bluuebunny/crossref_metadata_2025 huggingface dataset:
A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics
Authors: Pare Guillaume , Mao Shihong , Deng Wei Q.
Published: August 2015

Despite considerable efforts, known genetic associations only explain a small fraction of predicted heritability. Regional associations combine information from multiple contiguous genetic variants and can improve variance explained at established association loci. However, regional associations are not easily amenable to estimation using summary association statistics because of sensitivity to linkage disequilibrium (LD). We now propose a novel method to estimate phenotypic variance explained by regional associations using summary statistics while accounting for LD. Our method is asymptotically equivalent to multiple regression models when no interaction or haplotype effects are present. It has multiple applications, such as ranking of genetic regions according to variance explained or comparison of variance explained by to or more regions. Using height and BMI data from the Health Retirement Study (N=7,776), we show that most genetic variance lies in a small proportion of the genome and that previously identified linkage peaks have higher than expected regional variance.
DNA break-induced sumoylation is enabled by collaboration between a SUMO ligase and the ssDNA-binding complex RPA
Authors: Chung Inn , Zhao Xiaolan
Published: August 2015

Upon genome damage, large-scale protein sumoylation occurs from yeast to humans to promote DNA repair. Currently, the underlying mechanism is largely unknown. Here we show that, upon DNA break induction, the budding yeast SUMO ligase Siz2 collaborates with the ssDNA-binding complex RPA (replication protein A) to induce the sumoylation of recombination factors and confer damage resistance. Both RPA and nuclease-generated ssDNA promote Siz2-mediated sumoylation. Mechanistically, the conserved Siz2 interaction with RPA enables Siz2 localization to damage sites. These findings provide a molecular basis for recruiting SUMO ligases to the vicinity of their substrates to induce sumoylation upon DNA damage.
Temperature dependence of thermal expansion tensors of energetic materials
Authors: Bolotina Nadezhda B. , Pinkerton A. Alan
Published: August 2015

Unit-cell values as well as thermal expansion tensors for 13 energetic materials are calculated from variable-temperature X-ray diffraction data. The thermal expansion tensors and their temperature dependence are reported numerically, algebraically and graphically.
In situmonitoring of phase transformation microstructures at Earth's mantle pressure and temperature using multi-grain XRD
Authors: Rosa Angelika Dorothea , Hilairet Nadège , Ghosh Sujoy , Garbarino Gaston , Jacobs Jeroen , Perrillat Jean-Philippe , Vaughan Gavin , Merkel Sébastien
Published: August 2015

Microstructures govern the mechanical properties of materials and change dramatically during phase transformations. A detailed understanding of microstructures at different stages of a transformation is important for the design of new materials and for constraining geophysical processes. However, experimental studies of transformation microstructures at the grain scale have been mostly based onex situobservations of quenched products, which are difficult to correlate with bulk sample properties and transformation kinetics. Here, it is shown how multi-grain crystallography on polycrystalline samples, combined with a resistively heated diamond anvil cell, can be applied to investigate the microstructural properties of a material undergoing a phase transitionin situat high pressure and high temperature. This approach allows the extraction of the crystallographic parameters and orientations of several hundreds of grains inside a transforming sample. Important bulk information on grain size distributions and orientation relations between the parent and the newly formed phase at the different stages of the transformation can be monitored. These data can be used to elucidate transformation mechanisms (e.g.coherentversusincoherent growth), growth rates and orientation-dependent growth of individual grains. The methodology is demonstrated on the α–γ phase transitions in hydrous Mg2SiO4·H2O up to 22 GPa and 940 K. This transformation most likely occurs in the most abundant mineral of the Earth's upper mantle (Mg0.8Fe0.2SiO4) in deep cold subducted slabs and plays an important role in their subduction behaviour.
Determining the shape and periodicity of nanostructures using small-angle X-ray scattering
Authors: Sunday Daniel F. , List Scott , Chawla Jasmeet S. , Kline R. Joseph
Published: August 2015

The semiconductor industry is exploring new metrology techniques capable of meeting the future requirement to characterize three-dimensional structure where the critical dimensions are less than 10 nm. X-ray scattering techniques are one candidate owing to the sub-Å wavelengths which are sensitive to internal changes in electron density. Critical-dimension small-angle X-ray scattering (CDSAXS) has been shown to be capable of determining the average shape of a line grating. Here it is used to study a set of line gratings patternedviaa self-aligned multiple patterning process, which resulted in a set of mirrored lines, where the individual line shapes were asymmetric. The spacing between lines was systematically varied by sub-nm shifts. The model used to simulate the scattering was developed in stages of increasing complexity in order to justify the large number of parameters included. Comparisons between the models at different stages of development demonstrate that the measurement can determine differences in line shapes within the superlattice. The shape and spacing between lines within a given set were determined to sub-nm accuracy. This demonstrates the potential for CDSAXS as a high-resolution nanostructure metrology tool.
Single-crystal X-ray diffraction and resonant X-ray magnetic scattering at helium-3 temperatures in high magnetic fields at beamline P09 at PETRA III
Authors: Francoual S. , Strempfer J. , Warren J. , Liu Y. , Skaugen A. , Poli S. , Blume J. , Wolff-Fabris F. , Canfield P. C. , Lograsso T.
Published: August 2015

