bluuebunny/crossref_metadata_2025 huggingface dataset:
CAZyme content of Pochonia chlamydosporia reflects that chitin and chitosan modification are involved in nematode parasitism
Authors: Aranda‐Martinez Almudena , Lenfant Nicolas , Escudero Nuria , Zavala‐Gonzalez Ernesto A. , Henrissat Bernard , Lopez‐Llorca Luis V.
Published: September 2016

Pochonia chlamydosporia is a soil fungus with a multitrophic lifestyle combining endophytic and saprophytic behaviors, in addition to a nematophagous activity directed against eggs of root‐knot and other plant parasitic nematodes. The carbohydrate‐active enzymes encoded by the genome of P. chlamydosporia suggest that the endophytic and saprophytic lifestyles make use of a plant cell wall polysaccharide degradation machinery that can target cellulose, xylan and, to a lesser extent, pectin. This enzymatic machinery is completed by a chitin breakdown system that involves not only chitinases, but also chitin deacetylases and a large number of chitosanases. P. chlamydosporia can degrade and grow on chitin and is particularly efficient on chitosan. The relevance of chitosan breakdown during nematode egg infection is supported by the immunolocalization of chitosan in Meloidogyne javanica eggs infected by P. chlamydosporia and by the fact that the fungus expresses chitosanase and chitin deacetylase genes during egg infection. This suggests that these enzymes are important for the nematophagous activity of the fungus and they are targets for improving the capabilities of P. chlamydosporia as a biocontrol agent in agriculture.
Asymmetric Dominance and Its Impact on Mortgage Default Deficiency Collection Efforts
Authors: Seiler Michael J.
Published: September 2016

The surge in mortgage default rates during the financial crisis has led to a corresponding dramatic increase in the type and number of firms who are entering the deficiency collection space. As such, we study the methods by which hedge funds and private equity collection firms can more profitably unwind this toxic debt. Specifically, we employ the theory of Asymmetric Dominance and find support that introducing a similar payment amount (i.e., a “decoy”) significantly induces borrowers to change their preference from one that is optimal for them to one that is suboptimal. We then employ the Left‐Most Digit effect in a new manner and demonstrate a statistically significant ability to mitigate the Asymmetric Dominance effect. Finally, we empirically find that Caucasians, males, and those of a greater net worth are more adept at avoiding violating the Independence of Irrelevant Alternatives axiom.
The Evolution and Versatility of Microalgal Biotechnology: A Review
Authors: Hamed Imen
Published: September 2016

Microalgal biotechnology has emerged due to the health‐promoting properties of microalgae related to their bioactive compounds and the great diversity of products that can be developed from algal biomass. Microalgal biomasses have been produced industrially for applications in different fields such as food, pharmaceutical, nutraceutical, cosmetic, and animal feed industries. They can be cultivated either in open systems or in closed systems (photobioreactors). Another important area is the use of microalgal biomass for energy production. It has become obvious that petroleum‐derived fuels are unsustainable, due to depleting world reserves and greenhouse gas emissions. Microalgae can provide several different types of renewable biofuels. These include methane produced by anaerobic digestion of the algal biomass, biodiesel derived from trans‐esterification of microalgal lipids, bioethanol produced from carbohydrate fermentations, and photobiologically produced biohydrogen. The idea of using microalgae as a source of fuel is not new. However, it is now being taken seriously because of increases in petroleum prices and, more significantly, the increasing concern about global warming as associated with burning fossil fuels. This review offers an update on information about microalgae, specifically emphasizing their biotechnological importance.
Pairing Modern and Paleolimnological Approaches to Evaluate the Nutrient Status of Lakes in Upper Midwest National Parks
Authors: VanderMeulen David D. , Moraska Lafrancois Brenda , Edlund Mark B. , Ramstack Hobbs Joy M. , Damstra Richard
Published: September 2016

