bluuebunny/crossref_metadata_2025 huggingface dataset:
Delineation of Crohn’s Disease Trajectories Using Change in Lémann Index
Authors: Bhagya Rao Bhavana , Koutroubakis Ioannis E. , Ramos Rivers Claudia , Colombel Jean Frederic , Regueiro Miguel , Swoger Jason , Schwartz Marc , Baidoo Leonard , Hashash Jana , Barrie Arthur , Dunn Michael A. , Binion David G.
Published: December 2015

Background:

Crohn’s disease (CD) causes lifelong, progressive bowel damage, which may be quantified using the Lémann Index (LI). We aimed to analyze patterns of LI and its association with 5-year clinical course, in an independent cohort of CD patients.

Methods:

CD patients with 5-year follow-up from a registry maintained at a tertiary center were included. LI was calculated using a computerized metric from the first (LI1) and last (LI2) clinical encounters during the 5 years. Groups were created based on change in score (LI2-LI1) or the delta Lémann Index (DLI) as showing improvement, no change, or deterioration and used for association analysis with patterns of health care utilization, disease activity, and quality-of-life scores.

Results:

A total of 363 CD patients with 5-year follow-up formed the study population [median age 43 y (interquartile range (IQR), 33.3 to 55 y); 57% female; median disease duration 12 y (IQR, 3 to 19 y), overall surgical exposure 69.7%]. Median (IQR) LI1, LI2, and DLI were 8 (0 to 54), 9 (0 to 75), and 0 (−22 to –47), respectively. Patients were stratified based on DLI into 3 groups: A: DLI<0; B: DLI=0; and C: DLI>0; which comprised 16.5%, 35.3%, and 48.2% of the cohort, respectively. Patients in group C had significantly higher CD-related surgical exposure, health care utilization, and annual use of steroids and biological agents. DLI showed independent significant positive correlation with perianal disease (P=0.044), steroid use (P=0.007), clinical visits (P<0.001), and new surgeries (P=0.001).

Conclusions:

Change in LI over time could function as a marker of disease trajectory for risk substratification and prognostication in CD.
Do we need demographic data to forecast plant population dynamics?
Authors: Tredennick Andrew T. , Hooten Mevin B. , Adler Peter B.
Published: December 2015

Rapid environmental change has generated growing interest in forecasts of future popu lation trajectories. Traditional population models built with detailed demographic obser vations from one study site can address the impacts of environmental change at particular locations, but are difficult to scale up to the landscape and regional scales relevant to man agement decisions. An alternative is to build models using population-level data that are much easier to collect over broad spatial scales than individual-level data. However, it is unknown whether models built using population-level data adequately capture the effects of density-dependence and environmental forcing that are necessary to generate skillful forecasts.

Here, we test the consequences of aggregating individual 29 responses when forecasting the population states (percent cover) and trajectories of four perennial grass species in a semi-arid grassland in Montana, USA. We parameterized two population models for each species, one based on individual-level data (survival, growth and recruitment) and one on population-level data (percent cover), and compared their forecasting accuracy and fore cast horizons with and without the inclusion of climate covariates. For both models, we used Bayesian ridge regression to weight the influence of climate covariates for optimal prediction.

In the absence of climate effects, we found no significant difference between the forecast accuracy of models based on individual-level data and models based on population-level data. Climate effects were weak, but increased forecast accuracy for two species. Increases in accuracy with climate covariates were similar between model types.

In our case study, percent cover models generated forecasts as accurate as those from a demographic model. For the goal of forecasting, models based on aggregated individual level data may offer a practical alternative to data-intensive demographic models. Long time series of percent cover data already exist for many plant species. Modelers should exploit these data to predict the impacts of environmental change.
The Ionotropic Receptors IR21a and IR25a mediate cool sensing inDrosophila
Authors: Ni Lina , Klein Mason , Svec Kathryn , Budelli Gonzalo , Chang Elaine C. , Benton Richard , Samuel Aravinthan D. T. , Garrity Paul A.
Published: December 2015

Animals rely on highly sensitive thermoreceptors to seek out optimal temperatures, but the molecular mechanisms of thermosensing are not well understood. The Dorsal Organ Cool Cells (DOCCs) of theDrosophilalarva are a set of exceptionally thermosensitive neurons critical for larval cool avoidance. Here we show that DOCC cool-sensing is mediated by Ionotropic Receptors (IRs), a family of sensory receptors widely studied in invertebrate chemical sensing. We find that two IRs, IR21a and IR25a, are required to mediate DOCC responses to cooling and are required for cool avoidance behavior. Furthermore, we find that ectopic expression of IR21a can confer cool-responsiveness in anIr25a-dependent manner, suggesting an instructive role for IR21a in thermosensing. Together, these data show that IR family receptors can function together to mediate thermosensation of exquisite sensitivity.
Extreme positive allometry of animal adhesive pads and the size limits of adhesion-based climbing.
Authors: Labonte David , Clemente Christofer J , Dittrich Alex , Kuo Chi-Yun , Crosby Alfred J , Irschick Duncan J , Federle Walter
Published: December 2015