The resonant scattering and diffraction beamline P09 at PETRA III at DESY is equipped with a 14 T vertical field split-pair magnet. A helium-3 refrigerator is available that can be fitted inside the magnet's variable-temperature insert. Here the results of a series of experiments aimed at determining the beam conditions permitting operations with the He-3 insert are presented. By measuring the tetragonal-to-orthorhombic phase transition occurring at 2.1 K in the Jahn–Teller compound TmVO4, it is found that the photon flux at P09 must be attenuated down to 1.5 × 109 photons s−1for the sample to remain at temperatures below 800 mK. Despite such a reduction of the incident flux and the subsequent use of a Cu(111) analyzer, the resonant X-ray magnetic scattering signal at the TmLIIIabsorption edge associated with the spin-density wave in TmNi2B2C below 1.5 K is intense enough to permit a complete study in magnetic field and at sub-Kelvin temperatures to be carried out.
Principal time management skills
Authors: Grissom Jason A. , Loeb Susanna , Mitani Hajime
Published: August 2015

Purpose

– Time demands faced by school principals make principals’ work increasingly difficult. Research outside education suggests that effective time management skills may help principals meet job demands, reduce job stress, and improve their performance. The purpose of this paper is to investigate these hypotheses.

Design/methodology/approach

– The authors administered a time management inventory to nearly 300 principals in Miami-Dade County Public Schools, the fourth-largest school district in the USA. The authors analyzed scores on the inventory descriptively and used them to predict time-use data collected via in-person observations, a survey-based measure of job stress, and measures of perceived job effectiveness obtained from assistant principals and teachers in the school.

Findings

– Principals with better time management skills allocate more time in classrooms and to managing instruction in their schools but spend less time on interpersonal relationship-building. Perhaps as a result of this tradeoff, the authors find that associations between principal time management skills and subjective assessments of principal performance are mixed. The authors find strong evidence, however, that time management skills are associated with lower principal job stress.

Practical implications

– Findings suggest that building principals’ time management capacities may be a worthwhile strategy for increasing time on high-priority tasks and reducing stress.

Originality/value

– This study is the first to empirically examine time management among school principals and link time management to key principal outcomes using large-scale data.
The financing of small firms in Beijing, China: exploring the extent of credit constraints
Authors: Wang Jia , Robson Paul , Freel Mark
Published: August 2015

Purpose

– The purpose of this paper is to utilise a sample of 384 small and medium-sized enterprises (SMEs) who applied for external finance in the Beijing area of China to investigate the characteristics of firms against: the amount of external finance sought, the amount received, and the proportion of external finance which was received from the sought finance.

Design/methodology/approach

– The authors use a survey of SMEs in Beijing, China, undertaken between July and December 2007 where a response rate of 37.67 per cent was obtained. The survey was translated from English to Chinese, and then back translated from Chinese to English by academics with input from businesses. The sample of 384 firms is robust.

Findings

– Overall, there is little evidence in the sample of Chinese SMEs that innovative firms face discrimination from providers of credit. However, where innovation is measured by inputs (specifically R
&
D), providers of credit appear less comfortable. Three other factors were more important and were statistically significant at the 5 per cent level. For example, exporters were less likely to receive a greater proportion of their sought finance; and manufacturing firms were more likely than service sector firms, and limited liability companies were more likely than extended sole proprietorship firms to obtain a greater proportion of the external finance which they sought.

Research limitations/implications

– The sample for the research is from Beijing. Researchers may extent and role out the research to other parts of China.

Practical implications

– Practically, the authors explore variations in firm-level characteristics by: the amount of external finance sought, the amount of external finance received, and the ratio of “sought” to “received” external finance. In this way, the research questions are concerned with understanding which “types” of firms seek most bank finance, and which are most successful. This information is of benefit to SMEs, policy makers and those who work in the finance industry.

Social implications

– Access to finance is a cause of stress and anxiety to many SMEs. A greater understanding of the accessing of finance in Beijing China will allow entrepreneurs to be better placed to reflect upon their businesses and their suitability to pursue finance. This can help the economic and social well-being of entrepreneurs and their employees.

Originality/value

– There are comparatively few large scale surveys which have been undertaken of access to finance by SMEs in China, and within this field there is very little research which has been undertaken to look at innovators and non-innovators. The results allow us to have a better understanding of how much finance SMEs in Beijing are seeking, obtaining, and the proportion of finance received from that sought, and the extent to which innovation and other business and owner-manager characteristics are influential.
The influence of department policy and accountability on officer-involved collisions
Authors: Hansen J. Andrew , Rojek Jeff , Wolfe Scott E. , Alpert Geoffrey P.
Published: August 2015

Purpose

– Little is known regarding the impact of organizational policies and practices on police officers’ driving behaviors. To address an important gap in the empirical literature, this study examined how perceived likelihood of discipline for violations of agency driving policies impacted officer-involved vehicle collisions.

