Neonatal hemophagocytic lymphohistiocytosis: A meta-analysis of 205 cases.

BACKGROUND: Neonatal hemophagocytic lymphohistiocytosis (nHLH), defined as HLH that presents in the first month of life, is clinically devastating. There have been few large descriptive studies of nHLH. OBJECTIVES: The objective of this study was to perform a meta-analysis of published cases of nHLH. METHODS: A comprehensive literature database search was performed. Cases of HLH were eligible for inclusion if clinical analysis was performed at age ≤30 days. Up to 70 variables were extracted from each case. RESULTS: A total of 544 studies were assessed for eligibility, and 205 cases of nHLH from 142 articles were included. The median age of symptom onset was day of life 3 (interquartile range [IQR]: 0-11, n = 141). Median age at diagnosis was day of life 15 (IQR: 6-27, n = 87). Causes of HLH included familial HLH (48%, n = 99/205), infection (26%, n = 53/205), unknown (17%, n = 35/205), macrophage activation syndrome/rheumatologic (2.9%, n = 4/205), primary immune deficiency (2.0%, n = 5/205), inborn errors of metabolism (2.4%, n = 5/205), and malignancy (2.0%, n = 4/205). Fever was absent in 19% (n = 28/147) of all neonates and 39% (n = 15/38) of preterm neonates. Bicytopenia was absent in 26% (n = 47/183) of patients. Central nervous system (CNS) manifestations were reported in 63% of cases (n = 64/102). Liver injury (68%, n = 91/134) and/or liver failure (24%, n = 32/134) were common. Flow cytometry was performed in 22% (n = 45/205) of cases. Many patients (63%, n = 121/193) died within the period of reporting. Discernable values for HLH diagnostic criteria were reported between 30% and 83% of the time. CONCLUSIONS: Evaluation of nHLH requires rapid testing for a wide range of differential diagnoses. HLH diagnostic criteria such as fever and bicytopenia may not occur as frequently in the neonatal population as in older pediatric populations. Neurologic and hepatic manifestations frequently occur in the neonatal population. Current reports of nHLH suggest a high mortality rate. Future publications containing data on nHLH should improve reporting quality by reporting all clinically relevant data.

Nasopharyngeal Swabs in Pediatric Patients With Thrombocytopenia and Anticoagulant Use.

BACKGROUND: Nasopharyngeal (NP) swabbing is a technique that is commonly used to test pediatric patients for viral infections with increased use during the coronavirus disease 2019 pandemic. Complications from NP swabbing are rare and seem to occur more frequently in patients at risk of bleeding. Little is known about institutional or individual practices and experiences with NP swab testing in pediatric patients with risk factors for bleeding. METHODS: We conducted a survey study of pediatric hematology/oncology (PHO) attending physicians to assess practices and experiences with NP swab testing in pediatric patients with thrombocytopenia and/or on anticoagulation. RESULTS: There were 130 total respondents (5.6%, n = 130/2327) from 6 countries. Relatively few respondents (n = 17/130, 13.1%) reported that their institution had a policy specifying a lower-level platelet cutoff for patients undergoing NP swabbing. The median platelet cutoff below which NP swabs are not performed according to existing policies is 30,000×10(9)/L (interquartile range: 20,000 to 40,000). The median cutoff based on the opinion of the respondents was 10,000 (interquartile range: 10,000 to 20,000). There were 24 episodes of epistaxis among PHO patients that were NP swabbed; many adverse events (56.5%, n = 13/23) were described as persistent, severe, and/or required intervention. Three reported cases of epistaxis with anticoagulation or antiplatelet therapy occurred in patients with concomitant thrombocytopenia. Only 1 respondent (n = 1/130, 0.7%) reported an institutional policy for limiting NP swabs in patients on anticoagulant therapy. NP (66.9%) and nares (33.1%) were the most common sources of coronavirus disease 2019 testing that were reported. CONCLUSION: A small percentage of institutions in this survey have a policy restricting NP swabs in PHO patients. The discrepancy between lower platelet cutoffs proposed by experts and institutional policy suggests that existing policies may be too conservative. Expert guidelines are needed on this topic. Other bleeding risk factors (eg, aspirin use and von Willebrand disease) should be considered in policies and guidelines.

Impacts of fludioxonil resistance on global gene expression in the necrotrophic fungal plant pathogen Sclerotinia sclerotiorum.

