Refracture Following Operative Treatment of Pediatric Both Bone Forearm Fractures.

INTRODUCTION: Both bone forearm fractures are common injuries in children. Most can be treated with reduction and casting. Those that fail nonoperative management can be treated with a plate or intramedullary fixation; however, refracture remains a problem. The goal of this study is to evaluate the refracture rate in both bone forearm fractures based on the mode of fixation. METHODS: Institutional board review approval was obtained. A retrospective chart review from 2010 to 2021 at a single tertiary care institution was conducted for all operative patients <18 years who sustained a both bone forearm fracture. Groups were stratified based on initial operative fixation type: both bones fixated using nails, 1 bone fixated with a nail; both bones plated, and 1 bone plated. Further review was conducted to identify refractures following initial operative treatment. Statistical analyses were conducted using the χ 2 test of independence and Fisher's exact test. RESULTS: In all, 402 operatively treated both bone forearm fracture patients were identified. Two hundred fifty-six of these patients underwent intramedullary fixation (average age 10.3y/o), while 146 patients received plate fixation (average age 13.8y/o). Fracture location was similar across the nailing and plating cohorts, most often occurring in the mid-shaft region. Patients aged ≤10 years refractured at a significantly higher rate than patients aged >10 years across all operative fixation cohorts (12.5% vs. 2.5%, P <0.001). Among the 256 patients who underwent intramedullary fixation, 61.3% had both bones treated (n=157/256), whereas 38.7% received single bone fixation (n=99/256). Of the 146 plate fixations, 84.4% had both bones fixed (n=123/146), and only 15.8% were treated with single bone fixation (n=23/146). In the intramedullary group, 15 patients sustained refractures, 11 of whom were treated with single bone fixation (11.1%, n=11/99) versus 4 with both both fixation (2.5%, n=4/157). Among the plating group, 7 patients sustained refractures, 6 with both bone fixation (4.9%, n=6/123) and 1 in single bone fixation (4.3%, n=1/23). Refractures were found to be significantly more prevalent among patients treated with single bone compared with both bone intramedullary nail fixation (11.1% vs. 2.5%, P =0.006). By fixated bone, single bone ulna fixations had a higher refracture rate compared with both bone fixations (12.1% vs. 3.6%, P =0.003). CONCLUSION: The overall refracture rate following operative treatment of both bone fractures is 5.5% and is similar between intramedullary and plate fixations. Overall, patients ≤10 years of age had a higher rate of refracture. Among single bone fixations, higher refracture was seen with intramedullary fixations, and when the radius was treated nonoperatively. Surgeons may be able to reduce the refracture rate by performing intramedullary fixation of both bones instead of only one bone. Effective postoperative counseling among younger patients may also decrease refracture rates.

Quality and Safety Practices Among Academic Obstetrics and Gynecology Departments.

The objective was to quantify resources devoted to quality and patient safety initiatives, to document the development and use of key performance indicator reports regarding patient outcomes and patient feedback, and to assess the culture of safety within academic obstetrics and gynecology departments. Chairs of academic obstetrics and gynecology departments were asked to complete a quality and safety assessment survey. Surveys were distributed to 138 departments, yielding 52 completed responses (37.7%). Five percent of departments reported including a patient representative on a quality committee. Most committee leaders (60.5%) and members (67.4%) received no compensation. Formal training was required in 28.8% of responding departments. Most departments monitored key performance metrics for inpatient outcomes (95.9%). Leaders scored their departments' culture of safety highly. Most departments provided no protected time to faculty devoted to quality efforts, generation of key performance indicators for inpatient activities was prevalent and integrating patient and community input remain unrealized opportunities.

Achilles Tendon Injuries in the Pediatric Population.

