cells before and after recall infection. CD69+CD103+ TRM cells preferentially localized to lung sites of prior IAV infection, where they exhibited patrolling behavior. After rechallenge, lung TRM cells formed tight clusters in an antigen-dependent manner. Transcriptomic analysis of IAV-specific TRM cells revealed the expression of several factors that regulate myeloid cell biology. In vivo rechallenge experiments demonstrated that protection elicited by TRM cells is orchestrated in part by interferon (IFN)-γ-mediated recruitment of inflammatory monocytes into the lungs. Overall, these data illustrate the dynamic landscapes of CD103+ lung TRM cells that mediate early protective immunity against IAV infection.

Childhood Lead Exposure Linked to Apple Cinnamon Fruit Puree Pouches - North Carolina, June 2023-January 2024.

Lead exposure is toxic even at low levels, resulting in impairments that can affect a child's lifelong success. In North Carolina, testing for lead is encouraged for all children at ages 1 and 2 years and required for children covered by Medicaid; investigations are performed to identify potential exposure sources for children with blood lead levels (BLLs) ≥5 µg/dL. During June-August 2023, routine lead testing identified four asymptomatic North Carolina children with BLLs ≥5 µg/dL. Home investigations identified only WanaBana brand apple cinnamon fruit puree pouches as a potential exposure source; product samples contained 1.9-3.0 ppm of lead. An expanded nationwide investigation led to identification of approximately 500 cases of childhood lead exposure believed to be linked to consumption of apple cinnamon purees, including 22 cases in North Carolina. Fewer than one half (45%) of the 22 North Carolina cases were among children covered by Medicaid. A coordinated multiagency communication strategy was implemented in North Carolina to notify consumers of the hazard and provide recommendations for preventing further exposure. The Food and Drug Administration issued a nationwide public health advisory on October 28, 2023; 2 days later, the manufacturer issued a voluntary recall. Routine testing of young children for lead exposure, combined with thorough environmental investigations, can identify emerging sources of lead exposure and limit further harm.

The Medicines Optimisation Innovation Centre: a dedicated centre driving innovation in medicines optimisation-impact and sustainability.

BACKGROUND: Sub-optimal medicines use is a challenge globally, contributing to poorer health outcomes, inefficiencies and waste. The Medicines Optimisation Innovation Centre (MOIC) was established in Northern Ireland by the Department of Health (DH) in 2015 to support implementation of the Medicines Optimisation Quality Framework. AIM: To demonstrate how MOIC informs policy and provides support to commissioners to improve population health and wellbeing. SETTING: MOIC is a regional centre with multidisciplinary and multi-sector clinical expertise across Health and Social Care and patient representation. DEVELOPMENT: Core funded by DH, MOIC has a robust governance structure and oversight programme board. An annual business plan is agreed with DH. Rigorous processes have been developed for project adoption and working collaboratively with industry. IMPLEMENTATION: MOIC has established partnerships with academia, industry, healthcare and representative organisations across Europe, participating in research and development projects and testing integrated technology solutions. A hosting programme has been established and evaluation and dissemination strategies have been developed. EVALUATION: MOIC has established numerous agreements, partnered in three large EU projects and strengthened networks globally with extensive publications and conference presentations. Informing pathway redesign, sustainability and COVID response, MOIC has also assisted in the development of clinical pharmacy services and antimicrobial stewardship in Europe and Africa. Northern Ireland has been recognised as a 4-star European Active and Healthy Ageing Reference Site and the Integrated Medicines Management model as an example of best practice in Central and Eastern Europe. CONCLUSION: MOIC has demonstrated considerable success and sustainability and is applicable to health systems globally.