bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic phenotypic stability of a bi-stable auto regulatory gene
Authors: Besya Azim-Berdy , Grönlund Andreas 
Published: March 2016

AbstractEven under homogenous conditions clonal cells can assume different distinct states for generations to follow, also known as epigenetic inheritance. Such long periods of different phenotypic states can be formed due to the existence of more than one stable state in the molecule concentration, where the different states are explored through molecular fluctuations. By formulating a single reaction variable representing the birth and death of molecules, including transcription, translation and decay, we calculate the escape time from the phenotypic states attained from autocatalytic synthesis through a Fokker- Planck formulation and integration of an effective pseudo-potential. We calculate the stability of the phenotypic states both for cooperative binding feedback and dimer binding feedback, resulting in non-linear decay.
A multimodal imaging workflow to visualize metal mixtures in the human placenta and explore colocalization with biological response markers
Authors: Niedzwiecki Megan M , Austin Christine , Remark Romain , Merad Miriam , Gnjatic Sacha , Estrada-Gutierrez Guadalupe , Espejel-Nuñez Aurora , Borboa-Olivares Hector , Guzman-Huerta Mario , Wright Rosalind J , Wright Robert O , Arora Manish 
Published: March 2016

Abstract
Fetal exposure to essential and toxic metals can influence life-long health trajectories. The placenta regulates chemical transmission from maternal circulation to the fetus and itself exhibits a complex response to environmental stressors. The placenta can thus be a useful matrix to monitor metal exposures and stress responses in utero, but strategies to explore the biologic effects of metal mixtures in this organ are not well-developed. In this proof-of-concept study, we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to measure the distributions of multiple metals in placental tissue from a low-birth-weight pregnancy, and we developed an approach to identify the components of metal mixtures that colocalized with biological response markers. Our novel workflow, which includes custom-developed software tools and algorithms for spatial outlier identification and background subtraction in multidimensional elemental image stacks, enables rapid image processing and seamless integration of data from elemental imaging and immunohistochemistry. Using quantitative spatial statistics, we identified distinct patterns of metal accumulation at sites of inflammation. Broadly, our multiplexed approach can be used to explore the mechanisms mediating complex metal exposures and biologic responses within placentae and other tissue types. Our LA-ICP-MS image processing workflow can be accessed through our interactive R Shiny application ‘shinyImaging’, which is available at https://mniedz.shinyapps.io/shinyImaging/ or through our laboratory’s website, http://labs.icahn.mssm.edu/lautenberglab/research-areas/.
Spekulation um Spionage
Authors: Pabst Inga 
Published: March 2016

Asklepios kämpft mit dem ersten Lauschangriff im Gesundheitswesen: Auch Wochen nach der Entdeckung verwanzter Telefone in der Chefetage der Hamburger Klinik-
zentrale ist unklar, wer hinter der Spionageaktion steckt.
Network synchronization in hippocampal neurons
Authors: Penn Yaron , Segal Menahem , Moses Elisha 
Published: March 2016

Significance
We show that neurons from the hippocampus and cortex fire in an oscillatory manner, both individually and as a network. When disconnected, the majority of neurons are independent intrinsic oscillators, each with its own natural frequency. Synchronization of the neurons occurs when coupling is introduced. Weak coupling already leads to convergence of all of the oscillators to one common oscillation frequency. Strikingly, this common frequency is close to the mean distribution of their natural frequencies. Strengthening the coupling decreases the phase differences of the oscillators to practically zero, leading to synchronous periodic network bursts. Overall, we show that periodic network bursts originate in collective effects rather than in specialized pacemaking elements that control the rest of the network.
Variation, individual differences and second language processing
Authors: Dyson Bronwen Patricia 
Published: March 2016

Abstract
Research on second language acquisition has located individual variation, without clarifying whether language processing prompts learners to differ systematically in the production of syntax and morphology. To address this issue, the study examined the hypothesis on variation in Processability Theory. This theory predicts that, within second language development, individual learners vary systematically in how they respond to developmental conflicts. Specifically, learners have distinct types, which are evident in their use of options and 'trailers' (structures which emerge late). Longitudinal spoken data were collected over one academic year from six adolescent ESL learners. The results revealed different learner types in terms of syntactic options and trailers. However, the learners had less clear types for the morphological options, used unpredicted options, and lacked consistency in their use of syntactic and morphological trailers. The paper suggests that learners vary in processing due to diverse orientations towards the acquisition of either syntax or morphology.
Implementation and Enforcement of Best Management Practices for Florida Ornamental Aquaculture with an Emphasis on Nonnative Species
Authors: Tuckett Quenton M , Ritch Jared L , Lawson Katelyn M , Hill Jeffrey E 
Published: March 2016