Design/methodology/approach

– Surveys were distributed to patrol officers and their supervisors in eight California law enforcement agencies. The surveys elicited information regarding the perceived likelihood of discipline for violations of agency driving policies regarding cell phone use, text messaging, seatbelt use, speeding, and vehicle operations during emergency and pursuit situations.

Findings

– The findings demonstrated a significant impact of perceived likelihood of enforcement for some but not all agency driving policies on officer-involved vehicle collisions.

Research limitations/implications

– This study was limited to self-reported data from patrol officers and their supervisors in eight California agencies.

Practical implications

– Findings suggest that agencies may reduce officer injuries and other costs by increasing supervision and enforcement of agency driving policies.

Originality/value

– This study contributes to the extant body of literature on officer-involved vehicle collisions by considering the impact of agency policy and supervision on officer behavior.
Sponsoring Private Member's Bills in Finland and Estonia: The Electoral Context of Legislative Behaviour
Authors: Solvak Mihkel , Pajala Antti
Published: August 2015

This article examines the degree to which sponsored private member's bills (PMBs) in parliament can be explained by electoral incentives. Such bills are a peculiar piece of draft legislation – technically simple, topically unimportant and with negligible passage rates. Yet members of parliament (MPs) sponsor them in large numbers. One possible explanation for this behaviour is the electoral context arising out of the variance in electoral district size and electoral list types, which makes a strong personal reputation comparatively more important for some MPs. Sponsoring bills that have no realistic chance of becoming actual regulations could be a form of personal reputation‐building and/or vote‐seeking behaviour. Evidence is examined on the sponsoring of such bills in Finland between 2003 and 2007 and in Estonia between 1999 and 2007 in order to determine if the electoral context explains why some MPs do this more frequently. The results suggest that the electoral system does have an effect. MPs who have been elected under rules where personal reputation is not central in getting elected are less likely to sponsor such bills the larger their electoral district becomes.
Effect of different matrices on probiotic resistance to in vitro simulated gastrointestinal conditions
Authors: Casarotti Sabrina N , Todorov Svetoslav D , Penna Ana Lúcia B
Published: August 2015

In this study, we evaluated the effect of different matrices (MRS, milk and milk with inulin) on the tolerance of probiotic strains (Lactobacillus acidophilus La‐5 and Bifidobacterium animalis subsp. lactis BB‐12) to simulated conditions similar to those found in the gastrointestinal tract. Both probiotic strains demonstrated a significantly lower viability after exposure to in vitro gastric and intestinal conditions, and B. animalis subsp. lactis BB‐12 showed higher survival during the test compared to L. acidophilus La‐5 in all tested matrices. Milk and inulin protected probiotics from in vitro gastrointestinal stress. These results suggest that it is critical to formulate the food matrix to be used as probiotic carrier.
Assessment of donkey milk chemical, microbiological and sensory attributes in Greece and Cyprus
Authors: Malissiova Eleni , Arsenos Georgios , Papademas Photis , Fletouris Dimitrios , Manouras Athanasios , Aspri Maria , Nikolopoulou Aikaterini , Giannopoulou Alexandra , Arvanitoyannis Ioannis S
Published: August 2015

This study aimed to assess the nutritional, hygienic and sensory characteristics of donkey milk produced in Greece and Cyprus. The average values for pH, fat, protein and lactose were 7.14, 0.52 g/100 mL, 1.22 g/100 mL and 7.01 g/100 mL, respectively, whereas aflatoxin M1 and beta‐lactam residues were not detected in any sample. The microbiological analysis revealed very low somatic cell counts and total microbial counts, while Escherichia coli, Salmonella spp and Listeria monocytogenes were not detected in any sample. The sensory evaluation classified the milk as white, thin, with a slightly sweet pleasant taste, pleasant milky aroma, sweet flavour and no persistent aftertaste.
Production of bacteriocin‐like inhibitory substances (BLIS) by Bifidobacterium lactis using whey as a substrate
Authors: Balciunas Eduardo Marcos , Al Arni Saleh , Converti Attilio , Leblanc Jean Guy , Oliveira Ricardo Pinheiro de Souza
Published: August 2015

The objective of this work was to evaluate the production of bacteriocin‐like inhibitory substances (BLIS) by Bifidobacterium animalis subsp. lactis in whey supplemented with yeast extract, inulin, Tween‐80 or l‐cysteine. Cell growth, acidification, glucose and lactose consumption as well as BLIS production were measured during fermentations carried out in shake flasks. The best additive for both cell growth and BLIS production was shown to be yeast extract, which gave the highest concentrations of biomass (9.9 log cfu/mL) and BLIS (800 AU/mL). In a bench‐scale fermentor, B. lactis growth and BLIS production were between 6% and 25% higher than in flasks depending on the conditions assayed.
Genotyping of the kappa‐casein and beta‐lactoglobulin genes in Anatolian water buffalo by PCR‐RFLP
Authors: Cinar Mehmet Ulas , Akyuz Bilal , Arslan Korhan , Ilgar Esma Gamze
Published: August 2015