BACKGROUND: Achilles tendon injuries are common in adults, and there is extensive literature describing the injury characteristics and treatment of these adult injuries. However, Achilles injuries are rare in the pediatric population and as a result, there is limited research reported on this age group. We therefore sought to characterize the injury presentation, treatment and outcomes for pediatric patients with partial and complete Achilles injuries. METHODS: A retrospective chart review was conducted of patients aged 0-18 treated for Achilles tendon injuries at 2 geographically distinct tertiary institutions between 2008 and 2021. Data collected included demographics, injury characteristics, and treatment course. Injury types were separated into 2 cohorts: traumatic Achilles injuries and ruptures due to muscular contraction. Traumatic injuries were further delineated into 2 injury mechanisms: open injuries related to penetrating trauma and closed injuries related to blunt trauma. Standard descriptive analyses were utilized to summarize findings. RESULTS: Thirty-nine patients (43.6% female, median age 15 years) were identified, 29 (74.4%) of whom had complete tears. Twenty-five patients (64.1%) presented with traumatic injuries; among these, 48.0% (n=12/25) were ≤12 years. All patients ≤12 years sustained a traumatic injury. The most common traumatic mechanism was an open laceration due to penetrating trauma (68.0%), followed by closed ruptures associated with blunt trauma (32.0%). Fourteen patients (35.9%) presented with closed ruptures due to muscular contraction. Four patients (10.2%) had a prior history of clubfoot treated with Achilles tenotomy. Thirty-five patients (89.7%) were surgically treated with an open repair. The median immobilization period across all patients was 11 weeks (interquartile range: 10-12), starting most commonly with a posterior splint (46.2%) and concluding with a CAM boot (94.9%). Of patients with full follow-up data (n=22/39), all resumed normal activities, with a median clearance time of 6 months (interquartile range: 5-7.9). CONCLUSIONS: We found that older adolescents (≥14 y) were more likely to rupture their Achilles tendon through a forceful muscular contraction, whereas younger patients (≤12 y) were more likely to injure their Achilles via a traumatic mechanism. Most patients were treated operatively and returned to sports at a median time of 6 months. A further prospective study is warranted to better characterize treatment protocols and patient outcomes in this population. LEVEL OF EVIDENCE: Level-IV.

How Much Will My Child's ACL Reconstruction Cost? Availability and Variability of Price Estimates for Anterior Cruciate Ligament Reconstruction in the United States.

BACKGROUND: Despite recent policy efforts to increase price transparency, obtaining estimated prices for surgery remains difficult for most patients and families. PURPOSE: Assess availability and variability of cost and self-pay discounts for pediatric anterior cruciate ligament (ACL) reconstruction in the United States. METHODS: This was a prospective study using scripted telephone calls to obtain price estimates and self-pay discounts for pediatric ACL reconstruction. From July to August 2020, investigators called 102 hospitals, 51 "top-ranked" pediatric orthopaedic hospitals and 51 "non-top ranked" hospitals randomly selected, to impersonate the parent of an uninsured child with a torn ACL. Hospital, surgeon, and anesthesia price estimates, availability of a self-pay discount, and number of calls and days required to obtain price estimates were recorded for each hospital. Hospitals were compared on the basis of ranking, teaching status, and region. RESULTS: Only 31/102 (30.3%) hospitals provided a complete price estimate. Overall, 52.9% of top-ranked hospitals were unable to provide any price information versus 31.4% of non-top-ranked hospitals ( P =0.027). There was a 6.1-fold difference between the lowest and highest complete price estimates (mean estimate $29,590, SD $14,975). The mean complete price estimate for top-ranked hospitals was higher than for non-top-ranked hospitals ($34,901 vs. $25,207; P =0.07). The mean complete price estimate varied significantly across US region ( P =0.014), with the greatest mean complete price in the Northeast ($41,812). Altogether, 38.2% hospitals specified a self-pay discount, but only a fraction disclosed exact dollar or percentage discounts. The mean self-pay discount from top-ranked hospitals was larger than that of non-top-ranked hospitals ($18,305 vs. $9902; P =0.011). An average of 3.1 calls (range 1.0 to 12.0) over 5 days (range 1 to 23) were needed to obtain price estimates. CONCLUSION: Price estimates for pediatric sports medicine procedures can be challenging to obtain, even for the educated consumer. Top-ranked hospitals and hospitals in the Northeast region may charge more than their counterparts. In all areas, self-pay discounts can be substantial if they can be identified but they potentially create an information disadvantage for unaware patients needing to pay out-of-pocket. STUDY DESIGN: Economic; Level of Evidence II. WHAT IS KNOWN ABOUT THE SUBJECT: Previous studies have highlighted the importance of value-based health care decisions and deficits of price transparency in various fields including pediatric and orthopaedics procedures. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE: This study is the first to examine availability and variability of health care cost in pediatric sports medicine and the first to assess availability and magnitude of self-pay discounts, setting expectations for the uninsured patient incurring large out-of-pocket expenses.

