Effects of human recombinant growth hormone on exercise capacity, cardiac structure, and cardiac function in patients with adult-onset growth hormone deficiency

Objective Epidemiological studies suggest that adult-onset growth hormone deficiency (AGHD) might increase the risk of death from cardiovascular causes. Methods This was a 6-month double-blind, placebo-controlled, randomised, cross-over trial followed by a 6-month open-label phase. Seventeen patients with AGHD received either recombinant human growth hormone (rGH) (0.4 mg injection daily) or placebo for 12 weeks, underwent washout for 2 weeks, and were then crossed over to the alternative treatment for a further 12 weeks. Cardiac magnetic resonance imaging, echocardiography, and cardiopulmonary exercise testing were performed at baseline, 12 weeks, 26 weeks, and the end of the open phase (12 months). The results were compared with those of 16 age- and sex-matched control subjects. Results At baseline, patients with AGHD had a significantly higher systolic blood pressure, ejection fraction, and left ventricular mass than the control group, even when corrected for body surface area. Treatment with rGH normalised the insulin-like growth factor 1 concentration without an effect on exercise capacity, cardiac structure, or cardiac function. Conclusion Administration of rGH therapy for 6 to 9 months failed to normalise the functional and structural cardiac differences observed in patients with AGHD when compared with a control group

In-situ strain softening and strain hardening of natural geomaterials on the microscale

Gas shale has proven to be a good candidate for mechanical characterization using nanoindentation. However, this natural material composed of nano-granular clay and microscale non-clay minerals also includes within its matrix a polymeric material. This kerogen biopolymer is interbedded and intertwined with the clay and non-clay minerals at almost all scales. Figure 1(a) demonstrates the nature of interlacing that occurs between shale rock and organic matter. Kerogen within the shale matrix has been mechanically characterized using nanoindentation to determine Young’s modulus and hardness such as in the work by Zeszotarski et al. 2004. As a polymer kerogen not only has a Young’s modulus in compression but also has a substantial Young’s modulus value in tension and much higher tensile strength than rocks in general! This fact has now been observed at the micro- and nanoscale during nanoindentation while monitoring in situ via scanning electron microscopy (SEM). Load and unload experiments with micro-Newton forces (µN) and nanometer (nm) displacements have clearly shown the elastic nature of kerogen in the shale gas matrix. This unique experimental setup provided us not only the ability to load and fracture micro- and nano-scale kerogen-rich shale structures but also the advantage of visualizing the initiation, propagation, and ultimate failure of the beams. Subsequent high resolution imaging of the support and beam fracture faces as well as complementary EDS allowed us to analyze the grains/minerals and non-minerals associated with the fracture. Strain softening behavior was measured on this composite at the micro scale in cantilever micro-beam as shown in Figure 1 (b) and (c). This behavior of gas shale could never be captured at the macro-scale

Prevalence and correlates of physical activity across kidney disease stages: an observational multicentre study

Background: People with chronic kidney disease (CKD) report high levels of physical inactivity, a major modifiable risk factor for morbidity and mortality. Understanding the biological, psychosocial and demographic causes of physical activity behaviour is essential for the development and improvement of potential health interventions and promotional initiatives. This study investigated the prevalence of physical inactivity and determined individual correlates of this behaviour in a large sample of patients across the spectrum of kidney disease. / Methods: A total of 5656 people across all stages of CKD (1–2, 3, 4–5, haemodialysis, peritoneal dialysis and renal transplant recipients) were recruited from 17 sites in England from July 2012 to October 2018. Physical activity was evaluated using the General Practice Physical Activity Questionnaire. Self-reported cardiorespiratory fitness, self-efficacy and stage of change were also assessed. Binominal generalized linear mutually adjusted models were conducted to explore the associations between physical activity and correlate variables. This cross-sectional observational multi-centre study was registered retrospectively as ISRCTN87066351 (October 2015). / Results: The prevalence of physical activity (6–34%) was low and worsened with disease progression. Being older, female and having a greater number of comorbidities were associated with greater odds of being physically inactive. Higher haemoglobin, cardiorespiratory fitness and self-efficacy levels were associated with increased odds of being active. Neither ethnicity nor smoking history had any effect on physical activity. / Conclusions: Levels of physical inactivity are high across all stages of CKD. The identification of stage-specific correlates of physical activity may help to prioritize factors in target groups of kidney patients and improve the development and improvement of public health interventions

Unoriented D-brane instantons

We give a pedagogical introduction to D-brane instanton effects in vacuum configurations with open and unoriented strings. We focus on quiver gauge theories for unoriented D-branes at orbifold singularities and describe in some detail the Z_3 case, where both `gauge' and `exotic' instantons can generate non-perturbative super potentials, and the Z_5 case, where supersymmetry breaking may arise from the combined effect of `gauge' instantons and a FI D-term.Comment: 12 pages, 1 figure. Proceedings of the "XVII European Workshop on String Theory 2011", Padova, Italy, 5-9 September 201

Can simple rules control development of a pioneer vertebrate neuronal network generating behavior?