Organismal functions are size-dependent whenever body surfaces supply body volumes. Larger organisms can develop strongly folded internal surfaces for enhanced diffusion, but in many cases areas cannot be folded so that their enlargement is constrained by anatomy, presenting a problem for larger animals. Here, we study the allometry of adhesive pad area in 225 climbing animal species, covering more than seven orders of magnitude in weight. Across all taxa, adhesive pad area showed extreme positive allometry and scaled with weight, implying a 200-fold increase of relative pad area from mites to geckos. However, allometric scaling coefficients for pad area systematically decreased with taxonomic level, and were close to isometry when evolutionary history was accounted for, indicating that the substantial anatomical changes required to achieve increases in relative pad area are limited by phylogenetic constraints. Using a comparative phylogenetic approach, we found that the departure from isometry is almost exclusively caused by large differences in size-corrected pad area between arthropods and vertebrates. To mitigate the expected decrease of weight-specific adhesion within closely related taxa where pad area scaled close to isometry, data for several taxa suggest that the pads' adhesive strength increased for larger animals. The combination of adjustments in relative pad area for distantly related taxa and changes in adhesive strength for closely related groups helps explain how climbing with adhesive pads has evolved in animals varying over seven orders of magnitude in body weight. Our results illustrate the size limits of adhesion-based climbing, with profound implications for large-scale bio-inspired adhesives.
On the Apportionment of Population Structure
Authors: Granot Yaron , Tal Omri , Rosset Saharon , Skorecki Karl
Published: December 2015

Measures of population differentiation, such as FST, are traditionally derived from the partition of diversity within and between populations. However, the emergence of population clusters from multilocus analysis is a function of geneticstructure(departures from panmixia) rather than of diversity. If the populations are close to panmixia, slight differences between the mean pairwise distance within and between populations (low FST) can manifest as strong separation between the populations, thus population clusters are often evident even when the vast majority of diversity is partitioned within populations rather than between them. For any given FSTvalue, clusters can be tighter (more panmictic) or looser (more stratified), and in this respect higher FSTdoes not always imply stronger differentiation. In this study we propose a measure for the partition of structure, denoted EST, which is more consistent with results from clustering schemes. Crucially, our measure is based on a statistic of the data that is a good measure of internal structure, mimicking the information extracted by unsupervised clustering or dimensionality reduction schemes. To assess the utility of our metric, we ranked various human (HGDP) population pairs based on FSTand ESTand found substantial differences in ranking order. In some cases examined, most notably among isolated Amazonian tribes, ESTranking seems more consistent with demographic, phylogeographic and linguistic measures of classification compared to FST. Thus, ESTmay at times outperform FSTin identifying evolutionary significant differentiation.
Fitness effects of new mutations inChlamydomonas reinhardtiiacross two stress gradients
Authors: Kraemer Susanne A. , Morgan Andrew D. , Ness Robert W. , Keightley Peter D. , Colegrave Nick
Published: December 2015

Most spontaneous mutations affecting fitness are likely to be deleterious, but the strength of selection acting on them might be impacted by environmental stress. Such stress-dependent selection could expose hidden genetic variation, which in turn might increase the adaptive potential of stressed populations. On the other hand, this variation might represent a genetic load and thus lead to population extinction under stress. Previous studies to determine the link between stress and mutational effects on fitness, however, have produced inconsistent results. Here, we determined the net change in fitness in 29 genotypes of the green algaeChlamydomonas reinhardtiithat accumulated mutations in the near absence of selection for approximately 1,000 generations across two stress gradients, increasing NaCl and decreasing phosphate. We found mutational effects to be magnified under extremely stressful conditions, but such effects were specific both to the type of stress as well as to the genetic background. The detection of stress-dependent fitness effects of mutations depended on accurately scaling relative fitness measures by generation times, thus offering an explanation for the inconsistencies among previous studies.
Modeling Continuous Admixture
Authors: Zhou Ying , Qiu Hongxiang , Xu Shuhua
Published: December 2015

Human migration and human isolation serve as the driving forces of modern human civilization. Recent migrations of long isolated populations have resulted in genetically admixed populations. The history of population admixture is generally complex; however, understanding the admixture process is critical to both evolutionary and medical studies. Here, we utilized admixture induced linkage disequilibrium (LD) to infer occurrence of continuous admixture events, which is common for most existing admixed populations. Unlike previous studies, we expanded the typical continuous admixture model to a more general admixture scenario with isolation after a certain duration of continuous gene flow. Based on the extended models, we developed a method based on weighted LD to infer the admixture history considering continuous and complex demographic process of gene flow between populations. We evaluated the performance of the method by computer simulation and applied our method to real data analysis of a few well-known admixed populations.
X-ray characterization of a multichannel smart-pixel array detector
Authors: Ross Steve , Haji-Sheikh Michael , Huntington Andrew , Kline David , Lee Adam , Li Yuelin , Rhee Jehyuk , Tarpley Mary , Walko Donald A. , Westberg Gregg , Williams George , Zou Haifeng , Landahl Eric
Published: December 2015