Collection of Common Knee Patient-reported Outcome Instruments by Automated Mobile Phone Text Messaging in Pediatric Sports Medicine.

BACKGROUND: Patient-reported outcome (PRO) instruments measure health status in a variety of domains. With the proliferation of mobile phones, delivering PROs across patient-friendly platforms (eg, apps, text messaging) may increase completion rates, particularly among children. The purpose of this study was to validate the collection of common knee PROs in sports medicine with text messaging by correlating text-messaging responses with paper delivery in adolescents. METHODS: Patients presenting to a hospital-based pediatric orthopaedic sports medicine clinic with a knee injury were enrolled prospectively. Paper versions of the Pediatric International Knee Documentation Committee (Pedi-IKDC) Subjective Knee Evaluation Form and the Pediatric Functional Activity Brief Scale (Pedi-Fab Scale) were completed during initial clinic visits. Over the next 72 hours, patients completed the text message delivery of the Pedi-IKDC and Pedi-Fab Scale. Correlations between paper and text message delivery of the 2 PROs were assessed. RESULTS: Ninety-one patients (mean age: 16.0±2.0 y; 48% females) enrolled in the text-messaging study, with 55 (60.4%) completing the Pedi-Fab Scale, 48 (52.7%) completing the Pedi-IKDC, and 39 (42.9%) completing both PROs. The intraclass correlation coefficient between the paper and mobile phone delivery of the Pedi-Fab Scale was 0.95 (P<0.001; 95% confidence interval, 0.91-0.97). The intraclass correlation coefficient between the paper and mobile phone delivery of the Pedi-IKDC was 0.96 (P<0.001; 95% confidence interval, 0.93-0.98). Average Pedi-Fab scores on paper (M=12.7) and mobile phone (M=12.3) were not significantly different (P=0.52). Similarly, average Pedi-IKDC scores on paper (M=68.8) and mobile phone (M=67.7) were not significantly different (P=0.41). Average completion time for the text delivered Pedi-Fab and Pedi-IKDC were 102±224 and 159±155 minutes, respectively. High school enrollment (P=0.025), female sex (P=0.036), and race (P=0.002) were significantly associated with text completion of Pedi-IKDC. CONCLUSIONS: Text message delivery using mobile phones permits valid assessment of Pedi-IKDC and Pedi-Fab scores in adolescents. Questionnaire delivery by automated text messaging allows asynchronous response and may increase compliance and reduce the labor cost of collecting PROs. LEVEL OF EVIDENCE: Level III-prospective cohort study.

A Novel Low-Cost Surgical Simulation Tool for Pinning Supracondylar Humerus Fractures.

BACKGROUND: Simulation-based training is one way to improve basic competence for surgical trainees and thus improve patient safety. Closed reduction and percutaneous pinning of a supracondylar humerus fracture is a common procedure that encompasses many basic orthopaedic skills and has been identified as a residency milestone. Despite this, no quantitative tools exist to help learners attain this basic skill. This study seeks to validate a quantitative, low-cost simulation-based training tool for teaching orthopaedic surgery trainees the fundamentals of fracture stabilization with pins. METHODS: Two low-cost models were developed with simulated cancellous bone blocks and cortical bone sheets: a pinning agility tool to teach pin placement and redirection, and a low-cost construct stability tool to replicate pinning. A high-cost construct stability tool was cut using a pediatric supracondylar humerus model to simulate pinning a real fracture. Construct stability was assessed by adding weight until ∼1.6 mm of displacement was observed. Participants were tested naively on all 3 models and then completed a training session using only the low-cost models. Performance following training was then assessed and compared with fellowship-trained pediatric orthopaedic surgeons. Participants also rated their preintervention and postintervention confidence, skill, and knowledgeability. RESULTS: A total of 18 novice trainees participated (10 PGY1 and PGY2 orthopaedic surgery residents and 8 medical student members of the orthopaedic surgery interest club), whereas the reference group consisted of 7 orthopaedic surgery attendings. The subjects significantly improved their scores on both the low-cost (P=0.002) and high-cost (P<0.001) construct stability tools after the training with only the low-cost tools. Compared with the attending benchmark, trainee scores improved on the high-fidelity model from 31% preintervention to 86% postintervention and their pinning times decreased by 38%. Trainees reported increased knowledge, skill, and confidence after the intervention (P<0.001). CONCLUSIONS: A novel, low-cost simulation model and training session for supracondylar humerus fracture pinning resulted in improved performance in stabilizing a supracondylar humerus model and increased trainee knowledgeability, confidence, and skill. LEVEL OF EVIDENCE: Level II-economic.