The objective of this study was to identify allele and genotype frequencies of the κ‐CN and β‐LG genes in Anatolian water buffalo. A total of 126 water buffalos from Turkey were genotyped using the PCR‐RFLP method. For gene κ‐CN, only B allele and BB genotype were observed. And for gene β‐LG, two types of alleles (A and B) and three types of genotypes were observed. The genotype frequencies of AA, AB and BB of β‐LG in Anatolian water buffalo were 0.254, 0.698 and 0.048, respectively. Surprisingly, the frequency of allele A was higher than that of allele B in contrast to world buffalo breeds.
Scavenger Species‐typical Alteration to Bone: Using Bite Mark Dimensions to Identify Scavengers
Authors: Young Alexandria , Stillman Richard , Smith Martin J. , Korstjens Amanda H.
Published: August 2015

Scavenger‐induced alteration to bone occurs while scavengers access soft tissue and during the scattering and re‐scavenging of skeletal remains. Using bite mark, dimensional data to assist in the more accurate identification of a scavenger can improve interpretations of trauma and enhance search and recovery methods. This study analyzed bite marks produced on both dry and fresh surface deposited remains by wild and captive red fox (Vulpes vulpes) and Eurasian badger (Meles meles), as well as domestic dog (Canis familiaris). The bite marks produced by foxes were distinguishable from those made by badgers and dogs based on ranges of mean length and breadth of pits. The dimensional data of bite marks produced by badgers and dogs were less discernible. Bone modifications vary due to a variety of factors which must be considered, such as scavenger species‐typical scavenging behavior, scavenger species' dentition, condition and deposition of remains, and environmental factors.
Describing Quality and Sensory Attributes of 3 Mango (Mangifera indica L.) Cultivars at 3 Ripeness Stages Based on Firmness
Authors: Nassur Rita de Cássia Mirela Resende , González‐Moscoso Sara , Crisosto Gayle M. , Lima Luiz Carlos de Oliveira , Vilas Boas Eduardo Valério de Barros , Crisosto Carlos H.
Published: August 2015

To determine the ideal ripening stage for consumption of the mango cultivars, “Ataulfo,” “Haden,” and “Tommy Atkins”; fruits at 3 flesh firmness levels (ripeness stages) were evaluated by a trained panel using descriptive analysis after instrumental measurements were made. After harvest, all fruits were ripened to allow softening and quality and sensory attribute changes. Ripening changes during softening of Ataulfo mangos were expressed by a characteristic increase in the perception of “tropical fruit” and “peach” aromas, an increase in “juiciness,” “sweetness,” and “tropical fruit” flavor, while “fibrousness,” “chewiness,” and “sourness” decreased. Similar desirable sensory changes were also detected during softening of Haden mangos; an increase in tropical fruit and peach aromas, sweetness and tropical fruit flavor, and a decrease in chewiness, sourness, and bitterness. Softening of Tommy Atkins mangos was followed by reduced chewiness and sourness and increased peach aroma. Softening of all cultivars was followed by decreased sourness and titratable acidity (TA) and increased soluble solids concentration (SSC) and SSC:TA ratio. The results indicate that mango ripening leads to increased expression of sensory attributes such as tropical fruit and peach aromas, tropical flavor, and sweetness that have been related to improved eating quality and these final changes in sensory quality attributes are specific for each cultivar. For example, Ataulfo and Haden mangos had greater improvement in quality and sensory attributes related to fruit eating quality during ripening‐softening than Tommy Atkins. In our consumer test, these quality‐sensory attributes expressed during ripening that were perceived by the trained panel were also validated, supporting the need for a controlled ripening protocol in mangos.
Symptom characteristics of depressive episodes prior to the onset of mania or hypomania
Authors: Pfennig A. , Ritter P. S. , Höfler M. , Lieb R. , Bauer M. , Wittchen H.‐U. , Beesdo‐Baum K.
Published: August 2015

Objective

Depressive episodes are typically the initial presentation of bipolar disorder. The evidence as to whether depressive episodes occurring in persons who later convert to bipolar disorder are symptomatically distinct from episodes of unipolar depression remains controversial. As there are crucial differences in the therapeutic management, symptom profiles indicating subsequent bipolar conversion may aid in appropriate treatment.

Method

A representative community sample of originally N = 3021 adolescents and young adults aged 14–24 years at baseline was assessed up to four times over 10 years. Assessment of symptoms was conducted by clinically trained interviewers using the standardized M‐CIDI. Symptom profiles of depressive episodes were compared via logistic regression between subjects that subsequently developed (hypo‐)manic episodes (n = 35) or remained unipolar depressive (n = 659).

Results

Initial depression amongst prospective converters was characterized by significantly increased suicidality (odds ratio, OR = 2.31), higher rates of feelings of worthlessness and excessive guilt (OR = 2.52), complete loss of pleasure (OR = 2.53) and diurnal variation (OR = 4.30). No differences were found for hyperphagia, hypersomnia and psychomotor alterations.

