bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced peripheral activity leading to hepato‐preferential action of basal insulin peglispro compared with insulin glargine in patients with type 1 diabetes
Authors: Mudaliar S. , Henry R. R. , Ciaraldi T. P. , Armstrong D. A. , Burke P. M. , Pettus J. H. , Garhyan P. , Choi S. L. , Knadler M. P. , Lam E. C. Q. , Prince M. J. , Bose N. , Porksen N. K. , Sinha V. P. , Linnebjerg H. , Jacober S. J. 
Published: October 2016

AimsBasal insulin peglispro (BIL), a novel PEGylated basal insulin with a large hydrodynamic size, has a delayed absorption and reduced clearance that prolongs the duration of action. The current study compared the effects of BIL and insulin glargine (GL) on endogenous glucose production (EGP), glucose disposal rate (GDR) and lipolysis in patients with type 1 diabetes.Materials and MethodsThis was a randomized, open‐label, four‐period, crossover study. Patients received intravenous infusions of BIL and GL, each at two dose levels selected for partial and maximal suppression of EGP, during an 8 to 10 h euglycemic clamp procedure with d‐[3‐3H] glucose.ResultsFollowing correction for equivalent human insulin concentrations (EHIC), low‐dose GL infusion resulted in similar EGP at the end of the clamp compared to low‐dose BIL infusion (GL/BIL ratio of 1.03) but a higher GDR (GL/BIL ratio of 2.42), indicating similar hepatic activity but attenuated peripheral activity of BIL. Consistent with this, the EHIC‐corrected GDR/EGP at the end of the clamp was 1.72‐fold greater for GL than BIL following low‐dose administration. At the lower dose of BIL and GL (concentrations in the therapeutic range), BIL produced less suppression of lipolysis compared with GL as indicated by free fatty acid and glycerol levels at the end of the clamp.ConclusionsCompared with GL, BIL restored the hepato‐peripheral insulin action gradient seen in normal physiology via its peripherally restricted action on target tissues related to carbohydrate and lipid metabolism.
A meta‐analysis comparing clinical effects of short‐ or long‐acting GLP‐1 receptor agonists versus insulin treatment from head‐to‐head studies in type 2 diabetic patients
Authors: Abd El Aziz Mirna S. , Kahle Melanie , Meier Juris J. , Nauck Michael A. 
Published: October 2016

AimsTo study differences in clinical outcomes between initiating glucagon‐like peptide‐1 receptor agonist (GLP‐1 RAs) vs insulin treatment in patients with type 2 diabetes treated with oral glucose‐lowering medications (OGLM).MethodsProspective, randomized trials comparing GLP‐1 RA and insulin treatment head‐to‐head as add‐on to OGLM were identified (PubMed). Differences from baseline values were compared for HbA1c, fasting plasma glucose, bodyweight, blood pressure, heartrate and lipoproteins. Proportions of patients reporting hypoglycaemic episodes were compared.ResultsOf 712 publications identified, 23 describing 19 clinical trials were included in the meta‐analysis. Compared to insulin, GLP‐1 RAs reduced HbA1c more effectively (Δ −.12%,
P
< .0001). Basal insulin was more effective in reducing fasting plasma glucose (Δ −1.8 mmol/L,
P
< .0001). GLP‐1 RAs reduced bodyweight more effectively (Δ −3.71 kg;
P
< .0001). The proportion of patients experiencing hypoglycaemic episodes was 34% lower with GLP‐1 RAs (
P
< .0001), with a similar trend for severe hypoglycaemia. Systolic blood pressure was lower and heartrate was higher with GLP‐1 RAs (
P
< .0001). Triglycerides and LDL cholesterol were significantly lower with GLP‐1 RAs. Long‐acting GLP‐1 RAs were better than short‐acting GLP‐1 RAs in reducing HbA1c and fasting glucose, but were similar regarding bodyweight.ConclusionsSlightly better glycaemic control can be achieved by adding GLP‐1 RAs to OGLM as compared to insulin treatment, with added benefits regarding bodyweight, hypoglycaemia, blood pressure and lipoproteins. These differences are in contrast to the fact that insulin is prescribed far more often than GLP‐1 RAs.
Observational research rigour alone does not justify causal inference
Authors: Ejima Keisuke , Li Peng , Smith Daniel L. , Nagy Tim R. , Kadish Inga , van Groen Thomas , Dawson John A. , Yang Yongbin , Patki Amit , Allison David B. 
Published: October 2016

