Complexity of avian evolution revealed by family-level genomes.

Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method and the choice of genomic regions1-3. Here we address these issues by analysing the genomes of 363 bird species4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a marked degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous-Palaeogene boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that are a challenge to model due to either extreme DNA composition, variable substitution rates, incomplete lineage sorting or complex evolutionary events such as ancient hybridization. Assessment of the effects of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates and relative brain size following the Cretaceous-Palaeogene extinction event, supporting the hypothesis that emerging ecological opportunities catalysed the diversification of modern birds. The resulting phylogenetic estimate offers fresh insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies.

Placebo effect in randomized controlled trials for Meniere's disease: A meta-analysis.

PURPOSE: Meniere's Disease is a condition known for its recurrent vertigo, fluctuating sensorineural hearing loss, aural fullness, and tinnitus. Previous studies have demonstrated significant influence of placebo treatments. Our objective was to quantify the magnitude of the placebo effect in randomized controlled trials for Meniere's Disease. MATERIALS AND METHODS: A systematic review was performed by searching PubMed, SCOPUS, CINAHL, and Cochrane databases from inception through September 27, 2022. Data extraction, quality rating, and risk of bias assessment were performed by two independent reviewers. A meta-analysis of mean differences with 95 % confidence interval, weighted summary proportions, and proportion differences were calculated using random and fixed effects models. RESULTS: A total of 15 studies (N = 892) were included in the review. Significant improvement was seen in the functional level scores of the pooled placebo groups, with a mean difference of -0.6 points, (95%CI: -1.2 to -0.1). There was no difference in pure tone audiometry, speech discrimination score, or vertigo frequency at 1 and 3 months for the placebo group. Patient-reported vertigo episodes were improved in 52.5 % (95%CI: 39.2 to 65.5) of the placebo group and was significantly less than the pooled experimental group (90.1 %, 95%CI: 39.2 to 65.5, p < 0.001). CONCLUSIONS: The placebo effect in Meniere's Disease trials is associated with some symptomatic improvement in subjective outcomes, such as patient reported vertigo episodes. However, the clinical significance is questionable across other outcomes measures, especially when analyzing objective data. The extent and strength of the placebo effect continues to be a hurdle in the search for better treatment options.

The great divide: rhamnolipids mediate separation between P. aeruginosa and S. aureus.

The interactions between bacterial species during infection can have significant impacts on pathogenesis. Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic bacterial pathogens that can co-infect hosts and cause serious illness. The factors that dictate whether one species outcompetes the other or whether the two species coexist are not fully understood. We investigated the role of surfactants in the interactions between these two species on a surface that enables P. aeruginosa to swarm. We found that P. aeruginosa swarms are repelled by colonies of clinical S. aureus isolates, creating physical separation between the two strains. This effect was abolished in mutants of S. aureus that were defective in the production of phenol-soluble modulins (PSMs), which form amyloid fibrils around wild-type S. aureus colonies. We investigated the mechanism that establishes physical separation between the two species using Imaging of Reflected Illuminated Structures (IRIS), which is a non-invasive imaging method that tracks the flow of surfactants produced by P. aeruginosa. We found that PSMs produced by S. aureus deflected the surfactant flow, which in turn, altered the direction of P. aeruginosa swarms. These findings show that rhamnolipids mediate physical separation between P. aeruginosa and S. aureus, which could facilitate coexistence between these species. Additionally, we found that a number of molecules repelled P. aeruginosa swarms, consistent with a surfactant deflection mechanism. These include Bacillus subtilis surfactant, the fatty acids oleic acid and linoleic acid, and the synthetic lubricant polydimethylsiloxane. Lung surfactant repelled P. aeruginosa swarms and inhibited swarm expansion altogether at higher concentration. Our results suggest that surfactant interactions could have major impacts on bacteria-bacteria and bacteria-host relationships. In addition, our findings uncover a mechanism responsible for P. aeruginosa swarm development that does not rely solely on sensing but instead is based on the flow of surfactant.