The Voxtel VX-798 is a prototype X-ray pixel array detector (PAD) featuring a silicon sensor photodiode array of 48 × 48 pixels, each 130 µm × 130 µm × 520 µm thick, coupled to a CMOS readout application specific integrated circuit (ASIC). The first synchrotron X-ray characterization of this detector is presented, and its ability to selectively count individual X-rays within two independent arrival time windows, a programmable energy range, and localized to a single pixel is demonstrated. During our first trial run at Argonne National Laboratory's Advance Photon Source, the detector achieved a 60 ns gating time and 700 eV full width at half-maximum energy resolution in agreement with design parameters. Each pixel of the PAD holds two independent digital counters, and the discriminator for X-ray energy features both an upper and lower threshold to window the energy of interest discarding unwanted background. This smart-pixel technology allows energy and time resolution to be set and optimized in software. It is found that the detector linearity follows an isolated dead-time model, implying that megahertz count rates should be possible in each pixel. Measurement of the line and point spread functions showed negligible spatial blurring. When combined with the timing structure of the synchrotron storage ring, it is demonstrated that the area detector can perform both picosecond time-resolved X-ray diffraction and fluorescence spectroscopy measurements.
Quick AS NEXAFS Tool(QANT): a program for NEXAFS loading and analysis developed at the Australian Synchrotron
Authors: Gann Eliot , McNeill Christopher R. , Tadich Anton , Cowie Bruce C. C. , Thomsen Lars
Published: December 2015

An analysis program for near-edge X-ray absorption fine-structure (NEXAFS) spectra has been developed and implemented at the soft X-ray beamline of the Australian Synchrotron. The program allows for instant viewing of corrected data channels including normalizations to a standard, double normalizations when the standard itself has an undesired spectral response, and background subtraction. The program performs simple compositional analysis and peak fitting and includes rapid common calculations such as the average tilt angle of molecules with respect to the surface, and the determination of the complex index of refraction, which previously required intensive manual analysis. These functionalities make common manipulations carried out with NEXAFS data quick and straightforward as spectra are collected, greatly increasing the efficiency and overall throughput of NEXAFS experiments.
Crystal structure of benzobicyclon
Authors: Kang Gihaeng , Kim Jineun , Lim Hansu , Kim Tae Ho
Published: December 2015

In the title compound, C22H19ClO4S2[systematic name: 3-(2-chloro-4-mesylbenzoyl)-4-(phenylsulfanyl)bicyclo[3.2.1]oct-3-en-2-one], which is an unclassified herbicide, the dihedral angle between the plane of the phenyl and chlorobenzene rings is 19.9 (2)°. In the crystal, C—H...O hydrogen bonds link adjacent molecules, generating two-dimensional networks extending parellel to (011).
Crystal structure of 5-[4-(dimethylamino)phenyl]-3-(4-methylphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde
Authors: Adam Farook , Samshuddin Seranthimata , Ameram Nadiah , Subramaya  , Samartha Laxminarayana
Published: December 2015

The title compound, C19H21N3O, comprises a central pyrazole ring which is N-connected to an aldehyde group and C-connected twice to substituted benzene rings. The pyrazole ring is twisted on the C—C single bond, and the least-squares plane through this ring forms dihedral angles of 82.44 (5) and 4.52 (5)° with the (dimethylamino)benzene andp-tolyl rings, respectively. In the crystal, weak C—H...O hydrogen bonds link molecules into supramolecular tubes along thebaxis.
Evaluation of electronic service infrastructures and quality of e-services in Nigerian academic libraries
Authors: Asogwa Brendan E. , Ugwu Cyprian I. , Ugwuanyi Ferdinand C.
Published: December 2015

Purpose

– The purpose of this paper is to evaluate the quality of online services in academic libraries in Nigeria. It seeks to assess the functionality of electronic infrastructures, to expose areas where the service needs of users are not adequately provided and to recommend solutions.

Design/methodology/approach

– The sample population was 210 staff and students who used electronic resources in Nigerian university libraries during the 2012-2013 academic session. A questionnaire was the main instrument for data collection. Modified WebQual four performance indicators were designed and used to measure: library equipment, library website, online public access catalogue (OPAC) and e-user education in the university libraries. The five-point service performance scale that ranged from very poor performance to excellent was used in measuring the views of the respondents.

Findings

– None of the indicators was rated excellent; six were rated good; nine were average; two and five indicators scored poor and very poor, respectively. Poor funding, intermittent power supply and weak telecommunication infrastructures were among the major impediments to online services in Nigerian universities. Through adequate funding and prudent management of library funds, online services in Nigerian university libraries could meet global standards.

Practical implications

– Results from this paper could guide library management on several concrete remedial actions to sustain e-service performance that could meet the missions and visions of contemporary academic libraries.

Originality/value

– This paper was the first to apply WebQual model in the evaluation of electronic performance quality of academic libraries in Nigeria.
Photosystem‐II shutdown evolved with Nitrogen fixation in the unicellular diazotroph Crocosphaera watsonii
Authors: Rabouille Sophie , Claquin Pascal
Published: December 2015

Protection of nitrogenase from oxygen in unicellular Cyanobacteria is obtained by temporal separation of photosynthesis and diazotrophy through transcriptional and translational regulations of nitrogenase. But diazotrophs can face environmental situations in which N2 fixation occurs significantly in the light, and we believe that another control operates to make it possible. The night‐time shutdown of PSII activity is a peculiar behaviour that discriminates Crocosphaera watsonii WH8501 from any other phototroph, whether prokaryote or eukaryote. This phenomenon is not only due to the plastoquinone pool redox status, and suggests that the sentinel D1 protein, expressed in periods of nitrogen fixation, is inactive. Results demonstrate a tight constraint of oxygen evolution in C. watsonii as additional protection of nitrogenase activity and suggest a possible recycling of cellular components.
Intergovernmental Fiscal Transfers and Local Incentives and Responses: The Case of Indonesia
Authors: Lewis Blane D. , Smoke Paul
Published: December 2015