BACKGROUND: The fungicide fludioxonil over-stimulates the fungal response to osmotic stress, leading to over-accumulation of glycerol and hyphal swelling and bursting. Fludioxonil-resistant fungal strains that are null-mutants for osmotic stress response genes are easily generated through continual sub-culturing on sub-lethal fungicide doses. Using this approach combined with RNA sequencing, we aimed to characterise the effects of mutations in osmotic stress response genes on the transcriptional profile of the important agricultural pathogen Sclerotinia sclerotiorum under standard laboratory conditions. Our objective was to understand the impact of disruption of the osmotic stress response on the global transcriptional regulatory network in an important agricultural pathogen. RESULTS: We generated two fludioxonil-resistant S. sclerotiorum strains, which exhibited growth defects and hypersensitivity to osmotic stressors. Both had missense mutations in the homologue of the Neurospora crassa osmosensing two component histidine kinase gene OS1, and one had a disruptive in-frame deletion in a non-associated gene. RNA sequencing showed that both strains together differentially expressed 269 genes relative to the parent during growth in liquid broth. Of these, 185 (69%) were differentially expressed in both strains in the same direction, indicating similar effects of the different point mutations in OS1 on the transcriptome. Among these genes were numerous transmembrane transporters and secondary metabolite biosynthetic genes. CONCLUSIONS: Our study is an initial investigation into the kinds of processes regulated through the osmotic stress pathway in S. sclerotiorum. It highlights a possible link between secondary metabolism and osmotic stress signalling, which could be followed up in future studies.

Is sleep position associated with glenohumeral shoulder pain and rotator cuff tendinopathy: a cross-sectional study.

BACKGROUND: Glenohumeral pain and rotator cuff tendinopathy (RCT) are common musculoskeletal complaints with high prevalence among working populations. The primary proposed pathophysiologic mechanisms are sub-acromial RC tendon impingement and reduced tendon blood flow. Some sleep postures may increase subacromial pressure, potentially contributing to these postulated mechanisms. This study uses a large population of workers to investigate whether there is an association between preferred sleeping position and prevalence of: (1) shoulder pain, and (2) rotator cuff tendinopathy. METHODS: A cross-sectional analysis was performed on baseline data from a multicenter prospective cohort study. Participants were 761 workers who were evaluated by questionnaire using a body diagram to determine the presence of glenohumeral pain within 30 days prior to enrollment. The questionnaire also assessed primary and secondary preferred sleep position(s) using 6 labeled diagrams. All workers underwent a structured physical examination to determine whether RCT was present. For this study, the case definition of RCT was glenohumeral pain plus at least one of a positive supraspinatus test, painful arc and/or Neer's test. Prevalence of glenohumeral pain and RCT were individually calculated for the primary and secondary sleep postures and odds ratios were calculated. RESULTS: Age, sex, Framingham cardiovascular risk score and BMI had significant associations with glenohumeral pain. For rotator cuff tendinopathy, increasing age, Framingham risk score and Hand Activity Level (HAL) showed significant associations. The sleep position anticipated to have the highest risk of glenohumeral pain and RCT was paradoxically associated with a decreased prevalence of glenohumeral pain and also trended toward being protective for RCT. Multivariable logistic regression showed no further significant associations. CONCLUSION: This cross-sectional study unexpectedly found a reduced association between one sleep posture and glenohumeral pain. This cross-sectional study may be potentially confounded, by participants who are prone to glenohumeral pain and RCT may have learned to avoid sleeping in the predisposing position. Longitudinal studies are needed to further evaluate a possible association between glenohumeral pain or RCT and sleep posture as a potential risk factor.

Physical activity level and body composition in a multiethnic sample of school children in Hawaii.

BACKGROUND: Obesity, particularly in Native Hawaiians, is an important health risk. A possible contributing factor to obesity is reduced physical activity levels. AIM: This study investigates the relationship between measured levels of physical activity and body composition in two grade cohorts of school children of Native Hawaiian/Pacific Islander (NHPI) and non-NHPI ethnicity. METHODS: A sample of 105 Kindergarteners and third graders were measured for adiposity, physical fitness, and physical activity levels. Ethnicity was determined from genealogical surveys. BMI, waist circumference (WC) and body fat percentage derived from air displacement plethysmography were used to evaluate adiposity. Maximal oxygen consumption (VO2max/kg) was estimated and total energy expenditure (TEE), physical activity level (PAL) and percentage of time inactive (PTI) were determined using the Flex-heart rate method. RESULTS: VO2max, but not TEE, PAL or PTI, was significantly correlated with BMI in Kindergarteners; while VO2max and PAL were negatively correlated with BMI, PAL was significantly negatively correlated with WC and PTI was positively correlated with fat percentage among third graders. There were no significant ethnic differences in VO2max, TEE, PAL or PTI. CONCLUSIONS: PAL and PTI are moderately related to adiposity measures, and there are no ethnic differences in physical activity or fitness measures in this sample.

Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): a cluster-randomised controlled trial.

BACKGROUND: The increasing prevalence of type 2 diabetes poses a major public health challenge. Population-based screening and early treatment for type 2 diabetes could reduce this growing burden. However, uncertainty persists around the benefits of screening for type 2 diabetes. We assessed the effect of a population-based stepwise screening programme on mortality. METHODS: In a pragmatic parallel group, cluster-randomised trial, 33 general practices in eastern England were randomly assigned by the method of minimisation in an unbalanced design to: screening followed by intensive multifactorial treatment for people diagnosed with diabetes (n=15); screening plus routine care of diabetes according to national guidelines (n=13); and a no-screening control group (n=5). The study population consisted of 20,184 individuals aged 40-69 years (mean 58 years), at high risk of prevalent undiagnosed diabetes, on the basis of a previously validated risk score. In screening practices, individuals were invited to a stepwise programme including random capillary blood glucose and glycated haemoglobin (HbA(1c)) tests, a fasting capillary blood glucose test, and a confirmatory oral glucose tolerance test. The primary outcome was all-cause mortality. All participants were flagged for mortality surveillance by the England and Wales Office of National Statistics. Analysis was by intention-to-screen and compared all-cause mortality rates between screening and control groups. This study is registered, number ISRCTN86769081. FINDINGS: Of 16,047 high-risk individuals in screening practices, 15,089 (94%) were invited for screening during 2001-06, 11,737 (73%) attended, and 466 (3%) were diagnosed with diabetes. 4137 control individuals were followed up. During 184,057 person-years of follow up (median duration 9·6 years [IQR 8·9-9·9]), there were 1532 deaths in the screening practices and 377 in control practices (mortality hazard ratio [HR] 1·06, 95% CI 0·90-1·25). We noted no significant reduction in cardiovascular (HR 1·02, 95% CI 0·75-1·38), cancer (1·08, 0·90-1·30), or diabetes-related mortality (1·26, 0·75-2·10) associated with invitation to screening. INTERPRETATION: In this large UK sample, screening for type 2 diabetes in patients at increased risk was not associated with a reduction in all-cause, cardiovascular, or diabetes-related mortality within 10 years. The benefits of screening might be smaller than expected and restricted to individuals with detectable disease. FUNDING: Wellcome Trust; UK Medical Research Council; National Health Service research and development support; UK National Institute for Health Research; University of Aarhus, Denmark; Bio-Rad.

First measurement of the form factors in the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e).

The beauty to up quark coupling constant |V(ub)| can be extracted from B → ρ e+ ν(e) combined with the form factors for D → K* e+ ν(e) and B → V ℓ+ ℓ- and D → ρ e+ ν(e). Using the entire CLEO-c ψ(3770) → DD event sample, corresponding to an integrated luminosity of 818 pb(-1) and approximately 5.4×10(6) DD events, we measure the form factors for the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e) for the first time and the branching fractions with improved precision. A four-dimensional unbinned maximum likelihood fit determines the form factor ratios to be V(0)/A1(0)=1.48±0.15±0.05 and A2(0)/A1(0)=0.83±0.11±0.04. Assuming Cabibbo-Kobayashi-Maskawa unitarity, the known D meson lifetimes, and our measured branching fractions we obtain the form factor normalizations A1(0), A2(0), and V(0). We also present a measurement of the branching fraction for D+ → ω e+ ν(e) with improved precision.

Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation.