Rescue of Alzheimer's disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells.

Alzheimer's disease (AD) is the most prevalent cause of dementia; microglia have been implicated in AD pathogenesis, but their role is still matter of debate. Our study showed that single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation rescued the AD phenotype in 5xFAD mice and that transplantation may prevent microglia activation. Indeed, complete prevention of memory loss and neurocognitive impairment and decrease of ß-amyloid plaques in the hippocampus and cortex were observed in the WT HSPC-transplanted 5xFAD mice compared with untreated 5xFAD mice and with mice transplanted with 5xFAD HSPCs. Neuroinflammation was also significantly reduced. Transcriptomic analysis revealed a significant decrease in gene expression related to "disease-associated microglia" in the cortex and "neurodegeneration-associated endothelial cells" in the hippocampus of the WT HSPC-transplanted 5xFAD mice compared with diseased controls. This work shows that HSPC transplant has the potential to prevent AD-associated complications and represents a promising therapeutic avenue for this disease.

An unusual case of Escherichia coli cellulitis and bacteremia in an immunocompetent patient.

Cellulitis secondary to Escherichia coli (E. coli) is a rare phenomenon, particularly in an immunocompetent patient. We report an unusual case of an immunocompetent 84-year-old female presenting with E.coli bacteremia and E. coli cellulitis in the right lower leg. We postulate that bacterial translocation from the gastrointestinal tract to the bloodstream is the most likely source of E. coli infection. Whilst a common condition, cellulitis can pose a diagnostic and therapeutic challenge when a causative organism is not identified. Thorough investigation and consideration of atypical organisms such as E.coli are essential to permit targeted antimicrobial therapy and prevent patient deterioration.

Machine Learning-Based Aggression Detection in Children with ADHD Using Sensor-Based Physical Activity Monitoring.

Aggression in children is highly prevalent and can have devastating consequences, yet there is currently no objective method to track its frequency in daily life. This study aims to investigate the use of wearable-sensor-derived physical activity data and machine learning to objectively identify physical-aggressive incidents in children. Participants (n = 39) aged 7 to 16 years, with and without ADHD, wore a waist-worn activity monitor (ActiGraph, GT3X+) for up to one week, three times over 12 months, while demographic, anthropometric, and clinical data were collected. Machine learning techniques, specifically random forest, were used to analyze patterns that identify physical-aggressive incident with 1-min time resolution. A total of 119 aggression episodes, lasting 7.3 ± 13.1 min for a total of 872 1-min epochs including 132 physical aggression epochs, were collected. The model achieved high precision (80.2%), accuracy (82.0%), recall (85.0%), F1 score (82.4%), and area under the curve (89.3%) to distinguish physical aggression epochs. The sensor-derived feature of vector magnitude (faster triaxial acceleration) was the second contributing feature in the model, and significantly distinguished aggression and non-aggression epochs. If validated in larger samples, this model could provide a practical and efficient solution for remotely detecting and managing aggressive incidents in children.

"It Goes Hand in Hand with Us Trying to Get More Kids to Play" Stakeholder Experiences in a Sport and Active Recreation Voucher Program.

Vouchers that reduce the cost of sport and active recreation participation have been shown to increase children's and adolescent's physical activity levels. Yet, the influence of government-led voucher programs on the capacity of sport and active recreation organisations is unclear. This qualitative study explored the experiences of stakeholders in the sport and recreation sector that were engaged in implementing the New South Wales (NSW) Government's Active Kids voucher program in Australia. Semi-structured interviews were conducted with 29 sport and active recreation providers. Interview transcriptions were analysed by a multidisciplinary team using the Framework method. Overall, participants reported that the Active Kids voucher program was an acceptable intervention to address the cost barrier to participation for children and adolescents. Three main steps influenced the capacity of organisations to deliver their sport and recreation programs and the voucher program: (1) Implementation priming-alignment of the intervention aims with stakeholder priorities and early information sharing, (2) Administrative ease-enhanced technology use and establishment of simple procedures, and (3) Innovation impacts-enablement of staff and volunteers to address barriers to participation for their participants. Future voucher programs should include strategies to enhance the capacity of sport and active recreation organisations to meet program guidelines and increase innovation.