Optimizing Phylogenomics with Rapidly Evolving Long Exons: Comparison with Anchored Hybrid Enrichment and Ultraconserved Elements.

Marker selection has emerged as an important component of phylogenomic study design due to rising concerns of the effects of gene tree estimation error, model misspecification, and data-type differences. Researchers must balance various trade-offs associated with locus length and evolutionary rate among other factors. The most commonly used reduced representation data sets for phylogenomics are ultraconserved elements (UCEs) and Anchored Hybrid Enrichment (AHE). Here, we introduce Rapidly Evolving Long Exon Capture (RELEC), a new set of loci that targets single exons that are both rapidly evolving (evolutionary rate faster than RAG1) and relatively long in length (>1,500 bp), while at the same time avoiding paralogy issues across amniotes. We compare the RELEC data set to UCEs and AHE in squamate reptiles by aligning and analyzing orthologous sequences from 17 squamate genomes, composed of 10 snakes and 7 lizards. The RELEC data set (179 loci) outperforms AHE and UCEs by maximizing per-locus genetic variation while maintaining presence and orthology across a range of evolutionary scales. RELEC markers show higher phylogenetic informativeness than UCE and AHE loci, and RELEC gene trees show greater similarity to the species tree than AHE or UCE gene trees. Furthermore, with fewer loci, RELEC remains computationally tractable for full Bayesian coalescent species tree analyses. We contrast RELEC to and discuss important aspects of comparable methods, and demonstrate how RELEC may be the most effective set of loci for resolving difficult nodes and rapid radiations. We provide several resources for capturing or extracting RELEC loci from other amniote groups.

A Multi-causal Model for Chronic Malnutrition and Anemia in a Population of Rural Coastal Children in Ecuador.

OBJECTIVES: Chronic malnutrition and anemia are prevalent in developing countries. This research aimed to determine the prevalence of chronic malnutrition and anemia and their associated factors in children under five using a multi-causal model in a rural community in the coast of Ecuador. METHODS: The study included 314 children under 5 years old who were residents of San Isidro, Ecuador. Indicators of chronic malnutrition and anemia were identified. Mothers/caregivers were surveyed on socio-economic and environmental conditions, feeding and care practices, access to health services and biological characteristics. Bivariate and multivariable Poisson regression were performed. RESULTS: The prevalence was 12.42% (n = 39) for chronic malnutrition and 16.98% (n = 54) for anemia. There was a significant and independent association between chronic malnutrition and family income less than $80 USD per month (Prevalence Ratio [PR] = 2.74, 95% CI 1.04, 7.20), maternal height less than 150 cm (PR 3.00, 95% CI 1.69, 5.32) and residence in a household with more than 4 children (PR 3.05, 95% CI 1.48, 6.29). Anemia was 2.57 times higher (95% CI 1.17, 5.65) in children with more than two episodes of diarrhea in the last 6 months. Prenatal care (5 to 8 visits) provided a protective effect for anemia (PR 0.48, 95% CI 0.27, 0.89). CONCLUSIONS FOR PRACTICE: Findings support the need for comprehensive interventions targeted toward chronic malnutrition and anemia in children from rural coastal communities. Improvement of socioeconomic conditions, family planning, prenatal care and reduction of diarrheal diseases should be prioritized.

Combined Danio rerio embryo morbidity, mortality and photomotor response assay: A tool for developmental risk assessment from chronic cyanoHAB exposure.