Understanding what constitutes a reference (background) nutrient condition for lakes is important for National Park Service managers responsible for preserving and protecting aquatic resources. For this study we characterize water quality conditions in 29 lakes across four national parks, and compare their nutrient status to U.S. Environmental Protection Agency (USEPA) nutrient reference criteria and alternative criteria recently proposed by others. Where appropriate we also compare the nutrient status of these 29 lakes to state or tribal nutrient reference criteria or standards. For lakes that exceed reference criteria we investigate physical and chemical patterns, and for a subset of lakes compare modern nutrient conditions to paleolimnological (i.e., diatom‐inferred [DI]) nutrient reconstructions. Many lakes exceeded USEPA nutrient reference criteria, but met alternative less restrictive criteria. Modern nutrient conditions were also largely consistent with DI historic (pre‐1900) nutrient conditions. Lakes exceeding alternative nutrient criteria and with elevated nutrient levels relative to DI historic conditions were mostly small, shallow, and dystrophic; continued attention to their nutrient dynamics and biological response is warranted. Coupling modern and paleolimnological data offer an innovative and scientifically defensible approach to understand long‐term nutrient trends and provide greater context for comparison with reference conditions.
DNA barcodes of the native ray‐finned fishes in Taiwan
Authors: Chang Chia‐Hao , Shao Kwang‐Tsao , Lin Han‐Yang , Chiu Yung‐Chieh , Lee Mao‐Ying , Liu Shih‐Hui , Lin Pai‐Lei
Published: September 2016

Species identification based on the DNA sequence of a fragment of the cytochrome c oxidase subunit I gene in the mitochondrial genome, DNA barcoding, is widely applied to assist in sustainable exploitation of fish resources and the protection of fish biodiversity. The aim of this study was to establish a reliable barcoding reference database of the native ray‐finned fishes in Taiwan. A total of 2993 individuals, belonging to 1245 species within 637 genera, 184 families and 29 orders of ray‐finned fishes and representing approximately 40% of the recorded ray‐finned fishes in Taiwan, were PCR amplified at the barcode region and bidirectionally sequenced. The mean length of the 2993 barcodes is 549 bp. Mean congeneric K2P distance (15.24%) is approximately 10‐fold higher than the mean conspecific one (1.51%), but approximately 1.4‐fold less than the mean genetic distance between families (20.80%). The Barcode Index Number (BIN) discordance report shows that 2993 specimens represent 1275 BINs and, among them, 86 BINs are singletons, 570 BINs are taxonomically concordant, and the other 619 BINs are taxonomically discordant. Barcode gap analysis also revealed that more than 90% of the collected fishes in this study can be discriminated by DNA barcoding. Overall, the barcoding reference database established by this study reveals the need for taxonomic revisions and voucher specimen rechecks, in addition to assisting in the management of Taiwan's fish resources and diversity.
Genomic distribution and estimation of nucleotide diversity in natural populations: perspectives from the collared flycatcher (Ficedula albicollis) genome
Authors: Dutoit Ludovic , Burri Reto , Nater Alexander , Mugal Carina F. , Ellegren Hans
Published: September 2016

Properly estimating genetic diversity in populations of nonmodel species requires a basic understanding of how diversity is distributed across the genome and among individuals. To this end, we analysed whole‐genome resequencing data from 20 collared flycatchers (genome size ≈1.1 Gb; 10.13 million single nucleotide polymorphisms detected). Genomewide nucleotide diversity was almost identical among individuals (mean = 0.00394, range = 0.00384–0.00401), but diversity levels varied extensively across the genome (95% confidence interval for 200‐kb windows = 0.0013–0.0053). Diversity was related to selective constraint such that in comparison with intergenic DNA, diversity at fourfold degenerate sites was reduced to 85%, 3′ UTRs to 82%, 5′ UTRs to 70% and nondegenerate sites to 12%. There was a strong positive correlation between diversity and chromosome size, probably driven by a higher density of targets for selection on smaller chromosomes increasing the diversity‐reducing effect of linked selection. Simulations exploring the ability of sequence data from a small number of genetic markers to capture the observed diversity clearly demonstrated that diversity estimation from finite sampling of such data is bound to be associated with large confidence intervals. Nevertheless, we show that precision in diversity estimation in large outbred population benefits from increasing the number of loci rather than the number of individuals. Simulations mimicking RAD sequencing showed that this approach gives accurate estimates of genomewide diversity. Based on the patterns of observed diversity and the performed simulations, we provide broad recommendations for how genetic diversity should be estimated in natural populations.
Gendered Ageism in Australia: Changing Perceptions of Age Discrimination among Older Men and Women
Authors: McGann Michael , Ong Rachel , Bowman Dina , Duncan Alan , Kimberley Helen , Biggs Simon
Published: September 2016