Indonesian policymakers are convinced that a number of perverse incentives are embedded in their system of intergovernmental transfers. Officials in countries throughout the developing world have similar views about their own intergovernmental frameworks. In Indonesia, perverse incentives are thought to negatively influence a wide range of local government fiscal behaviours, including as regards own‐source revenues, spending and savings. An empirical analysis of the local government response to transfers, however, offers only mixed support for the existence and strength of the presumed incentives. Overall, the findings in this paper highlight the benefits to central governments of rigorously examining assumed perverse incentives in their intergovernmental frameworks before embarking on attempts to expunge them.
Tropically adapted cattle of Africa: perspectives on potential role of copy number variations
Authors: Wang M. D. , Dzama K. , Rees D. J. G. , Muchadeyi F. C.
Published: December 2015

Africa is host to diverse and locally adapted cattle breeds that are expected to survive the harsh and extreme tropical environments associated with diseases and parasite infections, heat stress and episodes of feed and water scarcity. Genomic copy number variations (CNVs) are considered to be primary role players in cattle breed formation and adaptation where isolation and genetic drift together with subsequent mutations have created an enormous diversity of local populations. CNVs are modifications in DNA structure comprising deletions, duplications and insertions that are >1 kb in size. Despite attracting much attention, the frequency and pattern of bovine CNV events, especially in African cattle breeds, are for the most part largely unknown. Characterization of genetic variation in the indigenous cattle of Africa will be a vital step toward dissecting the molecular mechanisms underlying phenotypic variation and local adaptation. This review therefore aims to describe the current knowledge regarding bovine CNVs and the implications and potentials they encompass for dissecting genetic adaptation and the genotypic skeleton of tropical African cattle populations.
Communication skills training enhances nurses' ability to respond with empathy to parents' emotions in a neonatal intensive care unit
Authors: Bry Kristina , Bry Maija , Hentz Elisabet , Karlsson Håkan L. , Kyllönen Hanna , Lundkvist Malin , Wigert Helena
Published: December 2015

Aim

We quantitatively analysed the effect of a course in communication on the content of nurse–parent encounters and the ability of nurses to respond to the empathic needs of parents in a level III neonatal intensive care unit.

Methods

We evaluated 36 and 45 nurse–parent encounters audio recorded before and after 13 neonatal nurses attended a communication course. The number of empathic opportunities, the nurses' responses to these and the ways they involved parents in their infants' care were studied.

Results

Both before and after the course, the nurses talked more than the parents during the conversations. This nurse‐centredness decreased after the course. The use of empathic or exploring responses to empathic opportunities increased from 19.9 ± 9.0% to 53.8 ± 8.9% (p = 0.027), whereas ignoring the feelings of the parents or giving inadequate advice decreased from 63.0 ± 10.0% to 27.5 ± 8.4% (p = 0.043) after the course. Use of statements expressing caring for the parents and encouragement for parents to participate in the care of their infant increased after the course (p = 0.0034 and p = 0.043, respectively). The nurses felt the course was very useful for their profession.

Conclusion

A course in communication techniques improved nurses' ability to respond to parents' feelings with empathy.
Purinergic receptor blockade in the retrotrapezoid nucleus attenuates the respiratory chemoreflexes in awake rats
Authors: Barna B. F. , Takakura A. C. , Mulkey D. K. , Moreira T. S.
Published: December 2015

Aim

Recent evidence suggests that adenosine triphosfate (ATP)‐mediated purinergic signalling at the level of the rostral ventrolateral medulla contributes to both central and peripheral chemoreceptor control of breathing and blood pressure: neurones in the retrotrapezoid nucleus (RTN) function as central chemoreceptors in part by responding to CO2‐evoked ATP release by activation of yet unknown P2 receptors, and nearby catecholaminergic C1 neurones regulate blood pressure responses to peripheral chemoreceptor activation by a P2Y1 receptor‐dependent mechanism. However, potential contributions of purinergic signalling in the RTN to cardiorespiratory function in conscious animals have not been tested.

Methods

Cardiorespiratory activity of unrestrained awake rats was measured in response to RTN injections of ATP, and during exposure to hypercapnia (7% CO2) or hypoxia (8% O2) under control conditions and after bilateral RTN injections of P2 receptor blockers (PPADS or MRS2179).

Results

Unilateral injection of ATP into the RTN increased cardiorespiratory output by a P2‐recepor‐dependent mechanism. We also show that bilateral RTN injections of a non‐specific P2 receptor blocker (pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulfonate (PPADS) reduced the ventilatory response to hypercapnia (7% CO2) and hypoxia (8% O2) in unanesthetized rats. Conversely, bilateral injections of a specific P2Y1 receptor blocker (MRS2179) into the RTN had no measurable effect on ventilatory responses elicited by hypercapnia or hypoxia.

