bluuebunny/crossref_metadata_2025_split huggingface dataset:
An adaptive design to investigate the effect of ketoconazole on pharmacokinetics of GSK239512 in healthy male volunteers
Authors: Xu Jianfeng , Hilpert Jan , Wu Kai , van Hecke Benjamin , Collins Gary , Patel Aarti , Mohindra Rajat , Davies Matt J. B. , Xu Yanmei , Thompson Paul 
Published: December 2014

AbstractThis open label drug‐drug interaction (DDI) study investigated the effect of a strong CYP3A inhibitor ketoconazole on the PK and safety profile of GSK239512. To mitigate the tolerability concerns of high GSK239512 exposures resulting from CYP3A inhibition, a 2‐cohort adaptive design was used to facilitate a stepwise selection of dose levels and subject numbers. In Cohort 1, 6 subjects received a single dose of 20 μg GSK239512 alone and then 10 μg GSK239512 in combination with repeated once daily doses of 400 mg ketoconazole. The results from Cohort 1 demonstrated an approximately 1.5‐fold increase in GSK239512 exposure with a good tolerability profile. This led to the adoption of a 3‐session option in Cohort 2, in which 16 subjects received sequential single doses of 20 μg GSK239512 alone, 40 μg GSK239512 alone, and a single dose of 40 μg GSK239512 in combination with repeated once daily doses of 400 mg ketoconazole. The 2‐cohort adaptive design proved effective in mitigating any potentially significant DDI risk to healthy subjects. Final results showed a 1.3‐fold increase in GSK239512 exposure with ketoconazole, suggesting that in vivo metabolism of GSK239512 by CYP3A is unlikely to be the primary route of GSK239512 elimination.
Fibrous dysplasia of the temporal bone: A review of 66 cases
Authors: Frisch Christopher D. , Carlson Matthew L. , Kahue Charissa N. , Pelosi Stanley , Haynes David S. , Lane John I. , Neff Brian A. , Link Michael J. , Driscoll Colin L. W. 
Published: December 2014

Objectives/HypothesisFibrous dysplasia is a condition of nonmalignant osseous change and may occur in a monostotic or polyostotic pattern, the latter potentially being associated with McCune‐Albright syndrome. Symptoms are highly variable and dependent upon lesion location and size.Study DesignRetrospective review.MethodsConsecutive subjects with fibrous dysplasia of the temporal bone were evaluated between 2000 and 2013 at two tertiary academic referral centers. Main outcome measures included disease presentation, diagnostic evaluation, management strategy, and outcome.ResultsSixty‐six patients with fibrous dysplasia of the skull were found to have involvement of the temporal bone. The mean age at diagnosis was 25 years, 39 (59%) were female, and the mean duration of follow‐up was 48 months. Six (11%) patients had monostotic disease, with the remaining 60 (89%) patients having the polyostotic form; 16 (24%) patients had McCune‐Albright syndrome. The most common presenting complaint was headache (59%), followed by hearing loss (29%). The most common exam finding was cosmetic deformity (50%). Cholesteatoma (3%) and spontaneous cerebrospinal fluid fistula (1.5%) were found in a small percentage. No patients had evidence of motor cranial neuropathy by history or physical examination.ConclusionsThe clinical presentation of fibrous dysplasia involving the temporal bone is variable. A growing number of patients are diagnosed incidentally through imaging, and since most patients experience a benign course, the majority can be followed clinically without need for intervention.Level of Evidence4. Laryngoscope, 125:1438–1443, 2015
Kinetic Study on the Catalytic Effect of Ionic Liquids on the Polymerization of Methyl Methacrylate Co‐initiated by Imine Bases
Authors: Polenz Ingmar , Tchernook Ivan , Friedrich Joachim , Schmidt Friedrich Georg , Spange Stefan 
Published: December 2014