Freshwater harmful algal blooms produce a broad array of bioactive compounds, with variable polarity. Acute exposure to cyanotoxins can impact the liver, nervous system, gastrointestinal tract, skin, and immune function. Increasing evidence suggests chronic effects from low-level exposures of cyanotoxins and other associated bioactive metabolites of cyanobacterial origin. These sundry compounds persist in drinking and recreational waters and challenge resource managers in detection and removal. A systematic approach to assess the developmental toxicity of cyanobacterial metabolite standards was employed utilizing a robust and high throughput developmental Danio rerio embryo platform that incorporated a neurobehavioral endpoint, photomotor response. Subsequently, we applied the platform to cyanobacterial bloom surface water samples taken from temperate recreational beaches and tropical lake subsistence drinking water sources as a model approach. Dechorionated Danio rerio embryos were statically immersed beginning at four to six hours post fertilization at environmentally relevant concentrations, and then assessed at 24 h and 5 days for morbidity, morphological changes, and photomotor response. At least one assessed endpoint deviated significantly for exposed embryos for 22 out of 25 metabolites examined. Notably, the alkaloid lyngbyatoxin-a resulted in profound, dose-dependent morbidity and mortality beginning at 5 µg/L. In addition, hydrophobic components of extracts from beach monitoring resulted in potent morbidity and mortality despite only trace cyanotoxins detected. The hydrophilic extracts with several order of magnitude higher concentrations of microcystins resulted in no morbidity or mortality. Developmental photomotor response was consistently altered in environmental bloom samples, independent of the presence or concentration of toxins detected in extracts. While limited with respect to more polar compounds, this novel screening approach complements specific fingerprinting of acutely toxic metabolites with robust assessment of developmental toxicity, critical for chronic exposure scenarios.

Skin Transcriptomes of common bottlenose dolphins (Tursiops truncatus) from the northern Gulf of Mexico and southeastern U.S. Atlantic coasts.

Common bottlenose dolphins serve as sentinels for the health of their coastal environments as they are susceptible to health impacts from anthropogenic inputs through both direct exposure and food web magnification. Remote biopsy samples have been widely used to reveal contaminant burdens in free-ranging bottlenose dolphins, but do not address the health consequences of this exposure. To gain insight into whether remote biopsies can also identify health impacts associated with contaminant burdens, we employed RNA sequencing (RNA-seq) to interrogate the transcriptomes of remote skin biopsies from 116 bottlenose dolphins from the northern Gulf of Mexico and southeastern U.S. Atlantic coasts. Gene expression was analyzed using principal component analysis, differential expression testing, and gene co-expression networks, and the results correlated to season, location, and contaminant burden. Season had a significant impact, with over 60% of genes differentially expressed between spring/summer and winter months. Geographic location exhibited lesser effects on the transcriptome, with 23.5% of genes differentially expressed between the northern Gulf of Mexico and the southeastern U.S. Atlantic locations. Despite a large overlap between the seasonal and geographical gene sets, the pathways altered in the observed gene expression profiles were somewhat distinct. Co-regulated gene modules and differential expression analysis both identified epidermal development and cellular architecture pathways to be expressed at lower levels in animals from the northern Gulf of Mexico. Although contaminant burdens measured were not significantly different between regions, some correlation with contaminant loads in individuals was observed among co-expressed gene modules, but these did not include classical detoxification pathways. Instead, this study identified other, possibly downstream pathways, including those involved in cellular architecture, immune response, and oxidative stress, that may prove to be contaminant responsive markers in bottlenose dolphin skin.

Effect of sole or combined administration of nitrate and 3-nitro-1-propionic acid on fermentation and Salmonella survivability in alfalfa-fed rumen cultures in vitro.

Ruminal methanogenesis is a digestive inefficiency resulting in the loss of dietary energy consumed by the host and contributing to environmental methane emission. Nitrate is being investigated as a feed supplement to reduce rumen methane emissions but safety and efficacy concerns persist. To assess potential synergies of co-administering sub-toxic amounts of nitrate and 3-nitro-1-propionate (NPA) on fermentation and Salmonella survivability with an alfalfa-based diet, ruminal microbes were cultured with additions of 8 or 16mM nitrate, 4 or 12mM NPA or their combinations. All treatments decreased methanogenesis compared to untreated controls but volatile fatty acid production and fermentation of hexose were also decreased. Nitrate was converted to nitrite, which accumulated to levels inhibitory to digestion. Salmonella populations were enriched in nitrate only-treated cultures but not in cultures co- or solely treated with NPA. These results reveal a need for dose optimization to safely reduce methane production with forage-based diets.

Medial Epicondyle Fractures in the Pediatric Overhead Athlete.