Abstract
Tropical ornamental aquaculture is dominated by the production of nonnative species and is an important industry in Florida. However, the escape of nonnative species can pose challenges to the industry and also natural resource managers. Escapement of nonnative species and their potential impacts has led to suggestions that ornamental aquaculture is unregulated and lacks transparency. Comprehensive regulation of Florida aquaculture began in 1999 with the creation of the Division of Aquaculture (Florida Department of Agriculture and Consumer Services; FDACS) along with aquaculture best management practices (BMPs). Although FDACS regulates commercial aquaculture through application of BMPs, which includes provisions for escapement of nonnative species, the implementation of aquaculture BMPs has been largely unverified. Our objective was to examine how aquaculture BMPs have been implemented to prevent the escape of nonnative species, how facilities are inspected, and the rates and causes of noncompliance. Site visits were conducted alongside FDACS inspectors on two occasions at 23 aquaculture facilities. Historical compliance records dating back to 1999 were also acquired. All facilities implemented BMPs to address escapement, which was shown by operational practices and infrastructure. The FDACS inspectors routinely enforced aquaculture BMPs, especially in areas of effluent control. When noncompliance issues were noted (57% of facilities in 2013; 39% in 2014), they were often minor (48% of issues) and quickly remedied by producers. Noncompliance with BMPs varied among facilities and was more often related to the release of sediment than nonnative species escapement. Noncompliance was also related to the size of the facility (number of ponds and greenhouses) and the presence of a detention pond. Because of its transparency, regulation of Florida aquaculture might provide a model for the development, implementation, and verification of aquaculture BMPs.
Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity*
Authors: Cohen Jeremy , Pretorius Carel J. , Ungerer Jacobus P. J. , Cardinal John , Blumenthal Antje , Presneill Jeff , Gatica-Andrades Marcela , Jarrett Paul , Lassig-Smith Melissa , Stuart Janine , Dunlop Rachel , Starr Therese , Venkatesh Bala 
Published: March 2016

Objectives:
To measure tissue glucocorticoid sensitivity in patients with septic shock and determine its relationship to standard measurements of adrenal function and of outcome.

Design:
Prospective observational trial.

Setting:
Teaching hospital ICU.

Subjects:
Forty-one patients and 20 controls were studied.

Interventions:
Glucocorticoid sensitivity was measured by in vitro suppression of cytokine production from lipopolysaccharide-stimulated leukocytes.

Measurements and Main Results:
There was no significant difference between the groups in the relative suppression of cytokine production, although there was a greater range and variance in the patient data. Patients in the lowest quartile of glucocorticoid sensitivity had higher Acute Physiology and Chronic Health Evaluation II scores (25 [24–28] vs 20 [14–23]; p = 0.02) and a trend toward higher mortality (30% vs 0%; p = 0.2) compared to those in the highest. The mRNA expression of the β variant of the glucocorticoid receptor and the 11-β hydroxysteroid dehydrogenase 2 isozyme were significantly higher in patients compared to controls (8.6-fold, p = 0.002 and 10.1-fold, p = 0.0002, respectively). Changes in mRNA expression of these genes did not correlate with measurements of glucocorticoid sensitivity.

Conclusions:
Patients with septic shock and controls do not differ in their median glucocorticoid sensitivity. However, patients exhibited a greater variability in glucocorticoid responsiveness and had evidence of association between increased sickness sensitivity and reduced glucocorticoid sensitivity. Sensitivity to glucocorticoids did not appear to be mediated by changes in the expression of the β variant of the glucocorticoid receptor or the 11-β hydroxysteroid dehydrogenase 2 isozyme.
Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial
Authors: Maiden Matthew J. , Chapman Marianne J. , Torpy David J. , Kuchel Timothy R. , Clarke Iain J. , Nash Coralie H. , Fraser Jonathan D. , Ludbrook Guy L. 
Published: March 2016

Objectives:
Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock.

Design:
Randomized blinded placebo-controlled trial.

Setting:
Preclinical research laboratory.

Subjects:
Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion.

Interventions:
Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone.

Measurements and Main Results:
Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± sd μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function.