The polymerization of methyl methacrylate (MMA) co‐initiated by imine bases (IBA) is significantly accelerated by ionic liquids (ILs). IL traces added to an imine base/MMA mixture lead to both a significant decrease of the IBA polymerization activation temperature (as well as the Arrhenius activation energy) and an increase of the polymerization rate. The radical character of the polymerization is proved by copolymerization experiments of MMA with methacrylonitrile and comparison with literature known copolymerization parameters. The polymerization kinetics and temperature dependence of this process in the presence of the IL are quantified by the polymerization rate law, revealing the tremendous impact of the IL on the monomer consumption. The mechanistic interpretations are supported by DFT calculations. The activation of the IBA polymerization is strongly dependent on the IL interaction strengths with the IBA components, as suggested by correlation of kP with the empirically determined Kamlet–Taft parameters α and β of the IL. Complex interaction events are responsible for the acceleration.
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Variability in pathogenicity prediction programs: impact on clinical diagnostics
Authors: Walters‐Sen Lauren C. , Hashimoto Sayaka , Thrush Devon Lamb , Reshmi Shalini , Gastier‐Foster Julie M. , Astbury Caroline , Pyatt Robert E. 
Published: December 2014

AbstractCurrent practice by clinical diagnostic laboratories is to utilize online prediction programs to help determine the significance of novel variants in a given gene sequence. However, these programs vary widely in their methods and ability to correctly predict the pathogenicity of a given sequence change. The performance of 17 publicly available pathogenicity prediction programs was assayed using a dataset consisting of 122 credibly pathogenic and benign variants in genes associated with the RASopathy family of disorders and limb‐girdle muscular dystrophy. Performance metrics were compared between the programs to determine the most accurate program for loss‐of‐function and gain‐of‐function mechanisms. No one program correctly predicted the pathogenicity of all variants analyzed. A major hindrance to the analysis was the lack of output from a significant portion of the programs. The best performer was MutPred, which had a weighted accuracy of 82.6% in the full dataset. Surprisingly, combining the results of the top three programs did not increase the ability to predict pathogenicity over the top performer alone. As the increasing number of sequence changes in larger datasets will require interpretation, the current study demonstrates that extreme caution must be taken when reporting pathogenicity based on statistical online protein prediction programs in the absence of functional studies.
Mikrobielle Artenvielfalt unter dem Eis der Antarktis
Authors: Groß Michael 
Published: December 2014

AbstractDie Oberfläche des kalten Kontinents gilt offiziell als Wüste. Doch in den zahllosen Gewässern, die sich unter dem Eis verbergen, gibt es Ökosysteme, die von der Chemosynthese leben.
Surface nitridation for improved dielectric/III‐nitride interfaces in GaN MIS‐HEMTs
Authors: Chen Kevin J. , Yang Shu , Tang Zhikai , Huang Sen , Lu Yunyou , Jiang Qimeng , Liu Shenghou , Liu Cheng , Li Baikui 
Published: December 2014

AbstractEffective interface engineering techniques in III‐nitride heterojunction power devices, aiming at yielding high VTH stability in insulated‐gate devices and suppressed current collapse in high‐voltage switching operation, are of critical significance to enhance device performance and reliability. In this work, we present an interface enhancement technology featuring in situ low‐damage NH3/Ar/N2 pre‐gate plasma treatment prior to the ALD‐Al2O3 deposition for high‐performance III‐nitride MIS‐HEMTs. It is manifest that this technology can effectively remove the native oxide while forming a monocrystal‐like nitridation interfacial‐layer (NIL) on the III‐nitride surface. The Al2O3(NIL)/GaN/AlGaN/GaN MIS‐heterostructures with high‐quality interface exhibit well‐behaved electrical characteristics, including a small subthreshold swing of ∼64 mV/dec, a small hysteresis of ∼0.09 V, tiny f/T dispersions in the C–V characteristics, and low interface trap density of ∼1 × 1012–6 × 1012 cm−2eV−1. Cross‐sectional TEM micrograph of the Al2O3/III‐nitride gate stack with a monocrystal‐like nitridation interfacial‐layer (NIL).
(In)formality: the meshwork of water service provisioning
Authors: Schwartz Klaas , Tutusaus Luque Mireia , Rusca Maria , Ahlers Rhodante 
Published: December 2014