Conclusion

These data exclude P2Y1 receptor involvement in the chemosensory control of breathing at the level of the RTN and show that ATP‐mediated purinergic signalling contributes to central and peripheral chemoreflex control of breathing and blood pressure in awake rats.
‘But what do you measure?’ Prospects for a constructive critical physical geography
Authors: Blue Brendon , Brierley Gary
Published: December 2015

Geomorphology shapes the way we perceive the world around us, making certain ways of understanding and interacting with landscapes more possible than others. Despite this, geomorphologists have a reputation for not engaging with philosophical questions regarding their work, particularly the role of theory, framing and language. Recent calls for a critical physical geography present significant opportunities for physical geographers to engage with questions that often go unasked, and unanswered, in the Earth sciences. Here we discuss what a critical physical geography might bring to geomorphology, examining the implications of what we measure in our efforts to classify and understand river form and process. While geomorphology benefits from using the approaches and methods of science, it struggles with the fundamental problem of closure. Through the example of river diversity we explore how our decisions, tools and knowledge frameworks shape environmental outcomes. We challenge the assumption that once a landscape is measured it is ‘known’, and argue for geomorphologists to actively explore alternative ways of knowing the landscape towards a discipline which is both more just and more scientific. We imagine an inclusive critical physical geography, drawing on disparate theoretical approaches to constructively critique the practice of geomorphology. We argue that this engagement will be most productive if it is framed in a readily accessible manner. Negotiating such a project is undoubtedly challenging, but there is more to be gained by building bridges over the science/humanities divide than by shouting across it.
Can people talk together about their practices? Focus groups, humour and the sensitive dynamics of everyday life
Authors: Browne Alison L
Published: December 2015

The exploration of everyday social practices related to sustainability often touches on the most invisible parts of people's everyday lives. Given the multiple cultural forces that govern cleanliness and comfort, and the intimate spheres in which these practices are performed, practices associated with everyday water use (and associated energy consumption) bump up against ‘the taboo’. While it has been resolved that ‘people can talk about their practices’ in interviews, a range of other methods – including CCTV, video and other data to survey and document practices in homes – are increasingly being used. As we delve theoretically closer to these public/private boundaries with new studies on social practices and sustainability, greater attention to the ethics of methods is needed. Different ‘talk'‐based methodologies such as focus groups that could allow researchers to work more ethically with the strong moral sensitivities of certain domestic practices have not yet been considered. This paper explores six focus groups on ‘bodies, clothes, dirt and cleanliness’ that took place in Lancaster, UK. Reflecting on researcher positionality, and results of a follow‐up survey with participants, the paper concludes that focus groups, humour and laughter enable intimately political conversations about aspects of everyday practices that might be difficult to access or articulate through other research methods. The implications of using conversational humour and laughter as purposeful tools for exploring particular aspects of everyday social practices is also explored. This paper responds to recent calls for greater consideration of fieldwork and methodologies related to gender and embodiment within human geography, and on the ethics and politics of everyday life research.
A New, Improved Hybrid Scoring Function for Molecular Docking and Scoring Based on AutoDock and AutoDock Vina
Authors: Tanchuk Vsevolod Yu , Tanin Volodymyr O. , Vovk Andriy I. , Poda Gennady
Published: December 2015

Automated docking is one of the most important tools for structure‐based drug design that allows prediction of ligand binding poses and also provides an estimate of how well small molecules fit in the binding site of a protein. A new scoring function based on AutoDock and AutoDock Vina has been introduced. The new hybrid scoring function is a linear combination of the two scoring function components derived from a multiple linear regression fitting procedure. The scoring function was built on a training set of 2412 protein–ligand complexes from pdbbind database (www.pdbbind.org.cn, version 2012). A test set of 313 complexes that appeared in the 2013 version was used for validation purposes. The new hybrid scoring function performed better than the original functions, both on training and test sets of protein–ligand complexes, as measured by the non‐parametric Pearson correlation coefficient, R, mean absolute error (MAE), and root‐mean‐square error (RMSE) between the experimental binding affinities and the docking scores. The function also gave one of the best results among more than 20 scoring functions tested on the core set of the pdbbind database. The new AutoDock hybrid scoring function will be implemented in modified version of AutoDock.
68Ga‐labeled Ciprofloxacin Conjugates as Radiotracers for Targeting Bacterial Infection
Authors: Satpati Drishty , Arjun Chanda , Krishnamohan Repaka , Samuel Grace , Banerjee Sharmila
Published: December 2015