Conclusions:
A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.
The heterogeneity of headache patients who self-medicate: a cluster analysis approach
Authors: Mehuys Els , Paemeleire Koen , Crombez Geert , Adriaens Els , Van Hees Thierry , Demarche Sophie , Christiaens Thierry , Van Bortel Luc , Van Tongelen Inge , Remon Jean-Paul , Boussery Koen 
Published: March 2016

Abstract
Patients with headache often self-treat their condition with over-the-counter analgesics. However, overuse of analgesics can cause medication-overuse headache. The present study aimed to identify subgroups of individuals with headache who self-medicate, as this could be helpful to tailor intervention strategies for prevention of medication-overuse headache. Patients (n = 1021) were recruited from 202 community pharmacies and completed a self-administered questionnaire. A hierarchical cluster analysis was used to group patients as a function of sociodemographics, pain, disability, and medication use for pain. Three patient clusters were identified. Cluster 1 (n = 498, 48.8%) consisted of relatively young individuals, and most of them suffered from migraine. They reported the least number of other pain complaints and the lowest prevalence of medication overuse (MO; 16%). Cluster 2 (n = 301, 29.5%) included older persons with mainly non-migraine headache, a low disability, and on average pain in 2 other locations. Prevalence of MO was 40%. Cluster 3 (n = 222, 21.7%) mostly consisted of patients with migraine who also report pain in many other locations. These patients reported a high disability and a severe limitation of activities. They also showed the highest rates of MO (73%).
Defining problematic pharmaceutical opioid use among people prescribed opioids for chronic noncancer pain: do different measures identify the same patients?
Authors: Campbell Gabrielle , Bruno Raimondo , Lintzeris Nicholas , Cohen Milton , Nielsen Suzanne , Hall Wayne , Larance Briony , Mattick Richard P. , Blyth Fiona , Farrell Michael , Degenhardt Louisa 
Published: March 2016

Abstract
The International Classification of Diseases (ICD) and the Diagnostic and Statistical Manual (DSM) are routinely used in diagnosing illicit substance use disorders, but for people taking prescribed opioids they remain controversial. In pain medicine, the concept of “Addiction” is preferred with reduced emphasis on tolerance and withdrawal. This article examines the prevalence and characteristics of pharmaceutical opioid dependence/disorder according to ICD, DSM, and the pain medicine concept of “Addiction,” among chronic noncancer pain (CNCP) patients prescribed opioids. In the current study, we used data from a national sample of 1134 people prescribed opioids for CNCP. Past 12-month “Addiction” (based on Pain Medicine definition), DSM, and ICD dependence definitions were assessed using the Composite International Diagnostic Interview. Twenty-four percent of the cohort met the criteria for “Addiction,” 18% for DSM-5 use disorder and 19% for ICD-11 dependence. There was “substantial” concordance between “Addiction” and both DSM-5 use disorder and ICD-11 dependence, although concordance was much greater with ICD-11 dependence (kappa = 0.63 and 0.79, respectively). Participants meeting the criteria for “Addiction” only were older, less likely to engage in nonadherent behaviours, self-reported fewer problems or concerns with their medication, and had lower rates of psychological distress than those who also met the DSM-5 and ICD-11 criteria. The definition of “Addiction” captures a larger group of patients than other classification systems and includes people with fewer “risk” behaviours. Despite removal of tolerance and withdrawal for prescribed opioid use for DSM-5, we found that “Addiction” was more closely related to an ICD-11 diagnosis of pharmaceutical opioid dependence.
Pediatric Acute‐on‐Chronic Liver Failure in a Specialized Liver Unit
Authors: Alam Seema , Lal Bikrant B. , Sood Vikrant , Rawat Dinesh 
Published: March 2016

ABSTRACTObjectives:The aim of the study was to assess the prevalence, profile, outcome, and predictive factors of pediatric acute‐on‐chronic liver failure (ACLF).Methods:All children 3 months to 18 years satisfying the Asia Pacific Association for the Study of Liver Diseases definition of ACLF were included. Data were both extracted from records (January 2011 to December 2014) and prospectively collected (January to October 2015). Successful outcome was defined as survival with native liver at 90 days, whereas poor outcome included those who died or received liver transplantation.Results:Of the 499 children with chronic liver disease (CLD), 56 (11.2%) presented as ACLF, with a mean age of 9.35 (±4.39) years. Wilson disease and autoimmune hepatitis were the commonest underlying CLDs accounting for 24 (42.8%) and 18 (32.1%) cases, respectively. The most frequent events precipitating ACLF were a flare up of the underlying disease in 27 (48.2%) and acute viral hepatitis in 17 (30%). Poor outcome occurred in 22 (39.3%) children: 17 (30.4%) died and 5 (8.9%) received liver transplantation. Poor outcome was associated with grades 3 to 4 hepatic encephalopathy, bilirubin ≥17.5, international normalized ratio ≥3.5, and presence of 2 or more organ failures. On multivariate analysis, a Chronic Liver Failure‐Sequential Organ Failure Assessment score ≥10 best predicted mortality (odds ratio 20.45, 95% confidence interval 3.9–106.7).Conclusions:ACLF is present in 11.2% of childhood CLD, with a 90‐day native liver survival of 61%. A Chronic Liver Failure‐Sequential Organ Failure Assessment score of ≥10 best predicts mortality at day 90.
Bioengineering cobalt chromium cardiovascular stent biomaterial for biofunctionalization
Authors: Jeewandara Thamarasee M. 
Published: March 2016

