Genetic markers validate using the natural phenotypic characteristics of shed feathers to identify individual northern goshawks Accipiter gentilis

Acknowledgements We are grateful to S. Piertney for allowing access to laboratory facilities and to M. Wenzel, R. Ogden and G. Murray-Dickson for their advice on genetic methods. This research was partly funded by a Natural Environment Research Council studentship NE/J500148/1 to SH and by Natural Research Limited.Peer reviewedPublisher PD

Reliability and validity of a nutrition and physical activity environmental self-assessment for child care

<p>Abstract</p> <p>Background</p> <p>Few assessment instruments have examined the nutrition and physical activity environments in child care, and none are self-administered. Given the emerging focus on child care settings as a target for intervention, a valid and reliable measure of the nutrition and physical activity environment is needed.</p> <p>Methods</p> <p>To measure inter-rater reliability, 59 child care center directors and 109 staff completed the self-assessment concurrently, but independently. Three weeks later, a repeat self-assessment was completed by a sub-sample of 38 directors to assess test-retest reliability. To assess criterion validity, a researcher-administered environmental assessment was conducted at 69 centers and was compared to a self-assessment completed by the director. A weighted kappa test statistic and percent agreement were calculated to assess agreement for each question on the self-assessment.</p> <p>Results</p> <p>For inter-rater reliability, kappa statistics ranged from 0.20 to 1.00 across all questions. Test-retest reliability of the self-assessment yielded kappa statistics that ranged from 0.07 to 1.00. The inter-quartile kappa statistic ranges for inter-rater and test-retest reliability were 0.45 to 0.63 and 0.27 to 0.45, respectively. When percent agreement was calculated, questions ranged from 52.6% to 100% for inter-rater reliability and 34.3% to 100% for test-retest reliability. Kappa statistics for validity ranged from -0.01 to 0.79, with an inter-quartile range of 0.08 to 0.34. Percent agreement for validity ranged from 12.9% to 93.7%.</p> <p>Conclusion</p> <p>This study provides estimates of criterion validity, inter-rater reliability and test-retest reliability for an environmental nutrition and physical activity self-assessment instrument for child care. Results indicate that the self-assessment is a stable and reasonably accurate instrument for use with child care interventions. We therefore recommend the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) instrument to researchers and practitioners interested in conducting healthy weight intervention in child care. However, a more robust, less subjective measure would be more appropriate for researchers seeking an outcome measure to assess intervention impact.</p

Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors

Src-family kinases (SFKs) play important roles in human biology and are key drug targets as well. However, achieving selective inhibition of individual Src-family kinases is challenging due to the high similarity within the protein family. We describe rhodium(II) conjugates that deliver both potent and selective inhibition of Src-family SH3 domains. Rhodium(II) conjugates offer dramatic affinity enhancements due to interactions with specific and unique Lewis-basic histidine residues near the SH3 binding interface, allowing predictable, structure-guided inhibition of SH3 targets that are recalcitrant to traditional inhibitors. In one example, a simple metallopeptide binds the Lyn SH3 domain with 6 nM affinity and exhibits functional activation of Lyn kinase under biologically relevant concentrations (EC50 ∼ 200 nM)

Diluting education? An ethnographic study of change in an Australian Ministry of Education

This ethnographic study captures the processes that led to change in an Australian public education system. The changes were driven by strong neo-liberal discourses which resulted in a shift from a shared understanding about leading educational change in schools by knowledge transfer to managing educational change as a process, in other words, allowing the schools to decide how to change. Inside an Australian state education bureaucracy at a time when the organisation was restructured and services decentralised, this study helps show some of the disturbing trends resulting from the further entrenchment of neo-liberal strategies. Although control was re-centralised by legitimising performance mechanisms, in the form of national testing, there are indications that the focus on national tests may have alarming consequences for the content and context of education. I argue that the complexities of learning and fundamental pedagogies are being lost in preference for an over reliance on data systems that are based on a shallow and narrow set of standardised measures

Assessing Foods Offered to Children at Child-Care Centers Using the Healthy Eating Index-2005