With an aim of developing a bacteria‐specific molecular imaging agent, ciprofloxacin has been modified with a propylamine spacer and linked to two common bifunctional chelators, p‐SCN‐Bz‐DOTA and p‐SCN‐Bz‐NOTA. The two ciprofloxacin conjugates, CP‐PA‐SCN‐Bz‐DOTA (1) and CP‐PA‐SCN‐Bz‐NOTA (2), were radiolabeled with 68Ga in >90% radiochemical yield and were moderately stable in vitro for 4 h. The efficacy of 68Ga‐1 and 68Ga‐2 has been investigated in vitro in Staphylococcus aureus cells where bacterial binding of the radiotracers (0.9–1.0% for 68Ga‐1 and 1.6–2.3% for 68Ga‐2) could not be blocked in the presence of excess amount of unlabeled ciprofloxacin. However, uptake of radiotracers in live bacterial cells was significantly higher (p < 0.01) than that in non‐viable bacterial cells. Bacterial infection targeting efficacy of 68Ga‐1 and 68Ga‐2 was tested in vivo in rats where the infected muscle‐to‐inflamed muscle (68Ga‐1: 2 ± 0.2, 68Ga‐2: 3 ± 0.5) and infected muscle‐to‐normal muscle ratios (68Ga‐1: 3 ± 0.4, 68Ga‐2: 6.6 ± 0.8) were found to improve at 120 min p.i. Fast blood clearance and renal excretion was observed for both the radiotracers. The two 68Ga‐labeled infection targeting radiotracers could discriminate between bacterial infection and inflammation in vivo and are worthy of further detailed investigation as infection imaging agents at the clinical level.
GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy
Authors: Papandreou Apostolos , McTague Amy , Trump Natalie , Ambegaonkar Gautam , Ngoh Adeline , Meyer Esther , Scott Richard H , Kurian Manju A
Published: December 2015

The gamma‐aminobutyric acid type A receptor β3 gene (GABRB3) encodes the β3‐subunit of the gamma‐aminobutyric acid type A (GABAA) receptor, which mediates inhibitory signalling within the central nervous system. Recently, GABRB3 mutations have been identified in a few patients with infantile spasms and Lennox–Gastaut syndrome. We report the clinical and electrographic features of a novel case of GABRB3‐related early‐onset epileptic encephalopathy. Our patient presented with neonatal hypotonia and feeding difficulties, then developed pharmacoresistant epileptic encephalopathy, characterized by multiple seizure types from 3 months of age. Electroencephalography demonstrated ictal generalized and interictal multifocal epileptiform abnormalities. Using a SureSelectXT custom multiple gene panel covering 48 early infantile epileptic encephalopathy/developmental delay genes, a novel de novo GABRB3 heterozygous missense mutation, c.860C>T (p.Thr287Ile), was identified and confirmed on Sanger sequencing. GABRB3 is an emerging cause of early‐onset epilepsy. Novel genetic technologies, such as whole‐exome/genome sequencing and multiple gene panels, will undoubtedly identify further cases, allowing more detailed electroclinical delineation of the GABRB3‐related genotypic and phenotypic spectra.
Clinical impact of BRAF mutation on the diagnosis and prognosis of papillary thyroid carcinoma: a systematic review and meta‐analysis
Authors: Wang Zhen , Chen Jun‐Qiang , Liu Jin‐Lu , Qin Xin‐Gan
Published: December 2015

Background

The possible role of BRAFV600E mutation in the diagnosis and prognosis of papillary thyroid carcinoma (PTC) remains controversial. A systematic review to investigate the diagnostic and prognostic role of BRAFV600E mutation in patients with PTC is urgently needed.

Methods

A systematic review of relevant literatures was performed in PubMed, EMBASE and CENTRAL. The incremental accuracy (IA) of fine needle aspiration biopsy plus BRAFV600E mutation analysis over fine needle aspiration biopsy alone, and the statistical data about the association of BRAFV600E mutation and the prognosis of PTC (risk ratios (RR) for dichotomous data, standard mean differences for continuous data and hazard ratios (HRs) for disease‐free survival (DFS) were pooled. Subgroup analysis was performed to explain the heterogeneities.

Results

A total of 67 studies were included. The pooled IA was 2% (95% confidence interval (CI): 0·5–4%). The pooled RR for gender, multifocality, lymph node metastasis, extrathyroidal invasion and pathological stage was 1·11 (95% CI: 0·98–1·25), 1·17 (95% CI: 1·09–1·24), 1·36 (95% CI: 1·20–1·53), 1·60 (95% CI: 1·41–1·82), and 1·49 (95% CI: 1·33–1·68), respectively. The pooled standard mean differences for age and tumour size were 0·14 (95% CI: 0·04–0·23) and 0·21 (95% CI: 0·1–0·32), respectively. The pooled HR for DFS was 1·96 (95% CI: 1·62–2·37). Subgroup analysis showed that these statistical results were affected by the geographical background of patients, study design and detection methods.

Conclusions

BRAFV600E mutation analysis can not only be used in the diagnosis of PTC, but can also predict its prognosis.
INEQUALITY AND TRUST: NEW EVIDENCE FROM PANEL DATA
Authors: Barone Guglielmo , Mocetti Sauro
Published: December 2015

We estimate the causal link from income inequality to generalized trust by reconsidering the country‐level evidence on this issue. First, we exploit the panel dimension of the data, thus controlling for any country unobservable time‐invariant variables, and find a negative relationship between the two variables that holds only for developed countries. Second, we focus on these advanced economies and provide instrumental variable estimates using the predicted exposure to technological change as an exogenous driver of inequality. According to our findings, the negative causal effect of inequality on trust is even larger than that coming from ordinary least squares estimation. We also provide new insights on the effects of different dimensions of inequality, exploiting measures of bothstaticinequality—such as the Gini index and top income shares—anddynamicinequality—proxied by intergenerational income mobility. (JELD31, O15, Z13)
Young adults' experiences of seeking online information about diabetes and mental health in the age of social media
Authors: Fergie Gillian , Hilton Shona , Hunt Kate
Published: December 2015

Background

The Internet is a primary source of health information for many. Since the widespread adoption of social media, user‐generated health‐related content has proliferated, particularly around long‐term health issues such as diabetes and common mental health disorders (CMHDs).

