Understanding the relative importance of vertical and horizontal flow in ice-wedge polygons

Ice-wedge polygons are common Arctic landforms. The future of these landforms in a warming climate depends on the bidirectional feedback between the rate of ice-wedge degradation and changes in hydrological characteristics. This work aims to better understand the relative roles of vertical and horizontal water fluxes in the subsurface of polygonal landscapes, providing new insights and data to test and calibrate hydrological models. Field-scale investigations were conducted at an intensively instrumented location on the Barrow Environmental Observatory (BEO) near Utqiagvik, AK, USA. Using a conservative tracer, we examined controls of microtopography and the frost table on subsurface flow and transport within a low-centered and a high-centered polygon. Bromide tracer was applied at both polygons in July 2015 and transport was monitored through two thaw seasons. Sampler arrays placed in polygon centers, rims, and troughs were used to monitor tracer concentrations. In both polygons, the tracer first infiltrated vertically until encountering the frost table and was then transported horizontally. Horizontal flow occurred in more locations and at higher velocities in the low-centered polygon than in the high-centered polygon. Preferential flow, influenced by frost table topography, was significant between polygon centers and troughs. Estimates of horizontal hydraulic conductivity were within the range of previous estimates of vertical conductivity, highlighting the importance of horizontal flow in these systems. This work forms a basis for understanding complexity of flow in polygonal landscapes

Protocol for: Sheffield Obesity Trial (SHOT): A randomised controlled trial of exercise therapy and mental health outcomes in obese adolescents [ISRCNT83888112]

Background While obesity is known to have many physiological consequences, the psychopathology of this condition has not featured prominently in the literature. Cross-sectional studies have indicated that obese children have increased odds of experiencing poor quality of life and mental health. However, very limited trial evidence has examined the efficacy of exercise therapy for enhancing mental health outcomes in obese children, and the Sheffield Obesity Trial (SHOT) will provide evidence of the efficacy of supervised exercise therapy in obese young people aged 11–16 years versus usual care and an attention-control intervention. Method/design SHOT is a randomised controlled trial where obese young people are randomised to receive; (1) exercise therapy, (2) attention-control intervention (involving body-conditioning exercises and games that do not involve aerobic activity), or (3) usual care. The exercise therapy and attention-control sessions will take place three times per week for eight weeks and a six-week home programme will follow this. Ninety adolescents aged between 11–16 years referred from a children's hospital for evaluation of obesity or via community advertisements will need to complete the study. Participants will be recruited according to the following criteria: (1) clinically obese and aged 11–16 years (Body Mass Index Centile > 98th UK standard) (2) no medical condition that would restrict ability to be active three times per week for eight weeks and (3) not diagnosed with insulin dependent diabetes or receiving oral steroids. Assessments of outcomes will take place at baseline, as well as four (intervention midpoint) and eight weeks (end of intervention) from baseline. Participants will be reassessed on outcome measures five and seven months from baseline. The primary endpoint is physical self-perceptions. Secondary outcomes include physical activity, self-perceptions, depression, affect, aerobic fitness and BMI

Intra-gastric balloon as an adjunct to lifestyle support in severely obese adolescents; Impact on weight, physical activity, cardio-respiratory fitness and psychosocial wellbeing.

BACKGROUND: Severe adolescent obesity (BMI>99.6th centile) is a significant public health challenge. Current non-invasive treatments, including community-based lifestyle interventions, are often of limited effectiveness in this population, with NICE guidelines suggesting the use of bariatric surgery as the last line of treatment (NICE, 2013). Health professionals are understandably reluctant to commission bariatric surgery and as an alternative, the use of an intra-gastric balloon as an adjunct to a lifestyle programme might offer a reversible, potentially safer and less invasive option. OBJECTIVES: Explore the use of an intra-gastric balloon as an adjunct to a lifestyle support programme, to promote weight loss in severely obese adolescents. Outcomes included Weight loss, Waist and Hip measurements, psychosocial outcomes including health related quality of life and physical self-perceptions, physical activity and cardiorespiratory fitness. METHOD: Non-randomised pilot study. Results: 12 severely obese adolescents (5 males, 7 females; mean age 15yrs; BMI >3.5 s.d.; puberty stage 4 or more) and their families were recruited. Mean weight loss at 12 months (n=9) was 3.05 kg±14.69; d=0.002, P=0.550, and a BMI Z-score (n=12) change of 0.2 s.d.; d=0.7, P=0.002 was observed at 6 months with a large effect, but was not sustained at 12 months (mean change 0.1 s.d.; d=0.3, P=0.146 ) At 24 months (n=10) there was a weight gain from baseline of +9.9 kg±1.21 (d=0.4; P=0.433). Adolescent and parent HRQoL scores exceeded the minimal clinical important difference between baseline and 12 months for all domains but showed some decline at 24 months. CONCLUSION: An intra-gastric balloon as an adjunct to a lifestyle support programme represents a safe and well tolerated treatment approach in severely obese adolescents, with short-term effects on weight change. Improvements in psychosocial health, physical activity and cardiorespiratory fitness were maintained at 12 months, with varying results at 24 months