Intravenous immunoglobulin treatment for refractory pyoderma gangrenosum.

BACKGROUND: Intravenous immunoglobulins (IVIG) have been increasingly used for various inflammatory dermatoses with success. Small case series and case reports suggest a role for IVIG in the management of refractory pyoderma gangrenosum (PG). OBJECTIVE: The objective was to study the characteristics of PG patients treated with IVIG and the efficacy and safety of IVIG for patients with refractory PG. METHODS: An analysis was performed of all patients with PG treated with IVIG from 2012 to 2022 at an Australian tertiary hospital seeing a high volume of PG patients. RESULTS: We identified 12 patients, 9 females and 3 males, with median age of 61 years (29-77) at IVIG commencement. All patients were taking systemic corticosteroid therapy prior to IVIG treatment, and all had been treated with a steroid-sparing agent-including ten patients who had been treated with a biologic agent. IVIG was used with corticosteroids in one patient, concurrently with a steroid-sparing agent in nine patients and with a biologic agent in eight patients. Eleven patients demonstrated treatment response to IVIG-six with excellent response and five with good response. Three patients had complete healing of their most active ulcer. One patient did not respond to IVIG. Nine patients were able to wean their prednisolone dose and one patient was able to cease prednisolone. Four adverse events were recorded, and only one patient had to cease treatment due to aseptic meningitis and headaches. CONCLUSION: Our experience suggests that IVIG may be an efficacious treatment for patients with refractory PG due to its pleiotropic and immunomodulatory effects, particularly for patients with malignancy or other systemic conditions where high-dose immunosuppressive agents are contraindicated.

Comparative anatomy of the passerine carpometacarpus helps illuminate the early fossil record of crown Passeriformes.

The hyper-diverse clade Passeriformes (crown group passerines) comprises over half of extant bird diversity, yet disproportionately few studies have targeted passerine comparative anatomy on a broad phylogenetic scale. This general lack of research attention hinders efforts to interpret the passerine fossil record and obscures patterns of morphological evolution across one of the most diverse clades of extant vertebrates. Numerous potentially important crown passeriform fossils have proven challenging to place phylogenetically, due in part to a paucity of phylogenetically informative characters from across the passerine skeleton. Here, we present a detailed analysis of the morphology of extant passerine carpometacarpi, which are relatively abundant components of the passerine fossil record. We sampled >70% of extant family-level passerine clades (132 extant species) as well as several fossils from the Oligocene of Europe and scored them for 54 phylogenetically informative carpometacarpus characters optimised on a recently published phylogenomic scaffold. We document a considerable amount of previously undescribed morphological variation among passerine carpometacarpi, and, despite high levels of homoplasy, our results support the presence of representatives of both crown Passeri and crown Tyranni in Europe during the Oligocene.

VEXAS syndrome: A dermatological perspective.

VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic mutation) syndrome is a genetically defined disorder identified in 2020, describing patients with inflammatory syndromes associated with haematological dysfunction. It is a severe, treatment-resistant condition, with estimated mortality between 40% and 63%. A wide range of cutaneous manifestations have been described. Here, we report on two patients with treatment-resistant neutrophilic dermatosis and myelodysplastic syndrome, who were subsequently diagnosed with VEXAS syndrome. Our cases highlight the need for dermatologists' awareness of this novel condition and to initiate early referral to haematologists for appropriate multidisciplinary care.

Longitudinal Trends in Case Histories and Rehabilitative Device Assessments at Low Vision Examinations.