Cities in developing countries have for many decades been characterized by the co‐existence of different service provision modalities. These modalities usually include a formal water utility and an array of small‐scale private or community‐based service providers. In recent years, the topic of informality in water provisioning has been subject to an upsurge in interest of both policy makers and academics. Frequently, literature on the topic distinguishes between informal providers and formal providers suggesting that a provider belongs to either a formal or informal domain. By highlighting the infrastructure, financing, and regulatory institutions of small‐scale service provisioning in Greater Maputo, Mozambique, this article illustrates how informality and formality are interdependent and permeate throughout the water provisioning process creating a meshwork of service provisioning. Actors involved in service provisioning embody multiple identities and use these identities in various sites of governance in order to develop their water business. By adopting this approach to informality, it becomes impossible to distinguish convincingly between formal and informal providers. Instead, it leads to a focus on water provisioning rather than providers, in which informality and formality traverse through the service provision process. WIREs Water 2015, 2:31–36. doi: 10.1002/wat2.1056This article is categorized under:

Engineering Water > Planning Water
Human Water > Water Governance
Transboundary hydro‐politics and climate change rhetoric: an emerging hydro‐security complex in the lake chad basin
Authors: Asah Stanley T. 
Published: December 2014

The likelihood of conflict and consequent need for cooperation are soaring with increasing pressures on scarce and often exploited water resources in shared hydrologic units. Questions of equitable water allocation and distributions of social‐ecological costs and benefits—who gets what, how much, and why—are important for fostering cooperation and managing conflict in transboundary water management. Hydropolitics is an analytic tool for understanding how power shapes water claims and uses in transboundary hydrologic units. Through the lens of hydropolitics, I show how various forms of power explain water claims and uses by riparian nations within the Lake Chad Basin (LCB). I explain how rhetoric, including the rhetoric of climate change, mask local human‐driven causes of social‐ecological degradation, thereby misappropriating agency and responsibility for sustainable water management within the LCB. I show that water is a security issue within the basin and closely related to other regional security issues, and argue that the inter‐linkages of security issues, together with the differential evolution of state capabilities, may facilitate the emergence of a hydro‐security complex within the basin. A more nuanced understanding of hydropolitics, including rhetoric and hydrosecurity, is necessary for sustainable transbounadry water management and water use security. WIREs Water 2015, 2:37–45. doi: 10.1002/wat2.1057This article is categorized under:

Human Water > Rights to Water
Science of Water > Water and Environmental Change
Human Water > Water Governance
Advances in synapse formation: forging connections in the worm
Authors: Cherra Salvatore J. , Jin Yishi 
Published: December 2014

AbstractSynapse formation is the quintessential process by which neurons form specific connections with their targets to enable the development of functional circuits. Over the past few decades, intense research efforts have identified thousands of proteins that localize to the pre‐ and postsynaptic compartments. Genetic dissection has provided important insights into the nexus of the molecular and cellular network, and has greatly advanced our knowledge about how synapses form and function physiologically. Moreover, recent studies have highlighted the complex regulation of synapse formation with the identification of novel mechanisms involving cell interactions from non‐neuronal sources. In this review, we cover the conserved pathways required for synaptogenesis and place specific focus on new themes of synapse modulation arising from studies in Caenorhabditis elegans. WIREs Dev Biol 2015, 4:85–97. doi: 10.1002/wdev.165This article is categorized under:

Gene Expression and Transcriptional Hierarchies > Cellular Differentiation
Signaling Pathways > Cell Fate Signaling
Nervous System Development > Worms
Biocatalytic deracemisation of aliphatic β-hydroxy esters: Improving the enantioselectivity by optimisation of reaction parameters
Authors: Venkataraman Sowmyalakshmi , Chadha Anju 
Published: December 2014

Abstract
Optically pure aliphatic β-hydroxy esters were prepared from their racemates by deracemisation using the biocatalyst Candida parapsilosis ATCC 7330. High optical purity (up to &gt;99 %) and good yields (up to 71 %) of the product secondary alcohols were obtained. This study highlights the importance of optimization of reaction conditions using ethyl-3-hydroxybutanoate as the model substrate to improve the enantioselectivity (enantiomeric excess from 9 to 98 %). The present study emphasises the broad substrate scope of the biocatalyst towards deracemisation. This is the first report of Candida parapsilosis ATCC 7330-mediated deracemisation of various alkyl-3-hydroxybutanoates to produce either the (R)-enantiomers (methyl, ethyl, propyl, butyl, t-butyl, allyl-3-hydroxybutanoates) or (S)-enantiomers (pentyl, iso-amyl and iso-propyl-3-hydroxybutanoates).
Public Health Genetic Counselors: Activities, Skills, and Sources of Learning
Authors: McWalter Kirsty M. , Sdano Mallory R. , Dave Gaurav , Powell Karen P. , Callanan Nancy 
Published: December 2014