This paper investigates how age and gender interact to shape older jobseekers’ experiences of age discrimination within a mixed methods framework. The analysis reveals that there has been a considerable decline in national levels of perceived ageism generally among older men relative to older women. These research findings suggest that the nature of ageism experienced by older women is qualitatively different from men. Currently, one‐size‐fits‐all, business case approaches rely on an overly narrow concept that obscures the gender and occupational dimensions of ageism. Hence, policy responses to ageism need to be far more tailored in their approach.
FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence
Authors: Spagnolo Primavera A. , Ramchandani Vijay A. , Schwandt Melanie L. , Kwako Laura E. , George David T. , Mayo Leah M. , Hillard Cecilia J. , Heilig Markus
Published: September 2016

Background

A common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses.

Methods

Forty‐nine patients with PTSD and AD were admitted for 4 weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity.

Results

FAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2‐arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain.

Conclusions

This is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics.
Exploration of Core Symptoms for the Diagnosis of Alcohol Dependence in the ICD‐10
Authors: Yoshimura Atsushi , Komoto Yasunobu , Higuchi Susumu
Published: September 2016

Background

The classification of alcohol use disorder has changed over the past century. Now, the conceptualization of alcohol dependence is still controversial. Accumulating evidence has shown the reliability and validity for the diagnosis of alcohol dependence in the ICD‐10 and DSM‐IV. However, the meaning and association of the respective diagnostic items, which are descriptive of representative symptoms, have hardly been examined. The core symptom of substance use disorder has been debated in various situations, but has never been elucidated logically.

Methods

We consecutively registered 192 patients with alcohol‐related problems who visited our hospital for the first time during a certain period. The relations and principal components among the checked items of the ICD‐10 diagnostic criteria were examined statistically.

Results

Three diagnostic items in the ICD‐10 were strongly correlated with each other and were thought to form the core symptoms of alcohol dependence: “strong desire,” “difficulties in controlling,” and “neglect of pleasures.” One major physical phenomenon, “withdrawal,” seemed to complement the core symptoms in the diagnosis of alcohol dependence. Another physical phenomenon, “tolerance,” was demonstrated to be a relatively independent item. The principal component analysis also demonstrated that the diagnostic item “difficulties in controlling” had the maximum component loading value, followed by 2 items, “neglect of pleasures” and “strong desire.”

Conclusions

The core symptomatic elements in the diagnosis of alcohol dependence were statistically suggested in this study. Knowledge of the relations and components among the diagnostic items of alcohol dependence might also be applicable to other forms of substance use dependence and behavioral addiction.
Acetaldehyde Disrupts Interferon Alpha Signaling in Hepatitis C Virus‐Infected Liver Cells by Up‐Regulating USP18
Authors: Ganesan Murali , Poluektova Larisa Y. , Tuma Dean J. , Kharbanda Kusum K. , Osna Natalia A.
Published: September 2016

Background

Alcohol consumption exacerbates the pathogenesis of hepatitis C virus (HCV) infection and worsens disease outcomes. The exact reasons are not clear yet, but they might be partially attributed to the ability of alcohol to further suppress the innate immunity. Innate immunity is known to be already decreased by HCV in liver cells.