Conclusion

Findings suggest that the symptom profile of initial depressive episodes may be useful in the identification of subjects with an elevated risk for the subsequent conversion to bipolar disorder.
Decreased fertility rates in 9639 women diagnosed with inflammatory bowel disease: a United Kingdom population‐based cohort study
Authors: Ban L. , Tata L. J. , Humes D. J. , Fiaschi L. , Card T.
Published: August 2015

Background

Clinical studies have reported reduced fertility in women with inflammatory bowel disease (IBD).

Aim

To compare fertility rates in women with IBD to those in women without IBD and assess whether the relative fertility differed following IBD diagnosis, flares and surgery.

Methods

Women aged 15–44 years in 1990–2010 were identified from a UK primary care database. We estimated overall and age‐specific fertility rates by 5‐year age bands for women with and without IBD. We used Poisson regression to calculate adjusted fertility rate ratios (AFRR), adjusted for age, smoking and socioeconomic deprivation.

Results

There were 46.2 live births per 1000 person‐years [95% confidence interval (95% CI); 44.6–47.9] in 9639 women with IBD and 49.3 (95% CI 49.2–49.5) in 2 131 864 without (AFRR: 0.93; 95% CI: 0.89–0.96). Excluding periods of contraception use, the AFRR was 0.99 (95% CI: 0.95–1.03). Before diagnosis, the AFRR for women with ulcerative colitis (UC) was 1.07 (95% CI: 0.99–1.16) and was 0.88 (95% CI: 0.81–0.97) for women with CD. After diagnosis, AFRRs were 0.87 (95% CI: 0.82–0.94) for CD and 0.92 (95% CI: 0.86–1.00) for UC. The fertility rate was lower following flares (AFRR: 0.70; 95% CI: 0.59–0.82) or surgery (AFRR: 0.84; 95% CI: 0.77–0.92). Women with pouch and non‐pouch surgery had similar overall fertility though the reduction after surgery was greater for pouches (AFRR: 0.48; 95% CI: 0.23–0.99).

Conclusions

Women with Crohn's disease have marginally lower fertility rates. These rates decreased following flares and surgical interventions. Fertility rates returned almost to normal when women were not prescribed contraception but the reduction following surgical intervention remained. As the lifetime effect of pouch vs. nonpouch surgery on fertility is small, the reduction post‐pouch surgery should be interpreted with caution.
Flumazenil, naloxone and the ‘coma cocktail’
Authors: Sivilotti Marco L.A.
Published: August 2015

Flumazenil and naloxone are considered to be pharmacologically ideal antidotes. By competitive binding at the molecular target receptors, they are highly specific antagonists of two important drug classes, the benzodiazepines and opioids, respectively. Both antidotes enjoy rapid onset and short duration after parenteral administration, are easily titrated and are essentially devoid of agonist effects. Yet only naloxone is widely used as a component of the ‘coma cocktail’, a sequence of empirical treatments to correct altered mental status, while experts discourage the use of flumazenil for such patients. This review contrasts the history, indications, published evidence and novel applications for each antidote in order to explain this disparity in the clinical use of these ‘ideal’ antidotes.
Fatigue in chronic hepatitis C infection: Understanding patients' experience from a cognitive‐behavioural perspective
Authors: Zalai Dora , Carney Colleen E. , Sherman Morris , Shapiro Colin M. , McShane Kelly
Published: August 2015

Objectives

Fatigue is a leading concern of patients with chronic hepatitis C virus (HCV) infection. Despite its clinical significance, fatigue in HCV is poorly understood and therefore invariably under‐treated. A cognitive‐behavioural approach offers a framework to understand and treat fatigue, but the characteristics of fatigue in chronic HCV infection have not been documented from a cognitive‐behavioural perspective. This study captured the common and unique aspects of fatigue from a cognitive‐behavioural perspective in individuals with HCV infection and clinically significant fatigue.

Design

Cross‐sectional, qualitative using a critical realism approach.

Methods

Fourteen individuals (64% women; age >18 years) participated in semi‐structured interviews. The interviews documented the features, course, and perceived antecedents of fatigue; fatigue‐specific cognitions; fatigue management behaviours; and the functional impact of fatigue.

Results

Participants' descriptions included the aspects of fatigue that have been targets of cognitive‐behavioural therapy in other medical conditions, including attributing fatigue to the illness; expectation of chronicity; low control; and fatigue‐driven coping. There were also components of fatigue experience that appear to be unique characteristics of fatigue related to HCV, including predominantly physical fatigue; high acceptance of fatigue; and liver‐protective diet as a fatigue management behaviour.

Conclusions

This was the first study to document the experience of fatigue in chronic HCV infection in a cognitive‐behavioural framework. The findings suggest that the cognitive‐behavioural approach can be applied to fatigue in chronic HCV infection. This would open an avenue to alleviate fatigue and thus improve the primary patient‐reported outcome of the disease.

Statement of contribution

What is already known on this subject?

Fatigue is a key patient‐reported outcome measure of chronic hepatitis C virus (HCV) infection.