Objective

To explore perceptions and experiences of engaging with health information online in a sample of young adults familiar with social media environments and variously engaged in consuming user‐generated content.

Methods

Forty semi‐structured interviews were conducted with young adults, aged 18–30, with experience of diabetes or CMHDs. Data were analysed following a thematic networks approach to explore key themes around online information‐seeking and content consumption practices.

Results

Although participants primarily discussed well‐rehearsed approaches to health information‐seeking online, particularly reliance on search engines, their accounts also reflected active engagement with health‐related content on social media sites. Navigating between professionally produced websites and user‐generated content, many of the young adults seemed to appreciate different forms of health knowledge emanating from varied sources. Participants described negotiating health content based on social media practices and features and assessing content heuristically. Some also discussed habitual consumption of content related to their condition as integrated into their everyday social media use.

Conclusion

Technologies such as Facebook, Twitter and YouTube offer opportunities to consume and assess content which users deem relevant and useful. As users and organizations continue to colonize social media platforms, opportunities are increasing for health communication and intervention. However, how such innovations are adopted is dependent on their alignment with users' expectations and consumption practices.
Whole‐mount pathology of breast lumpectomy specimens improves detection of tumour margins and focality
Authors: Clarke Gina M , Holloway Claire M B , Zubovits Judit T , Nofech‐Mozes Sharon , Liu Kela , Murray Mayan , Wang Dan , Yaffe Martin J
Published: December 2015

Aims

Technical limitations in conventional pathological evaluation of breast lumpectomy specimens may reduce diagnostic accuracy in the assessment of margin and focality. A novel technique based on whole‐mount serial sections enhances sampling while preserving specimen conformation and orientation. The aim of this study was to investigate assessment of focality and margin status by the use of whole‐mount serial sections versus simulated conventional sections in lumpectomies.

Methods and results

Two pathologists interpreted whole‐mount serial sections and simulated conventional sections for 58 lumpectomy specimens by reporting the closest margin and focality. Measurements were compared by the use of McNemar's chi‐squared test. Statistically significant differences were observed in the assignment of both margin positivity (P = 0.014) and multifocality (P = 0.021). A positive margin or multifocal disease was identified by the use of whole‐mount serial sections but missed in the simulated conventional assessment in 10.3% and 17.2% of all cases, respectively. There was no case in which a positive margin was detected only in the simulated conventional assessment.

Conclusions

The whole‐mount technique is more sensitive than conventional assessment for identifying a positive margin or multifocal disease in breast lumpectomy specimens. Undersampling in conventional sections was implicated in almost all cases of discordance. The majority of positive margins or secondary foci identified only in whole‐mount serial sections concerned in‐situ disease.
Expression of the voltage‐gated potassium channel Kv3.4 in oral leucoplakias and oral squamous cell carcinomas
Authors: Fernández‐Valle Álvaro , Rodrigo Juan Pablo , García‐Pedrero Juana M , Rodríguez‐Santamarta Tania , Allonca Eva , Lequerica‐Fernández Paloma , de Vicente Juan Carlos
Published: December 2015

Aims

The expression of the voltage‐gated potassium channel Kv3.4 was investigated in both oral squamous cell carcinomas (OSCC) and oral leucoplakias to establish its clinical significance during the development and progression of OSCC.

Materials and methods

Tissue specimens from 62 patients with oral leucoplakia were collected prospectively and 100 patients with OSCC who underwent surgical treatment were collected retrospectively, and Kv3.4 expression was analysed by immunohistochemistry.

Results

Thirty‐nine of 100 tumours exhibited Kv3.4‐positive expression, and staining was associated with the degree of differentiation (P = 0.05) but showed no impact on patient prognosis. Abnormal Kv3.4 expression was detected in 16% (7 of 43) hyperplastic lesions and at a significantly higher proportion in oral dysplasias (50%, 8 of 16 cases; P = 0.008), whereas expression was negligible in normal adjacent epithelia. Furthermore, patients carrying Kv3.4‐positive lesions exhibited a higher progression risk than those with Kv3.4‐negative lesions; however, histology but not Kv3.4 expression predicted oral cancer development significantly in this prospective cohort.

Conclusion

This study provides original evidence to demonstrate the early occurrence and high prevalence of abnormal Kv3.4 expression in oral leucoplakias. Our results support a role for Kv3.4 potassium channel in OSCC tumorigenesis rather than tumour progression and disease outcome.
Baseline abnormal liver function tests are more important than age in the development of isoniazid‐induced hepatoxicity for patients receiving preventive therapy for latent tuberculosis infection
Authors: Gray E. L. , Goldberg H. F.
Published: December 2015

Background

One of the cornerstones of Australia's public health programmes to eliminate tuberculosis (TB) is the identification and treatment of latent tuberculosis infection (LTBI).

Aims

The main aim of this study is to determine the demographics, compliance, completion rates and adverse events of patients on preventive therapy (PT) for LTBI at our institution. The secondary aim is to determine the rates of isoniazid (INH) hepatotoxicity and identify any contributory factors.