AbstractSuboptimal biocompatibility of cardiovascular stents manifest as non-compliance at stent-artery interfacein vivo. We optimized a plasma-activated coating (PAC) technology to modify cobalt chromium alloy L605 (PAC-L605) surface of an implantable coronary stent material, for improved biofunctionalization. The PAC-L605 surfaces displayed covalent binding capacity of a protein candidate tropoelastin (TE) by retaining 70.3% of TE after SDS detergent washing. Human coronary artery endothelial cell (HCAEC) proliferation visualized with crystal violet staining, did not vary significantly among the biomaterials at 3 or 5 days. Anchorage of cell cytoskeleton visualized with immunofluorescence and scanning electron microscopy (SEM), showed homogenous cell morphology on PAC/TE (with TE) surfaces. Surface hemocompatibility was assessed with static and flow blood assays, the hydrophilic PAC-L605 displayed lower clot formation compared to L605. Area of surface fibrinogen deposited was significantly lower on PAC-L605 vs. L605. Selected ISO 10993-4 tests for biological evaluation of medical devices in contact with blood indicated significantly lowered plasma markers of thrombin-antithrombin complex (TAT), beta-thromboglobulin (β-TG), soluble P-selectin and soluble terminal complement complex (SC5b-9) on PAC-L605 vs. L605. There was no significant difference for plasma biomarkers of polymorphonuclear elastase (PMN elastase) on PAC-L605 vs. L605. Improved surface biofunctionalization of implantable cardiovascular materials could be achieved by plasma-activated coating (PAC).
Crunch: Integrated processing and modeling of ChIP-seq data in terms of regulatory motifs
Authors: Berger Severin , Omidi Saeed , Pachkov Mikhail , Arnold Phil , Kelley Nicholas , Salatino Silvia , van Nimwegen Erik 
Published: March 2016

Although it has become routine for experimental groups to apply ChIP-seq technology to quantitatively characterize the genome-wide binding of transcription factors (TFs), computational analysis procedures remain far from standardized, making it difficult to meaningfully compare ChIP-seq results across experiments. In addition, while genome-wide binding patterns must ultimately be determined by local constellations of binding sites in the DNA, current analysis is typically limited to a standard search for enriched motifs in ChIP-seq peaks.Here we present Crunch, a completely automated computational method that performs all ChIP-seq analysis from quality control through read mapping and peak detecting, and integrates comprehensive modeling of the ChIP signal in terms of known and novel binding motifs, quantifying the contribution of each motif, and annotating which combinations of motifs explain each binding peak.Applying Crunch to 128 ChIP-seq datasets from the ENCODE project we find that TFs naturally separate into ‘solitary TFs’, for which a single motif explains the ChIP-peaks, and ‘co-binding TFs’ for which multiple motifs co-occur within peaks. Moreover, for most datasets the motifs that Crunch identifiedde novooutperform known motifs and both the set of co-binding motifs and the top motif of solitary TFs are consistent across experiments and cell lines. Crunch is implemented as a web server (crunch.unibas.ch), enabling standardized analysis of any collection of ChIP-seq datasets by simply uploading raw sequencing data. Results are provided both in a graphical interface and as downloadable files.
School leadership and management in South Africa
Authors: Bush Tony , Glover Derek 
Published: March 2016

Purpose– The purpose of this paper is to provide a systematic review of the literature on school leadership and management in South Africa, linked to the 20th anniversary of democratic government and integrated education.Design/methodology/approach– The authors conducted a systematic review of all published work since 2007 with a more selective review of sources before 2007.Findings– The findings show emerging evidence about the development of school leadership and management in South Africa but they also highlight on-going challenges, including poor learner outcomes, conflict with teacher unions, uneasy relationships between principals and school governing bodies, and leadership which remains focused on administration rather than teaching and learning.Research limitations/implications– The findings show that research on school leadership and management is developing but remains limited in terms of its scope and a reliance on small-scale unfunded projects.Practical/implications– The findings confirm the need for specialist leadership training for current and aspiring principals and for other senior and middle leaders.Social/implications– The findings show that South Africa remains a divided society with great differences in the quality of education available to learners, based on social class rather than race.Originality/value– The paper’s value lies in the comprehensive and systematic review of research on school leadership.