Fatigue management is not part of the standard care, because fatigue is poorly characterized in this population.

What does this study add?

A cognitive‐behavioural approach can be applied to understand fatigue in HCV infection.

Identified aspects of fatigue (antecedents, consequences, cognitions, behaviours) that can be treatment targets.

Cognitive‐behavioural therapy would open a new treatment avenue to alleviate fatigue in HCV infection.
Airway responsiveness to mannitol in asthma is associated with chymase‐positive mast cells and eosinophilic airway inflammation
Authors: Sverrild A. , Bergqvist A. , Baines K. J. , Porsbjerg C. , Andersson C. K. , Thomsen S. F. , Hoffmann H. J. , Gibson P. , Erjefält J. S. , Backer V.
Published: August 2015

Background

Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell‐associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol.

Methods

Airway hyperresponsiveness to inhaled mannitol was measured in 23 non‐smoking, corticosteroid‐free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell‐associated genes was measured by real‐time PCR.

Results

The proportion of submucosal MCTC was higher in asthmatic individuals with AHR to mannitol compared with asthmatic individuals without AHR (median: 40.3% vs. 18.7%, P = 0.03). Increased submucosal MCTC numbers were associated with increased levels of mRNA for thymic stromal lymphopoietin (TSLP) and CPA3 in asthmatics. Reactivity to mannitol correlated significantly with eosinophils in submucosa (r(s): 0.56, P = 0.01).

Conclusion

Airway hyperresponsiveness to inhaled mannitol is associated with an altered submucosal mast cell profile in asthmatic individuals. This mast cell profile is associated with increased levels of TSLP and CPA3. The degree of AHR to mannitol is correlated with the degree of eosinophilic inflammation in the airway submucosa.
Treatment options in the young patient with Graves' disease
Authors: Cheetham Tim , Bliss Richard
Published: August 2015

The treatment options in the young patient with Graves' disease are the same as in adults, namely antithyroid drug (ATD), surgery (partial or total thyroidectomy) and radioiodine. However, the emphasis and expectation is different in the young person, reflecting a range of considerations including age, pubertal status, disease natural history, likely impact of ATD on disease course and the implications of radiation exposure. New therapeutic strategies that could increase the likelihood of long‐term remission are being explored.
Adequacy of published screening criteria for retinopathy of prematurity
Authors: Taranath Deepa A , Oh Dickson D‐S , Keane Miriam C , Fabel Helen , Marshall Peter
Published: August 2015

Background

Criteria for screening preterm infants for retinopathy of prematurity vary around the world. We aimed to analyse the efficacy of alternative screening criteria.

Design

We collected retrospective data at a tertiary level neonatal nursery.

Participants

Our participants were 1007 babies, born between 1997 and 2011, at <32 weeks gestational age or <1500 g birth weight (as recommended by the National Health and Medical Research Council in 1996), who had completed follow‐up to full retinal vascularization, with defined presence or absence of retinopathy of prematurity.

Methods

We determined whether disease would be detected using an alternative Australian screening model (gestational age <30 weeks or birth weight <1250 g) or screening criteria utilized in developed countries with similar standards of neonatal care.

Main Outcome Measures

Detection of retinopathy of prematurity is our main outcome.

Results

Using several of the alternative criteria, two neonates with clinically significant retinopathy of prematurity, one of whom required laser treatment to preserve sight, would not have been screened, and their disease may have gone undetected. Use of <30 weeks gestational age or <1500 g birth weight as the criteria would still have screened these infants but would have reduced the number of infants screened by 24.9%.

Conclusions

Some commonly utilized international screening criteria for retinopathy of prematurity may risk clinically significant cases being missed and others may screen babies unnecessarily. Alternative criteria should be considered and ‘<30 weeks gestational age and/or <1500 g birth weight’ appears a viable option.
Bone Ceramic® at Implants Installed Immediately into Extraction Sockets in the Molar Region: An Experimental Study in Dogs
Authors: Pereira Flávia Priscila , Hochuli‐Vieira Eduardo , Maté Sánchez de Val José E. , De Santis Enzo , Salata Luiz Antonio , Botticelli Daniele
Published: August 2015

Purpose

The aim of this paper was to study the healing of 1–1.4 mm wide buccal defects at implants placed immediately into extraction sockets (IPIES) filled with a mixture of synthetic hydroxyapatite (HA) 60% and beta‐tricalciumphosphate (TCP) 40% or left with the clot alone and both covered with collagen membranes.

Material and Methods

Eight Labrador dogs were used and implants were placed immediately into the extraction sockets of the first molar bilaterally. A mixture of synthetic HA 60% and beta‐TCP 40% at the test or the clot alone at the control sites were used to fill the defects. All surgical sites were subsequently covered by a resorbable collagen membrane and a non‐submerged healing was allowed. After 4 months, the animals were euthanized, biopsies harvested and processed for histomorphometric analysis.