AbstractBackgroundDiffering opinions exist on whether associations obtained in observational studies can be reliable indicators of a causal effect if the observational study is sufficiently well controlled and executed.Materials and methodsTo test this, we conducted two animal observational studies that were rigorously controlled and executed beyond what is achieved in studies of humans. In study 1, we randomized 332 genetically identical C57BL/6J mice into three diet groups with differing food energy allotments and recorded individual self‐selected daily energy intake and lifespan. In study 2, 60 male mice (CD1) were paired and divided into two groups for a 2‐week feeding regimen. We evaluated the association between weight gain and food consumption. Within each pair, one animal was randomly assigned to an S group in which the animals had free access to food. The second paired animal (R group) was provided exactly the same diet that their S partner ate the day before.ResultsIn study 1, across all three groups, we found a significant negative effect of energy intake on lifespan. However, we found a positive association between food intake and lifespan among the ad libitum feeding group: 29·99 (95% CI: 8·2–51·7) days per daily kcal. In study 2, we found a significant (P = 0·003) group (randomized vs. self‐selected)‐by‐food consumption interaction effect on weight gain.ConclusionAt least in nutrition research, associations derived from observational studies may not be reliable indicators of causal effects, even with the most rigorous study designs achievable.
First‐episode psychosis: Ongoing mental health service utilization during the stable period for adolescents
Authors: Gearing Robin E. , Brewer Kathryne B. , Mian Irfan , Moore Kiara , Fisher Prudence , Hamilton Jane , Mandiberg James 
Published: October 2016

AbstractAimThe timely identification and treatment of psychosis are increasingly the focus of early interventions, with research targeting the initial high‐risk period in the months following first‐episode hospitalization. Ongoing treatment after stabilization is also essential in the years following a first‐episode psychosis (FEP), but has received less research attention. In this study, variables that could impact continued psychiatric service utilization by adolescents following their FEP and temporal patterns in service utilization are examined.MethodsFamilies of 52 adolescents (aged 14.4 ± 2.5 years) discharged following a hospitalization for FEP were contacted two or more years following the adolescents’ discharge. A chart review (Time 1) of hospital records provided clinical data on each adolescent's psychiatric diagnosis, symptoms, illness course, medications and family history. Follow‐up (Time 2) data were collected from parents/caregivers using a questionnaire enquiring about post‐discharge treatment history and service utilization.ResultsBivariate analyses were conducted to identify Time 1 variables associated with psychiatric service utilization at Time 2. Significant variables were included in a logistic regression model and three variables were independently associated with continued service utilization: having a primary diagnosis of schizophrenia (odds ratio (OR) = 24.0; P = 0.02), not having a first‐degree relative with depression (OR = 0.12; P = 0.05) and fewer months since the last inpatient discharge (OR = 0.92; P = 0.02).ConclusionsFindings suggest: (1) the importance of early diagnosis, (2) that a relative with depression may negatively influence the adolescent's ongoing service utilization, and (3) that 18 months post‐discharge may be a critical time to review treatment strategies and collaborate with youth and families to ensure appropriateness of services.
Predictors of functioning in people suffering from first‐episode psychosis 1 year into entering early intervention service in Hong Kong
Authors: Chong Catherine Shiu‐yin , Siu Man‐Wah , Kwan Condy Hoi‐shuen , Chang Wing‐Chung , Lee Edwin Ho‐ming , Chan Sherry Kit‐wa , Hui Christy Lai‐ming , Tam Fiona Yee‐ki , Chen Eric Yu‐hai , Lo William Tak‐lam 
Published: October 2016