SIGNIFICANCE: Understanding longitudinal changes in why individuals frequent low-vision clinics is crucial for ensuring that patient care keeps current with changing technology and changing lifestyles. Among other findings, our results suggest that reading remains a prevailing patient complaint, with shifting priorities toward technology-related topics. PURPOSE: This study aimed to understand changes in patient priorities and patient care in low vision over the past decade. METHODS: We conducted a retrospective study of examination records (2009 to 2019, 3470 examinations) from two U.S. low-vision clinics. Automated word searches summarized two properties of the records: topics discussed during the case history and types of rehabilitative devices assessed. Logistic regression was used to model the effects of examination year, patient age, patient sex, and level of visual impairment. RESULTS: Collapsing across all years, the most common topic discussed was reading (78%), followed by light-related topics (71%) and technology (59%). Whereas the odds of discussing reading trended downward over the decade (odds ratio, 0.57; P = .03), technology, social interaction, mobility, and driving trended upward (odds ratios, 4.53, 3.31, 2.71, and 1.95; all P 's < 0.001). The most frequently assessed devices were tinted lenses (95%). Over time, video magnifier and spectacle assessments trended downward (odds ratios, 0.64 and 0.72; P = .004, 0.04), whereas assessments of other optical aids increased. The data indicate several consistent differences among patient demographics. CONCLUSIONS: Reading is likely to remain a prevailing patient complaint, but an increase in technology-related topics suggests shifting priorities, particularly in younger demographics. "Low-tech" optical aids have remained prominent in low-vision care even as "high-tech" assistive devices in the marketplace continue to advance.

Communication Gaps Between Providers and Caregivers of Patients in a Pediatric Emergency Department.

Communication gaps between the healthcare team and caregivers of pediatric patients can result in negative consequences. This study aims to identify specific words and phrases used in a pediatric emergency department (ED) that are unclear or confusing to caregivers. Research assistants at the Primary Children's Hospital recorded caregivers' responses to the question, "What words or phrases have been used during this visit that are unclear or don't make sense to you?" Across all steps in the care process, 62 of 220 participants (28.2%) reported unclear words and phrases used by the healthcare team. Responses recorded after the discharge step had the highest proportion of communication problems, followed by the initial evaluation and then the update step (χ2 [2, N = 220] = 6.30, P = .043). Themes among responses included ED logistics, signs/symptoms, the diagnostic process, treatment/procedures, general confusion, and language barriers. These results provide feedback to pediatric emergency medicine providers about potential communication gaps and point to a need for further efforts to train providers in the practice of high-quality communication.

A Lagerstätte from Australia provides insight into the nature of Miocene mesic ecosystems.

Reduced precipitation in the Miocene triggered the geographic contraction of rainforest ecosystems around the world. In Australia, this change was particularly pronounced; mesic rainforest ecosystems that once dominated the landscape transformed into the shrublands, grasslands, and deserts of today. A lack of well-preserved fossils has made it difficult to understand the nature of Australian ecosystems before the aridification. Here, we report on an exceptionally well-preserved rainforest biota from New South Wales, Australia. This Konservat-Lagerstätte hosts a rich diversity of microfossils, plants, insects, spiders, and vertebrate remains preserved in goethite. We document evidence for several species interactions including predation, parasitism, and pollination. The fossils are indicative of an oxbow lake in a mesic rainforest and suggest that rainforest distributions have shifted since the Miocene. The variety of fossils preserved, together with high fidelity of preservation, allows for unprecedented insights into the mesic ecosystems that dominated Australia during the Miocene.

Exploring Relationships Between Grit, Belonging, Institutional Compassion, Pandemic Stress, and Goal Progress Among Emerging Adult Post-Secondary Students.