In a wide variety of animal species, oocyte maturation is arrested temporarily at prophase of meiosis I (ref. 1). Resumption of meiosis requires activation of cyclin-dependent kinase-1 (CDK1, p34cdc2), one component of maturation-promoting factor (MPF). The dual specificity phosphatases Cdc25a, Cdc25b and Cdc25c are activators of cyclin-dependent kinases; consequently, they are postulated to regulate cell-cycle progression in meiosis and mitosis as well as the DNA-damage response. We generated Cdc25b-deficient (Cdc25b-/-) mice and found that they are viable. As compared with wildtype cells, fibroblasts from Cdc25b-/- mice grew vigorously in culture and arrested normally in response to DNA damage. Female Cdc25b-/- mice were sterile, and Cdc25b-/- oocytes remained arrested at prophase with low MPF activity. Microinjection of wildtype Cdc25b mRNA into Cdc25b-/- oocytes caused activation of MPF and resumption of meiosis. Thus, Cdc25b-/- female mice are sterile because of permanent meiotic arrest resulting from the inability to activate MPF. Cdc25b is therefore essential for meiotic resumption in female mice. Mice lacking Cdc25b provide the first genetic model for studying the mechanisms regulating prophase arrest in vertebrates.

An Exploratory Study of Bone Health Among Native Hawaiian Women in Rural Hawai'i.

INTRODUCTION: The purpose of this study was to obtain baseline data on bone mass density for Native Hawaiian women and to better understand the socio-cultural context for assessing bone health and risk of osteoporosis for this underserved population. METHOD: A sequential mixed-method design guided by Leininger's Culture Care Theory of Diversity and Universality consisted of two phases: (a) an initial exploratory focus group and (b) dual-energy X-ray absorptiometry (DEXA) scans and individual interviews. Data were analyzed using descriptive statistics and thematic analysis. RESULTS: Phase a (n = 12) suggested that Native Hawaiian women have limited knowledge of bone health, but recognize traditional and cultural ways of health. Phase b (n = 50) showed that Native Hawaiian women have healthy bones, according to the T-score results. The interviews suggested that perspectives of bone health are culturally anchored. DISCUSSION: Understanding cultural values and practices are vital for care. Preliminary recommendations for health professionals are included.

ZEB1 loss increases glioma stem cell tumorigenicity and resistance to chemoradiation.

OBJECTIVE: Glioblastoma has been known to be resistant to chemotherapy and radiation, whereas the underlying mechanisms of resistance have not been fully elucidated. The authors studied the role of the transcription factor ZEB1 (zinc finger E-box-binding homeobox 1 protein), which is associated with epithelial-mesenchymal transition (EMT) and is central to the stemness of glioblastoma, to determine its role in therapeutic resistance to radiation and chemotherapy. The authors previously demonstrated that ZEB1 is deleted in a majority of glioblastomas. METHODS: The authors explored resistance to therapy in the context of ZEB1 loss and overexpression in glioma stem cells (GSCs) and in patient data. RESULTS: Patients with ZEB1 loss had a shorter survival time than patients with wild-type ZEB1 in both the high- and low-MGMT groups. Consistent with the clinical data, mice implanted with ZEB1 knockdown GSCs showed shortened survival compared with mice inoculated with nonsilencing control (NS) short-hairpin RNA (shRNA) GSC glioblastoma. ZEB1-deleted GSCs demonstrated increased tumorigenicity with regard to proliferation and invasion. Importantly, GSCs that lose ZEB1 expression develop enhanced resistance to chemotherapy, radiotherapy, and combined chemoradiation. ZEB1 loss may lead to increased HER3 expression through the HER3/Akt pathway associated with this chemoresistance. Conversely, overexpression of ZEB1 in GSCs that are ZEB1 null leads to increased sensitivity to chemoradiation. CONCLUSIONS: The study results indicate that ZEB1 loss in cancer stem cells confers resistance to chemoradiation and uncovers a potentially targetable cell surface receptor in these resistant cells.

TP53-PTEN-NF1 depletion in human brain organoids produces a glioma phenotype in vitro.

Glioblastoma (GBM) is fatal and the study of therapeutic resistance, disease progression, and drug discovery in GBM or glioma stem cells is often hindered by limited resources. This limitation slows down progress in both drug discovery and patient survival. Here we present a genetically engineered human cerebral organoid model with a cancer-like phenotype that could provide a basis for GBM-like models. Specifically, we engineered a doxycycline-inducible vector encoding shRNAs enabling depletion of the TP53, PTEN, and NF1 tumor suppressors in human cerebral organoids. Designated as inducible short hairpin-TP53-PTEN-NF1 (ish-TPN), doxycycline treatment resulted in human cancer-like cerebral organoids that effaced the entire organoid cytoarchitecture, while uninduced ish-TPN cerebral organoids recapitulated the normal cytoarchitecture of the brain. Transcriptomic analysis revealed a proneural GBM subtype. This proof-of-concept study offers a valuable resource for directly investigating the emergence and progression of gliomas within the context of specific genetic alterations in normal cerebral organoids.