The Healthy Eating Index-2005 (HEI-2005) has been applied primarily to assess the quality of individual-level diets, but was recently applied to environmental-level data. Currently, no studies have applied the HEI-2005 to foods offered in child-care settings. This cross-sectional study used the HEI-2005 to assess the quality of foods/beverages offered to preschool children (three-five years old) in child-care centers. Two days of dietary observations were conducted, and 120 children (six children per center) were observed, at 20 child-care centers in North Carolina between July 2005 and January 2006. Data were analyzed between July 2011 and January 2012 using t-tests. The mean total HEI-2005 score (59.12) was significantly (p<0.01) lower than the optimal score of 100, indicating the need to improve the quality of foods offered to children. All centers met the maximum score for milk. A majority also met the maximum scores for total fruit (17 of 20 centers), whole fruit (15 of 20 centers), and sodium (19 of 20 centers). Mean scores for total vegetable (mean=2.26±1.09), dark green/orange vegetables and legumes (mean=0.20±0.43), total grain (mean=1.09±1.25), whole grain (mean=1.29±1.65), oils (mean=0.44±0.25), and meat/beans (mean=0.44±0.25) were significantly (p<0.01) lower than the maximum scores recommended. Mean scores for saturated fat (mean=3.32±3.41; p<0.01), and calories from solid fats and added sugars (mean=14.76±4.08; p<0.01) suggest the need to decrease the provision of foods high in these components. These findings indicate the need to improve the quality of foods offered to children at the centers to ensure that foods provided contribute to children’s daily nutrition requirements

Comparison of Menus to Actual Foods and Beverages Served in North Carolina Child-Care Centers

Menus from child-care centers are an important source of information for parents, researchers, and child-care regulators, but previous research suggests that menus do not accurately represent foods served. The purpose of this study was to compare menus with actual foods and beverages served to children in child-care centers. Menus were collected and a dietary observation was conducted to document all foods and beverages served to children during the course of 1 day in 84 child-care centers in North Carolina in the fall of 2005. Frequencies of foods and beverages on the menus vs those served were computed by eating occasion, food category, and individual foods and beverages. Of the 254 meals and snacks served, 131 (52%) meals and snacks matched entirely what was stated on the menu. Of the 820 individual foods and beverages served, 710 (86.6%) matched those listed on the menus. An additional 110 foods and beverages were served but not listed on the menus. Grains, juice, and vegetables were served less often than indicated on the menus, and milk, protein-rich foods, fruits, mixed dishes, and foods of low nutritional value were served more often than listed on the menus. Overall, just over half of all meals and snacks matched menus, and nearly 90% of individual foods and beverages served matched those stated on menus. Parents of children in child care and dietetics practitioners providing consultation to child-care centers can encourage not only provision of healthy foods and beverages, but also accurate menus in child care

Anti-tumour necrosis factor therapy for Dupuytren's Disease: a randomised dose response proof of concept phase 2a clinical trial

Background Dupuytren's disease is a common fibrotic condition of the hand that causes irreversible flexion contractures of the fingers, with no approved therapy for early stage disease. Our previous analysis of surgically-excised tissue defined tumour necrosis factor (TNF) as a potential therapeutic target. Here we assessed the efficacy of injecting nodules of Dupuytren's disease with a TNF inhibitor. Methods Patients were randomised to receive adalimumab on one occasion in dose cohorts of 15 mg in 0.3 ml, 35 mg in 0.7 ml, or 40 mg in 0.4 ml, or an equivalent volume of placebo in a 3:1 ratio. Two weeks later the injected tissue was surgically excised and analysed. The primary outcome measure was levels of mRNA expression for α-smooth muscle actin (ACTA2). Secondary outcomes included levels of α-SMA and collagen proteins. The trial was registered with ClinicalTrial.gov (NCT03180957) and the EudraCT (2015-001780-40). Findings We recruited 28 patients, 8 assigned to the 15 mg, 12 to the 35 mg and 8 to the 40 mg adalimumab cohorts. There was no change in mRNA levels for ACTA2, COL1A1, COL3A1 and CDH11. Levels of α-SMA protein expression in patients treated with 40 mg adalimumab (1.09 ± 0.09 ng per μg of total protein) were significantly lower (p = 0.006) compared to placebo treated patients (1.51 ± 0.09 ng/μg). The levels of procollagen type I protein expression were also significantly lower (p < 0.019) in the sub group treated with 40 mg adalimumab (474 ± 84 pg/μg total protein) compared with placebo (817 ± 78 pg/μg). There were two serious adverse events, both considered unrelated to the study drug. Interpretation In this dose-ranging study, injection of 40 mg of adalimumab in 0.4 ml resulted in down regulation of the myofibroblast phenotype as evidenced by reduction in expression of α-SMA and type I procollagen proteins at 2 weeks. These data form the basis of an ongoing phase 2b clinical trial assessing the efficacy of intranodular injection of 40 mg adalimumab in 0.4 ml compared to an equivalent volume of placebo in patients with early stage Dupuytren's disease

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define