Grit and belonging are consistently important factors in emerging adult academic outcomes (Morrow & Ackermann, 2012). This study examines the role of grit (i.e., goal perseverance, consistency of interest, and adaptability), belonging (i.e., sense of fitting in and feeling valued), and perceived institutional compassion (i.e., care/support and resources for students in pandemic-related responses) in emerging adults' academic goal pursuits amid COVID-19 challenges. Emerging adult participants (age 18-24; N = 258) representing a diverse sample of traditional, full-time, undergraduate students across the United States (60% women; 47.31% White, 18.46% Black/African American, 17.31% Asian, 10.77% Hispanic/Latino/a/x), completed an online survey assessing pandemic-related stress, grit, belonging, goal pursuits, and the newly developed Institutional Compassion Scale (Schmahl, 2021). Unexpectedly, pandemic-related stress was unrelated to student assessments of their progress toward academic short- and long-term goals. But grit and belonging were associated with pandemic-related stress: high stress is associated with a weaker sense of belonging and with lower grit. Institutional compassion was associated with all three major study variables: grit, sense of belonging, and stress. Higher institutional compassion was associated with a greater sense of belonging and less pandemic-related stress. The importance of grit, belonging, and particularly institutional compassion are discussed as they pertain to emerging adults' perceptions of themselves as progressing toward their goals during stressful periods such as the onset of the COVID-19 pandemic.

Hypoglycemia in Older People With Type 2 Diabetes: Prevention and Treatment Strategies for Outpatient and Long-Term Care Facility Settings.

Hypoglycemia in the older population is a significant problem accounting for increased hospitalizations, emergency room visits, health care costs, and decreased quality of life. Older patients are more susceptible to hypoglycemia because of the increased prevalence of comorbidities requiring multiple medications, age-related physiologic changes, and a progressive decline in health. Older patients are less likely to present with symptoms of hypoglycemia and symptoms may frequently appear at a lower threshold of blood glucose than in younger patients. Consequently, preventing and treating hyperglycemia in older patients can be challenging. If mismanaged, the impact of hypoglycemia in these patients can lead to acute and chronic negative outcomes. Insulin and sulfonylureas should be closely monitored, and deprescribing should be routinely considered in older patients at high risk for hypoglycemia.

Prognostic Significance of Preoperative Neutrophil-Lymphocyte Ratio in Vascular Surgery: Systematic Review and Meta-Analysis.

OBJECTIVE: The global burden of surgical vascular disease is increasing and with it, the need for cost-effective, accessible prognostic biomarkers to aid optimization of peri-operative outcomes. The neutrophil-lymphocyte ratio (NLR) is emerging as a potential candidate biomarker for perioperative risk stratification. We therefore performed this systematic review and meta-analysis on the prognostic value of elevated preoperative NLR in vascular surgery. METHODS: We searched Embase (Ovid), Medline (Ovid), and the Cochrane Library database from inception to June 2019. Screening was performed, and included all peer-reviewed original research studies reporting preoperative NLR in adult emergent and elective vascular surgical patients. Studies were assessed for bias and quality of evidence using a standardized tool. Meta-analysis was performed by general linear (mixed-effects) modelling where possible, and otherwise a narrative review was conducted. Between-study heterogeneity was estimated using the Chi-squared statistic and explored qualitatively. RESULTS: Fourteen studies involving 5,652 patients were included. The overall methodological quality was good. Elevated preoperative NLR was associated with increased risk of long-term mortality (HR 1.40 [95%CI: 1.13-1.74], Chi-squared 60.3%, 7 studies, 3,637 people) and short-term mortality (OR: 3.08; 95%CI: 1.91-4.95), Chi-squared 66.59%, 4 studies, 945 people). Outcome measures used by fewer studies such as graft patency and amputation free survival were assessed via narrative review. CONCLUSIONS: NLR is a promising, readily obtainable, prognostic biomarker for mortality outcomes following vascular surgery. Heterogeneity in patient factors, severity of vascular disease, and type of vascular surgery performed renders direct comparison of outcomes from the current literature challenging. This systematic review supports further investigation for NLR measurement in pre-vascular surgical risk stratification. In particular, the establishment of a universally accepted NLR cut-off value is of importance in real-world implementation of this biomarker.