Histopathological effects of the Yen-Tc toxin complex from Yersinia entomophaga MH96 (Enterobacteriaceae) on the Costelytra zealandica (Coleoptera: Scarabaeidae) larval midgut.

Yersinia entomophaga MH96, which was originally isolated from the New Zealand grass grub, Costelytra zealandica, produces an orally active proteinaceous toxin complex (Yen-Tc), and this toxin is responsible for mortality in a range of insect species, mainly within the Coleoptera and Lepidoptera. The genes encoding Yen-Tc are members of the toxin complex (Tc) family, with orthologs identified in several other bacterial species. As the mechanism of Yen-Tc activity remains unknown, a histopathological examination of C. zealandica larvae was undertaken in conjunction with cultured cells to identify the effects of Yen-Tc and to distinguish the contributions that its individual subunit components make upon intoxication. A progressive series of events that led to the deterioration of the midgut epithelium was observed. Additionally, experiments using a cell culture assay system were carried out to determine the cellular effects of intoxication on cells after topical application and the transient expression of Yen-Tc and its individual components. While observations were broadly consistent with those previously reported for other Tc family members, some differences were noted. In particular, the distinct stepwise disintegration of the midgut shared features associated with both apoptosis and necrotic programmed cell death pathways. Second, we observed, for the first time, a contribution of toxicity from two chitinases associated with the Yen-Tc complex. Our findings were suggestive of the activities encoded within the subunit components of Yen-Tc targeting different sites along putative programmed cell death pathways. Given the observed broad host range for Yen-Tc, these targeted loci are likely to be widely shared among insects.

Impacts of e-health on the outcomes of care in low- and middle-income countries: where do we go from here?

E-health encompasses a diverse set of informatics tools that have been designed to improve public health and health care. Little information is available on the impacts of e-health programmes, particularly in low- and middle-income countries. We therefore conducted a scoping review of the published and non-published literature to identify data on the effects of e-health on health outcomes and costs. The emphasis was on the identification of unanswered questions for future research, particularly on topics relevant to low- and middle-income countries. Although e-health tools supporting clinical practice have growing penetration globally, there is more evidence of benefits for tools that support clinical decisions and laboratory information systems than for those that support picture archiving and communication systems. Community information systems for disease surveillance have been implemented successfully in several low- and middle-income countries. Although information on outcomes is generally lacking, a large project in Brazil has documented notable impacts on health-system efficiency. Meta-analyses and rigorous trials have documented the benefits of text messaging for improving outcomes such as patients' self-care. Automated telephone monitoring and self-care support calls have been shown to improve some outcomes of chronic disease management, such as glycaemia and blood pressure control, in low- and middle-income countries. Although large programmes for e-health implementation and research are being conducted in many low- and middle-income countries, more information on the impacts of e-health on outcomes and costs in these settings is still needed.

Fungicide resistance characterized across seven modes of action in Botrytis cinerea isolated from Australian vineyards.

BACKGROUND: Botrytis bunch rot, caused by Botrytis cinerea, is an economically important disease of grapes in Australia and across grape-growing regions worldwide. Control of this disease relies on canopy management and the application of fungicides. Fungicide application can lead to the selection of resistant B. cinerea populations, which has an adverse effect on the management of the disease. Characterizing the distribution and severity of resistant B. cinerea populations is needed to inform resistance management strategies. RESULTS: In this study, 724 isolates were sampled from 76 Australian vineyards during 2013-2016 and were screened against seven fungicides with different modes of action (MOAs). The resistance frequencies for azoxystrobin, boscalid, fenhexamid, fludioxonil, iprodione, pyrimethanil and tebuconazole were 5%, 2.8%, 2.1%, 6.2%, 11.6%, 7.7% and 2.9%, respectively. Nearly half of the resistant isolates (43.8%) were resistant to more than one of the fungicides tested. The frequency of vineyards with at least one isolate simultaneously resistant to one, two, three, four or five fungicides was 19.7%, 7.9%, 6.6%, 10.5% and 2.6%. Resistance was associated with previously published genotypes in CytB (G143A), SdhB (H272R/Y), Erg27 (F412S), Mrr1 (D354Y), Bos1 (I365S, N373S + Q369P, I365S + D757N) and Pos5 (V273I, P319A, L412F/V). Novel genotypes were also described in Mrr1 (S611N, D616G), Pos5 (V273L) and Cyp51 (P347S). Expression analysis was used to characterize fludioxonil-resistant isolates exhibiting overexpression (6.3-9.6-fold) of the ABC transporter gene AtrB (MDR1 phenotype). CONCLUSION: Resistance frequencies were lower when compared to most previously published surveys of B. cinerea resistance in grape and other crops. Nevertheless, continued monitoring of critical MOAs used in Australian vineyards is recommended. © 2021 Society of Chemical Industry.