How do the pioneer networks in the axial core of the vertebrate nervous system first develop? Fundamental to understanding any full-scale neuronal network is knowledge of the constituent neurons, their properties, synaptic interconnections, and normal activity. Our novel strategy uses basic developmental rules to generate model networks that retain individual neuron and synapse resolution and are capable of reproducing correct, whole animal responses. We apply our developmental strategy to young Xenopus tadpoles, whose brainstem and spinal cord share a core vertebrate plan, but at a tractable complexity. Following detailed anatomical and physiological measurements to complete a descriptive library of each type of spinal neuron, we build models of their axon growth controlled by simple chemical gradients and physical barriers. By adding dendrites and allowing probabilistic formation of synaptic connections, we reconstruct network connectivity among up to 2000 neurons. When the resulting "network" is populated by model neurons and synapses, with properties based on physiology, it can respond to sensory stimulation by mimicking tadpole swimming behavior. This functioning model represents the most complete reconstruction of a vertebrate neuronal network that can reproduce the complex, rhythmic behavior of a whole animal. The findings validate our novel developmental strategy for generating realistic networks with individual neuron- and synapse-level resolution. We use it to demonstrate how early functional neuronal connectivity and behavior may in life result from simple developmental "rules," which lay out a scaffold for the vertebrate CNS without specific neuron-to-neuron recognition

Handwriting-Based Gender Classification Using End-to-End Deep Neural Networks

Handwriting-based gender classification is a well-researched problem that has been approached mainly by traditional machine learning techniques. In this paper, we propose a novel deep learning-based approach for this task. Specifically, we present a convolutional neural network (CNN), which performs automatic feature extraction from a given handwritten image, followed by classification of the writer's gender. Also, we introduce a new dataset of labeled handwritten samples, in Hebrew and English, of 405 participants. Comparing the gender classification accuracy on this dataset against human examiners, our results show that the proposed deep learning-based approach is substantially more accurate than that of humans

Exploring patterns of recurrent melanoma in Northeast Scotland to inform the introduction a digital self-examination intervention

Peer reviewedPublisher PD

Sovereign credit ratings and financial markets linkages: application to European data

We use EU sovereign bond yield and CDS spreads daily data to carry out an event study analysis on the reaction of government yield spreads before and after announcements from rating agencies (Standard & Poor’s, Moody’s, Fitch). Our results show significant responses of government bond yield spreads to changes in rating notations and outlook, particularly in the case of negative announcements. Announcements are not anticipated at 1-2 months horizon but there is bi-directional causality between ratings and spreads within 1-2 weeks; spillover effects especially among EMU countries and from lower rated countries to higher rated countries; and persistence effects for recently downgraded countries

Fibrin glue for pilonidal sinus disease

Background Pilonidal sinus disease is a common condition that mainly affects young adults. This condition can cause significant pain and impairment of normal activities. No consensus currently exists on the optimum treatment for pilonidal sinus and current therapies have various advantages and disadvantages. Fibrin glue has emerged as a potential treatment as both monotherapy and an adjunct to surgery. Objectives To assess the effects of fibrin glue alone or in combination with surgery compared with surgery alone in the treatment of pilonidal sinus disease. Search methods In December 2016 we searched: the Cochrane Wounds Specialised Register; CENTRAL; MEDLINE; Embase and CINAHL Plus. We also searched clinical trials registries and conference proceedings for ongoing and unpublished studies and scanned reference lists to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. Selection criteria We included randomised controlled trials (RCTs) only. We included studies involving participants of all ages and studies conducted in any setting. We considered studies involving people with both new and recurrent pilonidal sinus. We included studies which evaluated fibrin glue monotherapy or as an adjunct to surgery. Data collection and analysis Two study authors independently extracted data and assessed risk of bias. We used standard methods expected by Cochrane. Main results We included four RCTs with 253 participants, all were at risk of bias. One unpublished study evaluated fibrin glue monotherapy compared with Bascom's procedure, two studies evaluated fibrin glue as an adjunct to Limberg flap and one study evaluated fibrin glue as an adjunct to Karydakis flap. For fibrin glue monotherapy compared with Bascom's procedure, there were no data available for the primary outcomes of time to healing and adverse events. There was low-quality evidence of less pain on day one after the procedure with fibrin glue monotherapy compared with Bascom's procedure (mean difference (MD) -2.50, 95% confidence interval (CI) -4.03 to -0.97) (evidence downgraded twice for risk of performance and detection bias). Fibrin glue may reduce the time taken to return to normal activities compared with Bascom's procedure (mean time 42 days with surgery and 7 days with glue, MD -34.80 days, 95% CI -66.82 days to -2.78 days) (very low-quality evidence, downgraded as above and for imprecision). Fibrin glue as an adjunct to the Limberg flap may reduce the healing time from 22 to 8 days compared with the Limberg flap alone (MD -13.95 days, 95% CI -16.76 days to -11.14 days) (very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and imprecision). It is uncertain whether use of fibrin glue affects the incidence of postoperative seroma (an adverse event) (risk ratio (RR) 0.27, 95% CI 0.05 to 1.61; very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and imprecision). There was low-quality evidence that fibrin glue, as an adjunct to Limberg flap, may reduce postoperative pain (median 2 versus 4; P < 0.001) and time to return to normal activities (median 8 days versus 17 days; P < 0.001). The addition of fibrin glue to the Limberg flap may reduce the length of hospital stay (MD -1.69 days, 95% CI -2.08 days to -1.29 days) (very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and for unexplained heterogeneity). A single RCT evaluating fibrin glue as an adjunct to the Karydakis flap did not report data for the primary outcome of time to healing. It is uncertain whether fibrin glue with the Karydakis flap affects the incidence of postoperative seroma (adverse event) (RR 3.00, 95% CI 0.67 to 13.46) (very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and for imprecision). Fibrin glue as an adjunct to Karydakis flap may reduce length of stay but this is highly uncertain (mean 2 days versus 3.7 days; P < 0.001, low-quality evidence downgraded twice for risk of selection, performance and detection bias). Authors' conclusions Current evidence is uncertain regarding any benefits associated with fibrin glue either as monotherapy or as an adjunct to surgery for people with pilonidal sinus disease. We identified only four RCTs and each was small and at risk of bias resulting in very low-quality evidence for the primary outcomes of time to healing and adverse events. Future studies should enrol many more participants, ensure adequate randomisation and blinding, whilst measuring clinically relevant outcomes