Methods

In this study, we aimed to explore the mechanisms of how alcohol metabolism dysregulates IFNα signaling (STAT1 phosphorylation) in HCV+ hepatoma cells. To this end, CYP2E1+ Huh7.5 cells were infected with HCV and exposed to the acetaldehyde (Ach) generating system (AGS).

Results

Continuously produced Ach suppressed IFNα‐induced STAT1 phosphorylation, but increased the level of a protease, USP18 (both measured by Western blot), which interferes with IFNα signaling. Induction of USP18 by Ach was confirmed in primary human hepatocyte cultures and in livers of ethanol‐fed HCV transgenic mice. Silencing of USP18 by specific siRNA attenuated the pSTAT1 suppression by Ach. The mechanism by which Ach down‐regulates pSTAT1 is related to an enhanced interaction between IFNαR2 and USP18 that finally dysregulates the cross talk between the IFN receptor on the cell surface and STAT1. Furthermore, Ach decreases ISGylation of STAT1 (protein conjugation of a small ubiquitin‐like modifier, ISG15, Western blot), which preserves STAT1 activation. Suppressed ISGylation leads to an increase in STAT1 K48 polyubiquitination which allows pSTAT1 degrading by proteasome.

Conclusions

We conclude that Ach disrupts IFNα‐induced STAT1 phosphorylation by the up‐regulation of USP18 to block the innate immunity protection in HCV‐infected liver cells, thereby contributing to HCV‐alcohol pathogenesis. This, in part, may explain the mechanism of HCV‐infection exacerbation/progression in alcohol‐abusing patients.
Acute effects of resistance exercise on affect, arousal, and urge to drink in temporarily abstinent young adult hazardous drinkers
Authors: Ciccolo Joseph T. , Whitworth James W. , Dunsiger Shira I. , SantaBarbara Nicholas J. , Nosrat Sanaz , LaBrec Jordan E.
Published: September 2016

Background and Objective

Young adults frequently engage in hazardous alcohol consumption, and many meet the diagnostic criteria for an alcohol use disorder. The urge to drink is a defining symptom of alcohol dependence, and it is closely tied to and exacerbated by negative affect. This study examined the acute effect of resistance exercise on affect, arousal, and drinking urges in young adult (ages 21–40) hazardous drinkers.

Methods

On two separate occasions, 14 participants underwent an 18‐hour alcohol abstinence before completing, in a counter‐balanced manner, a 20‐minute session of resistance exercise and a 20‐minute video control.

Results

Significant improvements in affect (t = 2.07, p = .04) and arousal (t = 4.09, p < .01), but not urge to drink, were found with exercise.

Conclusion

Single sessions of resistance exercise can positively alter affect and arousal during alcohol abstinence.

Scientific Significance

Practical exercise interventions designed to alter affect and arousal could potentially alter drinking. (Am J Addict 2016;25:623–627)
Prospects of electrochemical immunosensors for early diagnosis of preeclampsia
Authors: Suman Pankaj , Gandhi Sonu , Kumar Prabhanshu , Garg Kirti
Published: September 2016

Preeclampsia is a vascular multisystem disorder that accounts for varying degree of morbidity and mortality of mother and the fetus. This can be significantly averted if diagnosed at an early (18‐20 weeks) stage of gestation, as there is no known way to prevent preeclampsia. In spite of extensive work on biomarker discovery, the existing method for its detection is mostly based on colorimetric immunoassays whose sensitivity is ranging in nanomolar range. Further, it has also been observed that change in the expression of a single biomarker is not sufficient to diagnose this condition. So, for early diagnosis (by 18‐20 weeks), an immuno‐diagnostic platform with detection limits in picomolar range and beyond along with the ability to do simultaneous detection of multiple analyte would be of great importance. A nano‐immunosensors with an electrochemical readout system can be a potential alternative that promises for the ultrasensitive detection of analyte with high specificity as well as suitability for on‐site analysis. Coupling the lateral flow technology with immunosensors would make it feasible to detect more than one biomarker simultaneously on a microchip. This review intends to summarize the potential preeclampsia biomarkers, limitations of existing diagnostic methods along with the recent advancements, and prospects to develop electrochemical immunosensors for early clinical diagnosis.
A prospective, cohort evaluation of major and minor airway management complications during routine anaesthetic care at an academic medical centre
Authors: Huitink J. M. , Lie P. P. , Heideman I. , Jansma E. P. , Greif R. , van Schagen N. , Schauer A.
Published: September 2016