The main virulence determinant of Yersinia entomophaga MH96 is a broad-host-range toxin complex active against insects.

Through transposon mutagenesis and DNA sequence analysis, the main disease determinant of the entomopathogenic bacterium Yersinia entomophaga MH96 was localized to an ~32-kb pathogenicity island (PAI) designated PAI(Ye96). Residing within PAI(Ye96) are seven open reading frames that encode an insecticidal toxin complex (TC), comprising not only the readily recognized toxin complex A (TCA), TCB, and TCC components but also two chitinase proteins that form a composite TC molecule. The central TC gene-associated region (~19 kb) of PAI(Ye96) was deleted from the Y. entomophaga MH96 genome, and a subsequent bioassay of the ΔTC derivative toward Costelytra zealandica larvae showed it to be innocuous. Virulence of the ΔTC mutant strain could be restored by the introduction of a clone containing the entire PAI(Ye96) TC gene region. As much as 0.5 mg of the TC is released per 100 ml of Luria-Bertani broth at 25°C, while at 30 or 37°C, no TC could be detected in the culture supernatant. Filter-sterilized culture supernatants derived from Y. entomophaga MH96, but not from the ΔTC strain grown at temperatures of 25°C or less, were able to cause mortality. The 50% lethal doses (LD50s) of the TC toward diamondback moth Plutella xylostella and C. zealandica larvae were defined as 30 ng and 50 ng, respectively, at 5 days after ingestion. Histological analysis of the effect of the TC toward P. xylostella larva showed that within 48 h after ingestion of the TC, there was a general dissolution of the larval midgut.

Bayesian phylogeography of the Arawak expansion in lowland South America.

Phylogenetic inference based on language is a vital tool for tracing the dynamics of human population expansions. The timescale of agriculture-based expansions around the world provides an informative amount of linguistic change ideal for reconstructing phylogeographies. Here we investigate the expansion of Arawak, one of the most widely dispersed language families in the Americas, scattered from the Antilles to Argentina. It has been suggested that Northwest Amazonia is the Arawak homeland based on the large number of diverse languages in the region. We generate language trees by coding cognates of basic vocabulary words for 60 Arawak languages and dialects to estimate the phylogenetic relationships among Arawak societies, while simultaneously implementing a relaxed random walk model to infer phylogeographic history. Estimates of the Arawak homeland exclude Northwest Amazonia and are bi-modal, with one potential homeland on the Atlantic seaboard and another more likely origin in Western Amazonia. Bayesian phylogeography better supports a Western Amazonian origin, and consequent dispersal to the Caribbean and across the lowlands. Importantly, the Arawak expansion carried with it not only language but also a number of cultural traits that contrast Arawak societies with other lowland cultures.

Observation of the h(c)(1P) Using e+ e- collisions above the DD threshold.

Using 586 pb(-1) of e+ e- collision data at E(c.m.) = 4170 MeV, produced at the Cornell Electron Storage Ring collider and collected with the CLEO-c detector, we observe the process e+ e- → π+ π- h(c)(1P). We measure its cross section to be 15.6±2.3±1.9±3.0 pb, where the third error is due to the external uncertainty on the branching fraction of ψ(2S) → π0 h(c)(1P), which we use for normalization. We also find evidence for e+ e- → ηh(c)(1P) at 4170 MeV at the 3σ level and see hints of a rise in the e+ e- → π+ π- h(c)(1P) cross section at 4260 MeV.

Featural versus configural face processing in a rare genetic disorder: Williams syndrome.