Results

At the time of installation, residual buccal defects occurred that were 1.1 mm and 1.4 mm wide and 3 mm and 4 mm deep at the control and test sites, respectively. After 4 months of healing, the top of the bony crest and the coronal level of osseointegration were located respectively at 0.1 ± 1.8 mm and 1.5 ± 1.8 mm at the test, and 0.6 ± 1.6 mm and 1.2 ± 0.7 mm at the control sites apically to the implant shoulder. Bone‐to‐implant contact at the buccal aspect was 34.9 ± 25.9% and 36.4 ± 17.3% at the test and control sites, respectively. No statistically significant differences were found between test and control sites for any of the variables analyzed at the buccal aspects.

Conclusions

The use of a mixture of synthetic HA 60% and beta‐TCP 40% to fill residual buccal defects 1–1.4 mm wide at IPIES did not improve significantly the results of healing.
Cardiovascular and heart failure safety profile of vildagliptin: a meta‐analysis of 17 000 patients
Authors: McInnes G. , Evans M. , Del Prato S. , Stumvoll M. , Schweizer A. , Lukashevich V. , Shao Q. , Kothny W.
Published: August 2015

Aims

To report the cardiovascular (CV) safety profile and heart failure (HF) risk of vildagliptin from a large pool of studies, including trials in high‐risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment.

Methods

We conducted a retrospective meta‐analysis of prospectively adjudicated CV events. Patient‐level data were pooled from 40 double‐blind, randomized controlled phase III and IV vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of vildagliptin (50 mg once‐ and twice‐daily combined) versus comparators (placebo and all non‐vildagliptin treatments) was calculated using the Mantel–Haenszel (M–H) method.

Results

Of the 17 446 patients, 9599 received vildagliptin (9251.4 subject‐years of exposure) and 7847 received comparators (7317.0 subject‐years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m2 (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) vildagliptin‐treated patients and 85 (1.20%) comparator‐treated patients, with an M‐H RR of 0.82 [95% confidence interval (CI) 0.61–1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) vildagliptin‐treated patients and 32 (0.45%) comparator‐treated patients, with an M–H RR 1.08 (95% CI 0.68–1.70).

Conclusions

This large meta‐analysis indicates that vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in vildagliptin‐treated patients.
Body shape variation in two species of darters (Etheostoma, Percidae) and its relation to the environment
Authors: Hopper Garrett W. , Morehouse Reid L. , Tobler Michael
Published: August 2015

Environmental variation can shape phenotypic variation in organisms, but most evidence for trait differentiation comes from analyses of dichotomous habitat types that differ in only one or few key environmental factors. In reality, environmental variation is often more subtle, gradual and multifarious. Here, we investigated geographic variation in body shape of two darter species (Etheostoma spectabileandEtheostoma flabellare; Percidae) that occur along river gradients. This study addressed three specific questions: Is there intraspecific geographic variation in the two species across different sites in the Ozark Highlands of Oklahoma (USA)? Is phenotypic variation across sites correlated with abiotic environmental conditions? Do the two species share site‐specific (i.e. convergent) phenotypic variation in areas where they occur together? Our results indicated significant body shape variation in both species. Population differences in body shape were particularly correlated with variation in substrate composition. The combined analysis of both species indicated a small but significant effect of convergence on body shape wherever they are sympatric; shared variation, however, was not related to any environmental variables included in the analysis. While it remains unclear whether phenotypic variation in these species is due to heritable differentiation or environmentally induced plasticity, our results indicate that even subtle and gradual environmental variation can induce substantial variation in phenotypes on a relatively small spatial scale.
White matter alterations in patients with MRI‐negative temporal lobe epilepsy and their asymptomatic siblings
Authors: Whelan Christopher D. , Alhusaini Saud , O'Hanlon Erik , Cheung Maria , Iyer Parames M. , Meaney James F. , Fagan Andrew J. , Boyle Gerard , Delanty Norman , Doherty Colin P. , Cavalleri Gianpiero L.
Published: August 2015

Objective

The identification of “endophenotypes”—measurable variations along the pathways between genes and distal disease state—may help deconstruct focal epilepsies into more sensitive phenomena and improve future efforts to map the genetic underpinnings of the disorder. In this study, we set out to determine if diffusion tensor imaging (DTI)–inferred white matter (WM) alterations represent a suitable structural endophenotype for focal epilepsy.

Methods

We recruited 25 patients with sporadic mesial temporal lobe epilepsy (MTLE) with normal magnetic resonance imaging (MRI) findings, 25 of their gender‐matched, asymptomatic siblings, and 60 control subjects. Whole‐brain, voxelwise statistics were conducted to identify regions of microstructural degeneration in patients with MTLE and/or their asymptomatic siblings. WM tracts exhibiting evidence of microstructural disruption were then reconstructed using deterministic tractography. Diffusion metrics including fractional anisotropy (FA) and mean diffusivity (MD) were compared across groups using a series of one‐way multivariate analyses of covariance (MANCOVAs).