AbstractAimTo explore the changes of functioning in people suffering from first‐episode psychosis throughout their first year into an early intervention service, and the baseline predictors of their functioning levels at baseline, 6 and 12 monthsMethodConsecutive subjects presenting to an early intervention service were recruited from 1 February 2013 to 31 May 2015. Information on their socio‐demographic status was collected. Structured instruments were used to assess their premorbid functioning, duration of untreated psychosis, psychopathology and insight at baseline. Psychosocial functioning was assessed by Social Occupational Functioning Assessment Scale (SOFAS) and Role Functioning Scale at baseline, 6 and 12 months.ResultsA total of 269 subjects were recruited. The mean baseline scores for SOFAS were 53.1 (standard deviation = 13.6) and 21.5 (standard deviation = 4.0), respectively. Positive and negative psychopathology, insight and mode of onset were significant factors associated with baseline functioning. Functioning by both instruments showed significant improvement after 6 months, and the gains were maintained at 12 months. For SOFAS, baseline insight (P = 0.008), education attainment (P = 0.016) and its own baseline score (P = 0.024) were predictive at 6 months, while for 12 months, only education attainment was predictive (P = 0.008). For Role Functioning Scale, its baseline score (P = 0.034) was predictive at 6 months, while at 12 months, only female gender predicted better role functioning.ConclusionFactors predictive of functioning levels at the three time points were different. Phase‐specific intervention should be offered to enhance functional recovery of people with first‐episode psychosis.
Complex Education Systems: from steering change to governance
Authors: Michel Alain 
Published: October 2016

AbstractThe theories and approaches of steering/monitoring a process of change within education systems have evolved over the last 20 years or so as a result of many factors such as globalisation and decentralisation, a faster pace of change, increasing expectations and demands from various stakeholders (parents, employers, teacher unions, etc.) and the growing influence of OECD and of the EU in the field of education because of some more or less explicit standards and policy recommendations. All these evolutions contributed to increase the complexity of the education systems and of the instruments and procedures required to establish some coherence between the initiatives of a large number of more autonomous stakeholders. Our main objective here is to describe how the previous notions and concepts used in analysing the conditions for steering education systems have been gradually integrated within a larger paradigm: the ‘governance of multi‐level complex education systems’.
Encoding of global visual motion in the nidopallium caudolaterale of behaving crows
Authors: Wagener Lysann , Nieder Andreas 
Published: October 2016

AbstractSongbirds possess acute vision. How higher brain centres represent basic and parameterised visual stimuli to process sensory signals according to their behavioural importance has not been studied in a systematic way. We therefore examined how carrion crows (Corvus corone) and their nidopallial visual neurons process global visual motion information in dynamic random‐dot displays during a delayed match‐to‐sample (DMS) task. The behavioural data show that moderately fast motion speeds (16° of visual angle/s) result in superior direction discrimination performance. To characterise how neurons encode and maintain task‐relevant visual motion information, we recorded the single‐unit activity in the telencephalic association area ‘nidopallium caudolaterale’ (NCL) of behaving crows. The NCL is considered to be the avian analogue of the mammalian prefrontal cortex. Almost a third (28%) of randomly selected NCL neurons responded selectively to the motion direction of the sample stimulus, mostly to downward motions. Only few NCL neurons (7.5%) responded consistently to specific motion directions during the delay period. In error trials, when the crows chose the wrong motion direction, the encoding of motion direction was significantly reduced. This indicates that sensory representations of NCL neurons are relevant to the birds’ behaviour. These data suggest that the corvid NCL, even though operating at the apex of the telencephalic processing hierarchy, constitutes a telencephalic site for global motion integration.
If Reason is ‘in the World’, Where Exactly is it Located?
Authors: Redding Paul 
Published: October 2016

AbstractIn his recent book James Kreines argues that for Hegel reason is “in the world”, but how we are to understand the idea of reason's being so located? One answer, suggested by more traditional theocentric readings of Hegel, would be to appeal to the idea of a divine thought, coursing through the world. Another answer, more congenial to modern sensibilities, might locate reason within the rational activities of inter‐subjectively connected human beings, as suggested by Terry Pinkard's idea of the “sociality of reason”. Kreines seems to want to avoid suggestions of the former, but in distancing himself from approaches like the latter, he also seems to refuse the more metaphysically modest alternative. In retracing the contours of Kreines's nuanced attempt to reinflate Hegel's metaphysics as a “metaphysics of reason”, I pose the question as to whether he can avoid reintroducing a more extravagantly metaphysical Hegel than he wishes.
Crop‐to‐wild gene flow and its fitness consequences for a wild fruit tree: Towards a comprehensive conservation strategy of the wild apple in Europe
Authors: Feurtey Alice , Cornille Amandine , Shykoff Jacqui A. , Snirc Alodie , Giraud Tatiana 
Published: October 2016