BACKGROUND: Williams syndrome (WMS) is a rare genetic disorder with an estimated prevalence of 1 in 20 000 live births. Among other characteristics, WMS has a distinctive cognitive profile with spared face processing and language skills that contrasts with impairment in the cognitive domains of spatial cognition, problem solving and planning. It remains unclear whether individuals with WMS process faces using a featural strategy that focuses on features or a configural strategy that takes into consideration the contour of a face and spatial relations between features. METHODS: To investigate face processing in WMS, the tasks specifically probe unfamiliar face matching by using a design that includes manipulations in face presentation (thatcherised and non-thatcherised), face orientation (upright and inverted) and face valence (happy and neutral expression) in a match-to-target face recognition design. The sample consisted of 20 participants with WMS, 10 participants with non-specific developmental delay (IQ-matched) and 10 normal control participants (chronological age-matched). RESULTS: Similar to normal controls, WMS performed best when faces were presented upright. The results show while the WMS group did not perform as well as their typically developing counterparts, they did significantly better than the IQ-matched developmentally delayed group. WMS did not show an accuracy advantage for inverted faces commonly understood as an index for featural face processing, nor did they perform better on thatcherised inverted face conditions whereby featural processing is forced. Furthermore, no accuracy advantage was observed for positively valenced (happy) faces in the WMS group. CONCLUSION: These results are consistent with previous work showing a configural face processing approach in WMS, a strategy that is also utilised by normal controls.

Measures of adiposity in two cohorts of Hawaiian school children.

BACKGROUND: Native Hawaiians have high rates of obesity and obesity-related diseases compared with non-Hawaiians in Hawaii, and the relation between this ethnic disparity in adiposity and socioeconomic status (SES) in children is unclear. AIM: The present study compared measures of adiposity in two cohorts of school children residing in the Hilo area of Hawaii and related these measures to parental reports of ethnicity, household income and parent educational attainment. SUBJECTS AND METHODS: All children in either Kindergarten (mean age 5.6 years) or third grade (mean age 8.7 years) in eight elementary schools in the Hilo area were invited to participate. A total of 125 children had anthropometric, bioelectric impedance and air displacement plethysmography measurements taken and their parents answered questions about household income, parental educational attainment and genealogical background that included ethnicity of ancestors. RESULTS: Boys and girls in both cohorts had stature approximately at the 50(th) percentile (Z-score = 0) of national samples (CDC data). Z-scores of BMI were elevated compared to the CDC reference curves, but were significantly higher in male Native Hawaiian children in the older cohort among whom nearly 50% had a BMI above the 95(th) percentile for age. In the younger cohort, there was no significant ethnic difference in adiposity measures. In the older cohort, Native Hawaiian boys had significantly higher adiposity measures than their classmates. Adiposity in third grade girls was significantly and inversely related to their father's educational attainment. Percentage of Hawaiian ancestry was not significantly related to adiposity measures. CONCLUSIONS: Ethnic disparity in adiposity among Native Hawaiians compared with non-Hawaiian age mates occurs after the age of 6 years, and is confined to males in this sample. For older girls, father's, but not mother's, educational attainment was inversely related to adiposity.

Positive Selection of Transcription Factors Is a Prominent Feature of the Evolution of a Plant Pathogenic Genus Originating in the Miocene.

Tests based on the dN/dS statistic are used to identify positive selection of nonsynonymous polymorphisms. Using these tests on alignments of all orthologs from related species can provide insights into which gene categories have been most frequently positively selected. However, longer alignments have more power to detect positive selection, creating a detection bias that could create misleading results from functional enrichment tests. Most studies of positive selection in plant pathogens focus on genes with specific virulence functions, with little emphasis on broader molecular processes. Furthermore, no studies in plant pathogens have accounted for detection bias due to alignment length when performing functional enrichment tests. To address these research gaps, we analyze 12 genomes of the phytopathogenic fungal genus Botrytis, including two sequenced in this study. To establish a temporal context, we estimated fossil-calibrated divergence times for the genus. We find that Botrytis likely originated 16-18 Ma in the Miocene and underwent continuous radiation ending in the Pliocene. An untargeted scan of Botrytis single-copy orthologs for positive selection with three different statistical tests uncovered evidence for positive selection among proteases, signaling proteins, CAZymes, and secreted proteins. There was also a strong overrepresentation of transcription factors among positively selected genes. This overrepresentation was still apparent after two complementary controls for detection bias due to sequence length. Positively selected sites were depleted within DNA-binding domains, suggesting changes in transcriptional responses to internal and external cues or protein-protein interactions have undergone positive selection more frequently than changes in promoter fidelity.