Results

Voxelwise statistics revealed significant FA reductions in the corpus callosum (CC), bilateral superior longitudinal fasciculi (SLF), bilateral inferior longitudinal fasciculi (ILF), and left corticospinal tract (CST) in MTLE patients only. MD increases were observed in MTLE patients and their asymptomatic siblings in the left SLF and left CST. Deterministic tractography supported the voxelwise results, revealing significant FA alterations in the left SLF and CST in patients only and significant MD alterations in MTLE patients and their unaffected siblings. The diffusion scalars of MTLE patients and their asymptomatic siblings were highly correlated in the SLF and CST ipsilateral to patients' sides of seizure onset.

Significance

These findings confirm the presence of microstructural WM alterations in patients with MRI‐negative MTLE and provide preliminary support for a diffusion‐based endophenotype in the disorder. Further studies of narrow‐sense heritability in larger cohorts of first‐degree relatives of MTLE patients are required to confirm these results.
Beyond the Binary: Trans‐Negotiations in Couple and Family Therapy
Authors: Giammattei Shawn V.
Published: August 2015

Dualistic notions about gender and sexuality have permeated the field of couple and family therapy. These binary constructions have been limiting for everyone, especially those who fall outside the male/female dichotomy. This article examines the impact of these binary notions, especially on transgender and gender‐creative individuals, couples, and families. Current theory and research in the field as they relate to gender identity, sexuality, and gender minority stress in couples and families are presented. Case examples are used to illustrate affirmative approaches to treatment issues such as coming out, safety, grief and loss, redefining relationships, and social/medical transitions that may arise for transgender or gender nonconforming (TGNC) individuals, couples, and families.
Structural insights on complement activation
Authors: Alcorlo Martín , López‐Perrote Andrés , Delgado Sandra , Yébenes Hugo , Subías Marta , Rodríguez‐Gallego César , Rodríguez de Córdoba Santiago , Llorca Oscar
Published: August 2015

The proteolytic cleavage of C3 to generate C3b is the central and most important step in the activation of complement, a major component of innate immunity. The comparison of the crystal structures of C3 and C3b illustrates large conformational changes during the transition from C3 to C3b. Exposure of a reactive thio‐ester group allows C3b to bind covalently to surfaces such as pathogens or apoptotic cellular debris. The displacement of the thio‐ester‐containing domain (TED) exposes hidden surfaces that mediate the interaction with complement factor B to assemble the C3‐convertase of the alternative pathway (AP). In addition, the displacement of the TED and its interaction with the macroglobulin 1 (MG1) domain generates an extended surface in C3b where the complement regulators factor H (FH), decay accelerating factor (DAF), membrane cofactor protein (MCP) and complement receptor 1 (CR1) can bind, mediating accelerated decay of the AP C3‐convertase and proteolytic inactivation of C3b. In the last few years, evidence has accumulated revealing that the structure of C3b in solution is significantly more flexible than anticipated. We review our current knowledge on C3b structural flexibility to propose a general model where the TED can display a collection of conformations around the MG ring, as well as a few specialized positions where the TED is held in one of several fixed locations. Importantly, this conformational heterogeneity in C3b impacts complement regulation by affecting the interaction with regulators.
A spatial assessment of potential biomass for bioenergy in Australia in 2010, and possible expansion by 2030 and 2050
Authors: Crawford Debbie F. , O'Connor Michael H. , Jovanovic Tom , Herr Alexander , Raison Robert John , O'Connell Deborah A. , Baynes Tim
Published: August 2015

This paper provides spatial estimates of potentially available biomass for bioenergy in Australia in 2010, 2030 and 2050 (under clearly stated assumptions) for the following biomass sources: crop stubble, native grasses, pulpwood and residues (created either during forest harvesting or wood processing) from plantations and native forests, bagasse, organic municipal solid waste and new short‐rotation tree crops. For each biomass type, we estimated annual potential availability at the finest scale possible with readily accessible data, and then aggregated to make estimates for each of 60 Statistical Divisions (administrative areas) across Australia. The potentially available lignocellulosic biomass is estimated at approximately 80 Mt per year, with the major contributors of crop stubble (27.7 Mt per year), grasses (19.7 Mt per year) and forest plantations (10.9 Mt per year). Over the next 20–40 years, total potentially available biomass could increase to 100–115 Mt per year, with new plantings of short‐rotation trees being the major source of the increase (14.7 Mt per year by 2030 and 29.3 Mt per year by 2050). We exclude oilseeds, algae and ‘regrowth’, that is woody vegetation naturally regenerating on previously cleared land, which may be important in several regions of Australia (Australian Forestry 77, 2014, 1; Global Change Biology Bioenergy 7, 2015, 497). We briefly discuss some of the challenges to providing a reliable and sustainable supply of the large amounts of biomass required to build a bioenergy industry of significant scale. More detailed regional analyses, including of the costs of delivered biomass, logistics and economics of harvest, transport and storage, competing markets for biomass and a full assessment of the sustainability of production are needed to underpin investment in specific conversion facilities (e.g. Opportunities for forest bioenergy: An assessment of the environmental and economic opportunities and constraints associated with bioenergy production from biomass resources in two prospective regions of Australia, 2011a).