Methods

The method used was an audit using medical records of 100 consecutive patients (2010–2014) treated with PT for LTBI.

Results

Seventy‐two patients with confirmed LTBI started 9 months of INH and 22 started 4 months of rifampicin (RIF). The median age was 30 years. Half the patients were born in high TB‐prevalence countries. Fifty‐six per cent were contacts of index cases with confirmed TB, and 26% were pre‐immunosuppression. Seventy‐seven per cent completed PT with adequate compliance. Thirty‐three per cent on INH and 23% on RIF experienced some liver function test (LFT) abnormality while on treatment. INH was ceased in 3% due to asymptomatic hepatic dysfunction (transaminases >5x upper limit of normal). No patients had permanent liver damage. Significant risk factors for liver dysfunction during PT were risk factors for liver disease ( = 8.7; P = 0.03) or abnormal pre‐therapy LFT ( = 22.4; P < 0.001). No patients developed active TB.

Conclusion

The completion rate of 77% and rate of INH‐induced hepatic dysfunction of 3% is comparable with the literature. We found no age association with the risk of INH‐induced hepatic dysfunction; however, there was a significant and linear association with the degree of liver function abnormality during INH therapy and the presence of abnormal baseline LFT. Routine LFT monitoring allowed early cessation of INH in those with significant but asymptomatic hepatitis who did not meet criteria for ATS/CDC LFT monitoring.
Transient receptor potential vanilloid 1 expression and function in splenic dendritic cells: a potential role in immune homeostasis
Authors: Assas Mushref Bakri , Wakid Majed H. , Zakai Haytham A. , Miyan Jaleel A. , Pennock Joanne L.
Published: December 2015

Neuro‐immune interactions, particularly those driven by neuropeptides, are increasingly implicated in immune responses. For instance, triggering calcium‐channel transient receptor potential vanilloid 1 (TRPV1) on sensory nerves induces the release of calcitonin‐gene‐related peptide (CGRP), a neuropeptide known to moderate dendritic cell activation and T helper cell type 1 polarization. Despite observations that CGRP is not confined to the nervous system, few studies have addressed the possibility that immune cells can respond to well‐documented ‘neural’ ligands independently of peripheral nerves. Here we have identified functionally relevant TRPV1 on primary antigen‐presenting cells of the spleen and have demonstrated both calcium influx and CGRP release in three separate strains of mice using natural agonists. Furthermore, we have shown down‐regulation of activation markers CD80/86 on dendritic cells, and up‐regulation of interleukin‐6 and interleukin‐10 in response to CGRP treatment. We suggest that dendritic cell responses to neural ligands can amplify neuropeptide release, but more importantly that variability in CGRP release across individuals may have important implications for immune cell homeostasis.
Job Lock: Evidence from a Regression Discontinuity Design
Authors: Fairlie Robert W. , Kapur Kanika , Gates Susan
Published: December 2015

Employer‐provided health insurance may restrict job mobility, resulting in “job lock.” Previous research on job lock finds mixed results using several methodologies. We take a new approach to examine job lock by exploiting the discontinuity created at age 65 through the qualification for Medicare. Using a novel procedure for identifying age in months from matched monthly Current Population Survey data and a relatively unexplored administration measure of job mobility, we compare job mobility among male workers in the months just prior to turning age 65 to job mobility in the months just after turning age 65. We find no evidence that job mobility increases at the age 65 threshold when Medicare eligibility starts. We also do not find evidence that other factors such as retirement, reduction in hours worked, Social Security eligibility, pension eligibility, and sample changes confound the results on job mobility in the month individuals turn 65.
The impact of national vaccination policy changes on influenza incidence in the Netherlands
Authors: McDonald Scott A. , van Asten Liselotte , van der Hoek Wim , Donker Gé A. , Wallinga Jacco
Published: December 2015

Background

We assessed the impact of two major modifications of the Dutch National Influenza Prevention Programme – the introduction in 1997 of free‐of‐charge vaccination to persons aged ≥65 years and to high‐risk groups (previously only advised, and not free of charge), and the lowering of the eligible age to 60 years in 2008 – on the estimated incidence of influenza infection leading to influenza‐like illness (ILI).

Methods

Additive negative‐binomial segmented regression models were fitted to ILI data from GP sentinel surveillance in two‐eight‐season intervals (1993/4 to 2000/1, 2004/5 to 2011/12, comparing pre‐ and post‐policy‐change periods within each interval), with laboratory virological reporting of samples positive for influenza or other ILI‐causing pathogens as covariates.

Results

For the 2008 policy change, there was a significant step decrease in influenza contribution considering all ages (=−111 per 100 positives; 95% CI: −162, −65·0), <60 years and 60–64 years age groups (B = −92·1 per 100; 95% CI: −134, −55·5; B = −5·2; 95% CI: −10·3, −1·2, respectively). There was no evidence for a decrease associated with the 1997 policy change targeting the ≥65 years age group.

Conclusions

In the Netherlands, a 56% reduction in influenza contribution was associated with the 2008 policy targeting 60–64 year‐olds, but there was no effect of the earlier policy targeting ≥65‐year‐olds, for whom vaccination coverage was already rising before the policy change.