The medial epicondyle serves as the proximal attachment of the medial ulnar collateral ligament and the origin of the flexor pronator musculature and as such it is responsible for resisting the main static and dynamic restraints to valgus force at the elbow. Fractures through the physis in the developing elbow are common and treatment remains controversial. Biomechanical modeling predicts that anterior should be the direction of greatest displacement. Anatomic considerations predict that anterior displacement should have the greatest effect on elbow stability and range of motion making the ulnar collateral ligament too loose in flexion and too tight in extension and potentially leading to valgus laxity in flexion and a block to full extension. In the elite overhead athlete, where elbow stability is critical both for sports performance and the long-term health of the elbow, assessment of anterior displacement is thus theoretically an important consideration. Standard radiographic views cannot adequately assess anterior displacement. Specialized radiographs and 3-dimensional modalities such as computerized tomography and magnetic resonance imaging can adequately assess anterior displacement and in the overhead athlete can sometimes aid in the decision-making process. Here, we present a review of the current literature and the rationale for a treatment algorithm for medial epicondyle fractures in the skeletally immature overhead athlete.

Prospective intraoperative syndesmotic evaluation during ankle fracture fixation: stress external rotation versus lateral fibular stress.

OBJECTIVES: We hypothesized that the method of stress external rotation more accurately reproduces the mechanism of injury, and therefore this diagnostic method more likely detects ankle instability than the fibular stress examination. DESIGN: Prospective cohort comparison study. SETTING: Level 1 trauma center. PATIENTS: Twenty-eight consecutive patients with unstable ankle fractures presenting within 7 days from the time of injury. Previous ankle surgical history or age younger than 18 years was excluded. INTERVENTION: Stress external rotation and lateral fibular stress examination was performed intraoperatively. MAIN OUTCOME MEASURE: Radiographic measurement of the tibiofibular clear space, tibiofibular overlap, and medial clear space were recorded. RESULTS: After normalization of the fluoroscopic measurements, there was no difference in detecting changes in tibiofibular clear space or tibiofibular overlap. However, there was a significant difference in detecting medial clear space widening with stress external rotation. Compared with lateral fibular stress, stress external rotation demonstrated a 35% increase (P < 0.05) in medial clear space widening. This difference correlates with the 1-2-mm difference of additional widening with stress external rotation. CONCLUSIONS: Untreated instability impacts patient outcomes. The difference in widening with stress external rotation was significantly greater than lateral fibular stress and appreciable on standard fluoroscopic views. Stress external rotation radiographs are a more reliable indicator of mortise instability than traditional lateral fibular stress. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Aspiration-related lung diseases.

Aspiration is a common but underrecognized clinicopathologic entity, with varied radiographic manifestations. Aspiration represents a spectrum of diseases, including diffuse aspiration bronchiolitis, aspiration pneumonitis, airway obstruction by foreign body, exogenous lipoid pneumonia, interstitial fibrosis, and aspiration pneumonia with or without lung abscess formation. Many patients who aspirate do not present with disease, suggesting that pathophysiology is related to a variety of factors, including decreased levels of consciousness, dysphagia, impaired mucociliary clearance, composition of aspirate, and impaired host defenses. In this pictorial essay, we will review the different types of aspiration lung diseases, focusing on their imaging features and differential diagnosis.

Sequence analysis of mutations and translocations across breast cancer subtypes.

Breast carcinoma is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone. This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis and responses to available therapy. Recurrent somatic alterations in breast cancer have been described, including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration. Previous DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements. Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA, TP53, AKT1, GATA3 and MAP3K1, we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking oestrogen and progesterone receptors and ERBB2 expression. The MAGI3-AKT3 fusion leads to constitutive activation of AKT kinase, which is abolished by treatment with an ATP-competitive AKT small-molecule inhibitor.

Panmixia postponed: ancestry-related assortative mating in contemporary human populations.

A study of two different populations reveals that in both the choice of a spouse is non-random not only in respect of broad ethnic group but also in regard to specific ancestries within that group. The cause of this surprising bias remains unclear.

Successive radiations, not stasis, in the South American primate fauna.