AbstractCrop‐to‐wild gene flow can reduce the fitness and genetic integrity of wild species. Malus sylvestris, the European crab‐apple fruit tree in particular, is threatened by the disappearance of its habitat and by gene flow from its domesticated relative, Malus domestica. With the aims of evaluating threats for M. sylvestris and of formulating recommendations for its conservation, we studied here, using microsatellite markers and growth experiments: (i) hybridization rates in seeds and trees from a French forest and in seeds used for replanting crab apples in agrosystems and in forests, (ii) the impact of the level of M. domestica ancestry on individual tree fitness and (iii) pollen dispersal abilities in relation to crop‐to‐wild gene flow. We found substantial contemporary crop‐to‐wild gene flow in crab‐apple tree populations and superior fitness of hybrids compared to wild seeds and seedlings. Using paternity analyses, we showed that pollen dispersal could occur up to 4 km and decreased with tree density. The seed network furnishing the wild apple reintroduction agroforestry programmes was found to suffer from poor genetic diversity, introgressions and species misidentification. Overall, our findings indicate supported threats for the European wild apple steering us to provide precise recommendations for its conservation.
High diversity of the T‐cell receptor repertoire of tumor‐infiltrating lymphocytes in basal cell carcinoma
Authors: Omland Silje H. , Hamrouni Abdelbasset , Gniadecki Robert 
Published: October 2016

AbstractWhether specific T‐cell clones are present in tumor infiltrating lymphocytes (TILs) in BCC is unknown. We employed deep sequencing of mRNA coding for the T‐cell receptor (TCR) chains α‐ and β to characterize the repertoire of TILs in BCC. V and J gene‐usage and CDR3 length were computed to determine the clonality of TCR and degree of overlap in TCR repertoires between skin resident T‐cells and TILs. We found high diversity of the TCR repertoire in BCC and control skin with random V‐J gene usage and similar CDR3‐length distribution. Lack of TCR repertoire restriction indicates absence of tumor‐specific TIL clones in BCC.
Nitrogen‐mediated effects of elevated CO2 on intra‐aggregate soil pore structure
Authors: Caplan Joshua S. , Giménez Daniel , Subroy Vandana , Heck Richard J. , Prior Stephen A. , Runion G. Brett , Torbert H. Allen 
Published: October 2016

AbstractSoil pore structure has a strong influence on water retention, and is itself influenced by plant and microbial dynamics such as root proliferation and microbial exudation. Although increased nitrogen (N) availability and elevated atmospheric CO2 concentrations (eCO2) often have interacting effects on root and microbial dynamics, it is unclear whether these biotic effects can translate into altered soil pore structure and water retention. This study was based on a long‐term experiment (7 yr at the time of sampling) in which a C4 pasture grass (Paspalum notatum) was grown on a sandy loam soil while provided factorial additions of N and CO2. Through an analysis of soil aggregate fractal properties supported by 3D microtomographic imagery, we found that N fertilization induced an increase in intra‐aggregate porosity and a simultaneous shift toward greater accumulation of pore space in larger aggregates. These effects were enhanced by eCO2 and yielded an increase in water retention at pressure potentials near the wilting point of plants. However, eCO2 alone induced changes in the opposite direction, with larger aggregates containing less pore space than under control conditions, and water retention decreasing accordingly. Results on biotic factors further suggested that organic matter gains or losses induced the observed structural changes. Based on our results, we postulate that the pore structure of many mineral soils could undergo N‐dependent changes as atmospheric CO2 concentrations rise, having global‐scale implications for water balance, carbon storage, and related rhizosphere functions.
Effects of ocean acidification increase embryonic sensitivity to thermal extremes in Atlantic cod, Gadus morhua
Authors: Dahlke Flemming T. , Leo Elettra , Mark Felix C. , Pörtner Hans‐Otto , Bickmeyer Ulf , Frickenhaus Stephan , Storch Daniela 
Published: October 2016