AbstractSpecialization within genetic counseling is apparent, with 29 primary specialties listed in the National Society of Genetic Counselors’ 2012 Professional Status Survey (PSS). PSS results show a steady proportion of genetic counselors primarily involved in public health, yet do not identify all those performing public health activities. Little is known about the skills needed to perform activities outside of “traditional” genetic counselor roles and the expertise needed to execute those skills. This study aimed to identify genetic counselors engaging in public health activities, the skills used, and the most influential sources of learning for those skills. Participants (N = 155) reported involvement in several public health categories: (a) Education of Public and/or Health Care Providers (n = 80, 52 %), (b) Population‐Based Screening Programs (n = 70, 45 %), (c) Lobbying/Public Policy (n = 62, 40 %), (d) Public Health Related Research (n = 47, 30 %), and (e) State Chronic Disease Programs (n = 12, 8 %). Regardless of category, “on the job” was the most common primary source of learning. Genetic counseling training program was the most common secondary source of learning. Results indicate that the number of genetic counselors performing public health activities is likely higher than PSS reports, and that those who may not consider themselves “public health genetic counselors” do participate in public health activities. Genetic counselors learn a diverse skill set in their training programs; some skills are directly applicable to public health genetics, while other public health skills require additional training and/or knowledge.
Testing for Hereditary Breast Cancer: Panel or Targeted Testing? Experience from a Clinical Cancer Genetics Practice
Authors: Doherty Jennifer , Bonadies Danielle C. , Matloff Ellen T. 
Published: December 2014

AbstractApproaches to hereditary breast cancer testing are shifting as multi‐gene panels become more widely available. This paper describes our center's experience and outcomes of a 6‐gene panel test as a first‐tier approach in patients who were candidates for BRCA testing. Between July and December 2013, a 6‐gene panel test was ordered for patients meeting criteria for BRCA testing. A retrospective review detailed the mutation and variant of uncertain significance (VUS) rates for the genes analyzed. The mutation rate was 5.2 % (n = 7) and the VUS rate was 6.7 % (n = 9). A subsequent review determined the number of BRCA‐negative patients who would have been offered additional single gene testing had BRCA, only, been their first‐tier test. Applying consensus criteria revealed 7.1 % (n = 9) cases that met criteria for additional testing. Pedigree analysis by a certified genetic counselor revealed 26.8 % (n = 34) cases that would have been offered additional testing based on personal and/or family history. Our results suggest that this panel may be warranted as a first‐tier test for a small subset of patients, but likely represents over testing for the majority of patients who are candidates for BRCA testing. The genes selected for panels, the extra costs per patient and the chance of VUS must be considered before we uniformly switch from BRCA to full panel testing on all patients.
Perceptions of Latinas on the Traditional Prenatal Genetic Counseling Model
Authors: Thompson Stephanie , Noblin Sarah Jane , Lemons Jennifer , Peterson Susan K. , Carreno Carlos , Harbison Andrea 
Published: December 2014

AbstractThe traditional genetic counseling model encompasses an individualized counseling session that includes the presentation of information about genes, chromosomes, personalized risk assessment, and genetic testing and screening options. Counselors are challenged to balance the provision of enough basic genetic information to ensure clients’ understanding of the genetic condition in question with a personalized discussion of what this information means to them. This study explored the perceptions Latinas have about prenatal genetic counseling sessions and aimed to determine if they had preferences about the delivery of care. Data were collected through focus groups and one‐on‐one, semi‐structured interviews of 25 Spanish speaking Latinas who received genetic counseling during their current pregnancy. We implemented grounded theory to evaluate participant responses, and were able to identify common emergent themes. Several themes were identified including an overall satisfaction with their prenatal genetic counseling appointment, desire for a healthy baby, peace of mind following their appointment, lack of desire for invasive testing, and faith in God. Several participants stated a preference for group genetic counseling over the traditional individual genetic counseling model. Our data indicate that Latinas value the information presented at prenatal genetic counseling appointments despite disinterest in pursuing genetic testing or screening and suggest that group prenatal genetic counseling may be an effective alternative to the traditional genetic counseling model in the Latina population.
Computerised cognitive behavioural therapy for alcohol use disorder: a pilot randomised control trial
Authors: Farren C. K. , Milnes J. , Lambe K. , Ahern S. 
Published: December 2014