The aim of this study was to develop an audit tool to identify prospectively all peri‐operative adverse events during airway management in a cost‐effective and reproducible way. All patients at VU University Medical Center who required general anaesthesia for elective and emergency surgical procedures were included during a period of 8 weeks. Daily questionnaires and interviews were taken from anaesthesia trainees and anaesthetic department staff members. A total of 2803 patients underwent general anaesthesia, 1384 men and 1419 women, including 2232 elective patients and 571 emergency procedures, 697 paediatric and 2106 adult surgical procedures. A total of 168 airway‐related events were reported. The incidence of severe airway management‐related events was 24/2803 (0.86%). There were 12 (0.42%) unanticipated ICU admissions, two patients (0.07%) required a surgical airway. There was one (0.04%) death, one cannot intubate cannot oxygenate (0.04%), one aspiration (0.04%) and eight (0.29%) severe desaturations < SpO2 50%. We suggest that our method to determine and investigate airway management‐related adverse events could be adopted by other hospitals.
Microvascular reactivity and endothelial glycocalyx degradation when administering hydroxyethyl starch or crystalloid during off‐pump coronary artery bypass graft surgery: a randomised trial
Authors: Kim T. K. , Nam K. , Cho Y. J. , Min J. J. , Hong Y. J. , Park K. U. , Hong D. M. , Jeon Y.
Published: September 2016

The infusion of fluids to patients may affect tissue microcirculation and the endothelial glycocalyx. However, the effects of hydroxyethyl starch and crystalloid on endothelial glycocalyx degradation and microvascular reactivity have not been evaluated in detail. We hypothesised that hydroxyethyl starch may cause less endothelial glycocalyx degradation and better microvascular reactivity than that caused by crystalloid. We randomly allocated 120 patients undergoing off‐pump coronary artery bypass graft surgery to receive up to 20 ml.kg−1 of either hydroxyethyl starch 670/0.75 or crystalloid for intra‐operative fluid resuscitation. Crystalloid was then infused to meet ongoing fluid requirements. During the peri‐operative period, vascular occlusion tests were performed to assess microvascular reactivity, and serum syndecan‐1 was measured as an index of endothelial glycocalyx degradation. The median (IQR [range]) fluid infused during surgery was significantly less in the hydroxyethyl starch group than the crystalloid group; 2800 (2150–3550 [1400–7300]) vs. 3925 (3100–4725 [1900–6700]) ml, respectively, p < 0.001. Vascular occlusion test parameters, including tissue oxygen saturation, occlusion and recovery slope did not differ significantly between the groups. Peri‐operative changes in syndecan‐1 were not significantly different between the groups. We conclude that, in patients undergoing off‐pump coronary artery bypass graft surgery, compared with crystalloid, the use of hydroxyethyl starch 670/0.75 did not result in significant differences in microvascular reactivity or endothelial glycocalyx degradation.
Intelligence quotient scores at the age of 6 years in children anaesthetised before the age of 5 years
Authors: de Heer I. J. , Tiemeier H. , Hoeks S. E. , Weber F.
Published: September 2016