Differential sensitivity of Src-family kinases to activation by SH3 domain displacement

Src-family kinases (SFKs) are non-receptor protein-tyrosine kinases involved in a variety of signaling pathways in virtually every cell type. The SFKs share a common negative regulatory mechanism that involves intramolecular interactions of the SH3 domain with the PPII helix formed by the SH2-kinase linker as well as the SH2 domain with a conserved phosphotyrosine residue in the C-terminal tail. Growing evidence suggests that individual SFKs may exhibit distinct activation mechanisms dictated by the relative strengths of these intramolecular interactions. To elucidate the role of the SH3:linker interaction in the regulation of individual SFKs, we used a synthetic SH3 domain-binding peptide (VSL12) to probe the sensitivity of downregulated c-Src, Hck, Lyn and Fyn to SH3-based activation in a kinetic kinase assay. All four SFKs responded to VSL12 binding with enhanced kinase activity, demonstrating a conserved role for SH3:linker interaction in the control of catalytic function. However, the sensitivity and extent of SH3-based activation varied over a wide range. In addition, autophosphorylation of the activation loops of c-Src and Hck did not override regulatory control by SH3:linker displacement, demonstrating that these modes of activation are independent. Our results show that despite the similarity of their downregulated conformations, individual Src-family members show diverse responses to activation by domain displacement which may reflect their adaptation to specific signaling environments in vivo. © 2014 Moroco et al

Azithromycin in the extremely low birth weight infant for the prevention of Bronchopulmonary Dysplasia: a pilot study

<p>Abstract</p> <p>Background</p> <p>Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (≤ 1000 grams) population.</p> <p>Methods</p> <p>Infants ≤ 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV) and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA.</p> <p>Results</p> <p>A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and birth weight were similar between groups. Mortality, incidence of BPD, days of IMV, and other morbidities were not significantly different between groups. Post-natal steroid use was significantly less in the treatment group [31% (6/19)] vs. placebo group [62% (10/16)] (p = 0.05). Duration of mechanical ventilation was significantly less in treatment survivors, with a median of 13 days (1–47 days) vs. 35 days (1–112 days)(p = 0.02).</p> <p>Conclusion</p> <p>Our study suggests that azithromycin prophylaxis in extremely low birth weight infants may effectively reduce post-natal steroid use for infants. Further studies are needed to assess the effects of azithromycin on the incidence of BPD and possible less common side effects, before any recommendations regarding routine clinical use can be made.</p

Understanding the Relative Importance of Vertical and Horizontal Flow in Ice-Wedge Polygons

Abstract. Ice-wedge polygons are common Arctic landforms. The future of these landforms in a warming climate depends on the bidirectional feedback between the rate of ice-wedge degradation and changes in hydrological characteristics. This work aims to better understand the relative roles of vertical and horizontal water fluxes in the subsurface of polygonal landscapes, providing new insights and data to test and calibrate hydrology models. Field-scale investigations were conducted at an intensively-instrumented location on the Barrow Environmental Observatory (BEO) near Utqiaġvik, AK, USA. Using a conservative tracer, we examined controls of microtopography and the frost table on subsurface flow and transport within a low-centered and a high-centered polygon. Bromide tracer was applied at both polygons in July 2015 and transport was monitored through two thaw seasons. Samplers arrays placed in polygon centers, rims, and troughs were used to monitor tracer concentrations. In both polygons, the tracer first infiltrated vertically until encountering the frost table, then was transported horizontally. Horizontal flow occurred in more locations and at higher velocities of fluxes in the low-centered polygon than in the high-centered polygon. Preferential flow, influenced by frost table topography, was significant between polygon centers and troughs. Estimates of horizontal hydraulic conductivity were within the range of previous estimates of vertical conductivity, highlighting the importance of horizontal flow in these systems. This work forms a basis for understanding complexity of flow in polygonal landscapes