The earliest Neotropical primate fossils complete enough for taxonomic assessment, Dolichocebus, Tremacebus, and Chilecebus, date to approximately 20 Ma. These have been interpreted as either closely related to extant forms or as extinct stem lineages. The former hypothesis of morphological stasis requires most living platyrrhine genera to have diverged before 20 Ma. To test this hypothesis, we collected new complete mitochondrial genomes from Aotus lemurinus, Saimiri sciureus, Saguinus oedipus, Ateles belzebuth, and Callicebus donacophilus. We combined these with published sequences from Cebus albifrons and other primates to infer the mitochondrial phylogeny. We found support for a cebid/atelid clade to the exclusion of the pitheciids. Then, using Bayesian methods and well-supported fossil calibration constraints, we estimated that the platyrrhine most recent common ancestor (MRCA) dates to 19.5 Ma, with all major lineages diverging by 14.3 Ma. Next, we estimated catarrhine divergence dates on the basis of platyrrhine divergence scenarios and found that only a platyrrhine MRCA less than 21 Ma is concordant with the catarrhine fossil record. Finally, we calculated that 33% more change in the rate of evolution is required for platyrrhine divergences consistent with the morphologic stasis hypothesis than for a more recent radiation. We conclude that Dolichocebus, Tremacebus, and Chilecebus are likely too old to be crown platyrrhines, suggesting they were part of an extinct early radiation. We note that the crown platyrrhine radiation was concomitant with the radiation of 2 South American xenarthran lineages and follows a global temperature peak and tectonic activity in the Andes.

Partial island submergence and speciation in an adaptive radiation: a multilocus analysis of the Cuban green anoles.

Sympatric speciation is often proposed to account for species-rich adaptive radiations within lakes or islands, where barriers to gene flow or dispersal may be lacking. However, allopatric speciation may also occur in such situations, especially when ranges are fragmented by fluctuating water levels. We test the hypothesis that Miocene fragmentation of Cuba into three palaeo-archipelagos accompanied species-level divergence in the adaptive radiation of West Indian Anolis lizards. Analysis of morphology, mitochondrial DNA (mt DNA) and nuclear DNA in the Cuban green anoles (carolinensis subgroup) strongly supports three pre dictions made by this hypothesis. First, three geographical sets of populations, whose ranges correspond with palaeo-archipelago boundaries, are distinct and warrant recognition as independent evolutionary lineages or species. Coalescence of nuclear sequence fragments sampled from these species and the large divergences observed between their mtDNA haplotypes suggest separation prior to the subsequent unification of Cuba ca. 5 Myr ago. Second, molecular phylogenetic relationships among these species reflect historical geographical relationships rather than morphological similarity. Third, all three species remain distinct despite extensive geographical contact subsequent to island unification, occasional hybridization and introgression of mtDNA haplotypes. Allopatric speciation initiated during partial island submergence may play an important role in speciation during the adaptive radiation of Anolis lizards.

Niche lability in the evolution of a Caribbean lizard community.

Niche conservatism--the tendency for closely related species to be ecologically similar--is widespread. However, most studies compare closely related taxa that occur in allopatry; in sympatry, the stabilizing forces that promote niche conservatism, and thus inhibit niche shifts, may be countered by natural selection favouring ecological divergence to minimize the intensity of interspecific interactions. Consequently, the relative importance of niche conservatism versus niche divergence in determining community structure has received little attention. Here, we examine a tropical lizard community in which species have a long evolutionary history of ecological interaction. We find that evolutionary divergence overcomes niche conservatism: closely related species are no more ecologically similar than expected by random divergence and some distantly related species are ecologically similar, leading to a community in which the relationship between ecological similarity and phylogenetic relatedness is very weak. Despite this lack of niche conservatism, the ecological structuring of the community has a phylogenetic component: niche complementarity only occurs among distantly related species, which suggests that the strength of ecological interactions among species may be related to phylogeny, but it is not necessarily the most closely related species that interact most strongly.

Factor and latent class analysis of DSM-IVADHD symptoms in a school sample of Brazilian adolescents.

OBJECTIVE: To evaluate the validity of the multidimensional construct proposed by DSM-IV for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in a school sample of young Brazilian adolescents. METHOD: An instrument including all 18 DSM-IVADHD symptoms was administered to 1,013 students aged 12 to 14 years at 64 state schools by trained research assistants. Each symptom was rated on a Likert scale with five levels of severity (never, almost never, sometimes, frequently, and always). RESULTS: Using an exploratory factor analytic approach (principal components analysis), two factors were extracted. Factor I (hyperactivity-impulsivity) comprised eight DSM-IV hyperactive-impulsive symptoms with loadings > or =0.40. Factor II (inattention) included also eight DSM-IV symptoms of inattention. The two factors explained 34% of the total variance and had an interfactor correlation of 0.45. Latent class analysis demonstrated similar classes in males and females, but class structures were markedly different from previous analyses of parent report data. CONCLUSION: The findings support the appropriateness of the multidimensional construct introduced by DSM-IV in the diagnosis of ADHD in a different culture but emphasize the possible impact of different reporters on the results of structural model-testing.