We analysed the association of independent variables with non‐verbal cognition at 6 years in children with complete data (3441 from a cohort of 9901), of whom 415 were anaesthetised before the age of 5 years. Using multivariable regression, cognition was reduced by a mean (95% CI) score for children: anaesthetised before the age of 5 years, 2.1 (0.7–3.5), p = 0.004; born prematurely, 9.8 (4.1–15.4), p = 0.001; whose mothers smoked while pregnant, 2.3 (0.8–3.8), p = 0.004; whose mothers had lower IQ scores, 0.3 (0.2–0.3) for each unit reduction in maternal IQ, p < 0.0001. The association of child IQ with exposure to anaesthetic drugs was sensitive to missing data.
Pilot study demonstrates that salivary oxytocin can be measured unobtrusively in preterm infants
Authors: Kommers DR , Broeren MAC , Andriessen P , Oei SG , Feijs L , Bambang Oetomo S
Published: September 2016

Aim

This study assessed the feasibility and obtrusiveness of measuring salivary oxytocin in preterm infants receiving Kangaroo care, because this is a period of maximal bonding or co‐regulation. We also analysed possible influential determinants, including maternal oxytocin.

Methods

The saliva of preterm infants and their mothers was collected prior to, and during, Kangaroo care using cotton swabs and pooled into vials until sufficient volumes were obtained to measure oxytocin levels using a radioimmunoassay. The obtrusiveness of the infants’ collections was measured with a Likert scale.

Results

Saliva was collected unobtrusively prior to, and during, 30 Kangaroo care sessions in 21 preterm infants. This resulted in three vials with sufficient volumes of before‐Kangaroo care saliva and three with during‐Kangaroo care saliva. Oxytocin was detectable in all six vials. The Kangaroo care duration and the intensity of the mother–infant interaction before and during Kangaroo care seemed to be the most important determinants, and these should preferably be standardised in any future trials.

Conclusion

Oxytocin was measured unobtrusively in the pooled saliva of preterm infants both before and during Kangaroo care and could therefore be investigated as a biomarker in future studies.
Successful laparoscopic ligation for massive chylous ascites after rectal cancer surgery
Authors: Fukui Yudai , Shindoh Junichi , Matoba Shuichiro , Tomizawa Kenji , Hanaoka Yutaka , Toda Shigeo , Moriyama Jin , Kuroyanagi Hiroya
Published: September 2016

A 53‐year‐old man was readmitted with abdominal distention 2 weeks after undergoing laparoscopic low anterior resection with para‐aortic lymphadenectomy for advanced rectal cancer (T4aN1M0, Stage IIIb). Ultrasound revealed massive ascites, and paracentesis revealed chylous fluid with a markedly elevated triglyceride level (1762 mg/dL). Despite conservative management, the fistula remained on postoperative day 120. On percutaneous lymphangiography, the chylous leakage point was clearly visualized at the para‐aortic site, and surgical intervention was planned. The abdominal cavity was carefully explored with laparoscopy, and the lymphatic leakage point was detected at the site of previous lymphadenectomy. Leakage was stopped with direct suture ligation and fibrin glue, and the patient was discharged 2 weeks later with no recurrence of the chylous fistula. Surgical intervention can be effective in select patients with a major chylous fistula that persists despite conservative therapy. When the leakage point is localized and detectable on percutaneous lymphangiography, the laparoscopic approach may be feasible.
What Justifies a Future with Humans in It?
Authors: Murphy Timothy F.
Published: September 2016

Antinatalist commentators recommend that humanity bring itself to a close, on the theory that pain and suffering override the value of any possible life. Other commentators do not require the voluntary extinction of human beings, but they defend that outcome if people were to choose against having children. Against such views, Richard Kraut has defended a general moral obligation to people the future with human beings until the workings of the universe render such efforts impossible. Kraut advances this view on the grounds that we are obliged to exercise beneficence toward others and on the grounds that the goods available in human lives are morally compelling. This account ultimately succeeds in making no more than a prima facie defense of human perpetuation because considerations of beneficence could override – in some cases probably should – override any duty to perpetuate human beings. While the goods of human life may be distinctive, they cannot serve as reason‐giving in regard to their own perpetuation. Ironically, the exercise of beneficence may authorize the extinction of human beings, if it becomes possible to enhance the goods available to human descendants in a way that moves them away from human nature as now given. The defense of a morally obligatory and strictly human future remains elusive, even as it becomes morally desirable to work against Fateful Catastrophes, those human‐caused events that threaten to extinguish existing lives already good and enriching for their bearers.
A Bayesian Integrative Approach for Multi-Platform Genomic Data: A Kidney Cancer Case Study
Authors: Chekouo Thierry , Stingo Francesco C. , Doecke James D. , Do Kim-Anh
Published: September 2016