BackgroundCognitive behavioural therapy (CBT) has been used in the treatment of alcohol use disorder (AUD), generally in individual or group therapy, but not via computer.AimThis study examined the effectiveness of an interactive, personalised, computer-based CBT therapy in a randomised control trial.MethodsWe studied a group of 55 patients with AUD, randomised to either 5-hour-long computerised CBT sessions or a placebo cognitive-stimulating session, together with a 4-week inpatient rehabilitation treatment, and followed them for 3 months.ResultsThere was a high degree of patient adherence to the protocol. Both groups did well, with a significant fall in alcohol outcome measures including number of drinks per drinking day, and number of drinking days, and an increase in abstinence rates in both groups to an equivalent level. The CBT group attended alcoholics anonymous groups more frequently, and had significant alterations in their alcohol self-efficacy outcomes, which correlated with their drinking outcomes. We concluded that computerised CBT is a potentially useful clinical tool that warrants further investigation in different treatment settings for AUD.
Peripheral blood mononuclear cell gene expression profile in obese boys who followed a moderate energy-restricted diet: differences between high and low responders at baseline and after the intervention
Authors: Rendo-Urteaga Tara , García-Calzón Sonia , González-Muniesa Pedro , Milagro Fermín I. , Chueca María , Oyarzabal Mirentxu , Azcona-Sanjulián M. Cristina , Martínez J. Alfredo , Marti Amelia 
Published: December 2014

The present study analyses the gene expression profile of peripheral blood mononuclear cells (PBMC) from obese boys. The aims of the present study were to identify baseline differences between low responders (LR) and high responders (HR) after 10 weeks of a moderate energy-restricted dietary intervention, and to compare the gene expression profile between the baseline and the endpoint of the nutritional intervention. Spanish obese boys (age 10–14 years) were advised to follow a 10-week moderate energy-restricted diet. Participants were classified into two groups based on the association between the response to the nutritional intervention and the changes in BMI standard deviation score (BMI-SDS): HR group (n 6), who had a more decreased BMI-SDS; LR group (n 6), who either maintained or had an even increased BMI-SDS. The expression of 28 869 genes was analysed in PBMC from both groups at baseline and after the nutritional intervention, using the Affymetrix Human Gene 1.1 ST 24-Array plate microarray. At baseline, the HR group showed a lower expression of inflammation and immune response-related pathways, which suggests that the LR group could have a more developed pro-inflammatory phenotype. Concomitantly, LEPR and SIRPB1 genes were highly expressed in the LR group, indicating a tendency towards an impaired immune response and leptin resistance. Moreover, the moderate energy-restricted diet was able to down-regulate the inflammatory ‘mitogen-activated protein kinase signalling pathway’ in the HR group, as well as some inflammatory genes (AREG and TNFAIP3). The present study confirms that changes in the gene expression profile of PBMC in obese boys may help to understand the weight-loss response. However, further research is required to confirm these findings.
Syndromic surveillance of influenza activity in Sweden: an evaluation of three tools
Authors: MA T. , ENGLUND H. , BJELKMAR P. , WALLENSTEN A. , HULTH A. 
Published: December 2014

SUMMARYAn evaluation was conducted to determine which syndromic surveillance tools complement traditional surveillance by serving as earlier indicators of influenza activity in Sweden.Web queries, medical hotline statistics, andschool absenteeism datawere evaluated against two traditional surveillance tools. Cross-correlation calculations utilized aggregated weekly data for all-age, nationwide activity for four influenza seasons, from 2009/2010 to 2012/2013. The surveillance tool indicative of earlier influenza activity, by way of statistical and visual evidence, was identified. The web query algorithm and medical hotline statistics performed equally well as each other and to the traditional surveillance tools. School absenteeism data were not reliable resources for influenza surveillance. Overall, the syndromic surveillance tools did not perform with enough consistency in season lead nor in earlier timing of the peak week to be considered as early indicators. They do, however, capture incident cases before they have formally entered the primary healthcare system.