AbstractThermal tolerance windows serve as a powerful tool for estimating the vulnerability of marine species and their life stages to increasing temperature means and extremes. However, it remains uncertain to which extent additional drivers, such as ocean acidification, modify organismal responses to temperature. This study investigated the effects of CO2‐driven ocean acidification on embryonic thermal sensitivity and performance in Atlantic cod, Gadus morhua, from the Kattegat. Fertilized eggs were exposed to factorial combinations of two PCO2 conditions (400 μatm vs. 1100 μatm) and five temperature treatments (0, 3, 6, 9 and 12 °C), which allow identifying both lower and upper thermal tolerance thresholds. We quantified hatching success, oxygen consumption (MO2) and mitochondrial functioning of embryos as well as larval morphometrics at hatch and the abundance of acid–base‐relevant ionocytes on the yolk sac epithelium of newly hatched larvae. Hatching success was high under ambient spawning conditions (3–6 °C), but decreased towards both cold and warm temperature extremes. Elevated PCO2 caused a significant decrease in hatching success, particularly at cold (3 and 0 °C) and warm (12 °C) temperatures. Warming imposed limitations to MO2 and mitochondrial capacities. Elevated PCO2 stimulated MO2 at cold and intermediate temperatures, but exacerbated warming‐induced constraints on MO2, indicating a synergistic interaction with temperature. Mitochondrial functioning was not affected by PCO2. Increased MO2 in response to elevated PCO2 was paralleled by reduced larval size at hatch. Finally, ionocyte abundance decreased with increasing temperature, but did not differ between PCO2 treatments. Our results demonstrate increased thermal sensitivity of cod embryos under future PCO2 conditions and suggest that acclimation to elevated PCO2 requires reallocation of limited resources at the expense of embryonic growth. We conclude that ocean acidification constrains the thermal performance window of embryos, which has important implication for the susceptibility of cod to projected climate change.
Generation of paternal dihaploids in tall fescue
Authors: Kindiger Bryan 
Published: October 2016

AbstractWithin the Lolium‐Festuca genome complex there is a need for modern breeding approaches that can facilitate the rapid development of improved germplasm or cultivars. Traditional recurrent or mass‐selection methods for population or synthetic development are labor intensive and time consuming. The recent development of dihaploid (DH) inducer lines of annual ryegrass (Lolium perenne L. subsp. multiflorum (Lam.) Husnot [syn. Lolium multiflorum Lam.]) that exhibit genome loss when hybridized with tall fescue (Lolium arundinaceum (Schreb.) Darbysh. [syn. Festuca arundinacea Schreb.]) can provide an alternative breeding approach. Hybridizations between the inducer lines and tall fescue result in F1 hybrids that can lose either their ryegrass or tall fescue genomes. This behavior results in the occasional generation of both ryegrass and tall fescue DH lines through parthenogenic embryo formation within the F1 inflorescence.
RCT – subjective physical performance and quality of life after a 6‐month programmed sports therapy (PST) in patients with haemophilia
Authors: Runkel B. , Von Mackensen S. , Hilberg T. 
Published: October 2016

IntroductionMusculoskeletal bleedings lead to limitations in the locomotor system and consequently, in health‐related quality of life (HRQoL) in patients with haemophilia (PwH). Sports therapy is increasingly recommended to improve their physical performance. Until today, randomised controlled studies investigating changes in physical performance in PwH are rare.AimThis study investigates the impact of programmed sports therapy on the subjective physical performance and the HRQoL in PwH.MethodsA randomised controlled trial (RCT) was conducted with a training intervention for over 6 months. For this purpose, 64 PwH with moderate (n = 5) or severe (n = 59) haemophilia A (n = 57) or B (n = 7) were randomised into two groups – intervention (IG) or control group (CG). The HRQoL was assessed with the SF‐36 questionnaire and the disease‐specific Haem‐A‐QoL before and after the intervention. The subjective physical performance was tested by the HEP‐Test‐Q.ResultsAfter the 6‐month training intervention, PwH in the IG subjectively reported significant better ‘endurance’ (P = 0.000) in the HEP‐Test‐Q compared to the CG. In the SF‐36, a significant difference in the domains ‘general health perceptions’ (P = 0.005) and ‘mental health’ (P = 0.001) was detected. The haemophilia‐specific HRQoL questionnaire showed a significant improvement in the dimensions ‘feeling’ (P = 0.049), ‘work’ (P = 0.046) and ‘family’ (P = 0.040).ConclusionIn the first RCT evaluating the impact of a 6‐month training intervention on the subjective perception of PwH, an increase in subjective physical performance and some domains of HRQoL was demonstrated in the IG. Specific sports therapy should be included into the comprehensive treatment under supervision and monitoring by experienced staff.