Integration of genomic data from multiple platforms has the capability to increase precision, accuracy, and statistical power in the identification of prognostic biomarkers. A fundamental problem faced in many multi-platform studies is unbalanced sample sizes due to the inability to obtain measurements from all the platforms for all the patients in the study. We have developed a novel Bayesian approach that integrates multi-regression models to identify a small set of biomarkers that can accurately predict time-to-event outcomes. This method fully exploits the amount of available information across platforms and does not exclude any of the subjects from the analysis. Through simulations, we demonstrate the utility of our method and compare its performance to that of methods that do not borrow information across regression models. Motivated by The Cancer Genome Atlas kidney renal cell carcinoma dataset, our methodology provides novel insights missed by non-integrative models.
Testing Violations of the Exponential Assumption in Cancer Clinical Trials with Survival Endpoints
Authors: Han Gang , Schell Michael J. , Zhang Heping , Zelterman Daniel , Pusztai Lajos , Adelson Kerin , Hatzis Christos
Published: September 2016

Personalized cancer therapy requires clinical trials with smaller sample sizes compared to trials involving unselected populations that have not been divided into biomarker subgroups. The use of exponential survival modeling for survival endpoints has the potential of gaining 35% efficiency or saving 28% required sample size (Miller, 1983), making personalized therapy trials more feasible. However, the use of exponential survival has not been fully accepted in cancer research practice due to uncertainty about whether or not the exponential assumption holds. We propose a test for identifying violations of the exponential assumption using a reduced piecewise exponential approach. Compared with an alternative goodness-of-fit test, which suffers from inflation of type I error rate under various censoring mechanisms, the proposed test maintains the correct type I error rate. We conduct power analysis using simulated data based on different types of cancer survival distribution in the SEER registry database, and demonstrate the implementation of this approach in existing cancer clinical trials.
Rethinking the role of critique in physical geography
Authors: Tadaki Marc
Published: September 2016

Key Messages

The relationships between environmental scientists and society can be usefully conceptualized through the lens of critique.

Three modes of critique are distinguished, each drawing attention to different practices and outcomes in environmental science.

Physical geographers can and should embrace multiple and normative concepts of critique through their work.
The integration of Human and Physical Geography revisited
Authors: Goudie Andrew S.
Published: September 2016

Key Messages

There are increasing signs of potential integration within Geography.

A range of areas for collaboration exists between Human and Physical Geographers.

Geography is not irredeemably divided.
Studying Organizational Creativity as Process: Fluidity or Duality?
Authors: Fortwengel Johann , Schüßler Elke , Sydow Jörg
Published: September 2016

This paper contributes to process studies on organizational creativity by developing two competing research agendas. The first perspective, the ‘becoming’ view, depicts creativity as a constant flow of activity that crystallizes every once in a while in unpredictable moments of creativity. The second perspective, the ‘practice’ view, understands creativity as a practised social process, in which structures play the important role of both enabling and constraining individual agents in pursuing creativity as a collective phenomenon. We compare and contrast these two theoretical perspectives, which are based on different process ontologies, and discuss their methodological implications. We argue that the practice perspective offers particular promise, because it allows us to address the important yet paradoxical question of how creativity may be organized and managed.
Structure–activity relationship of caffeic acid phenethyl ester analogs as new 5‐lipoxygenase inhibitors
Authors: Doiron Jérémie A. , Leblanc Luc M. , Hébert Martin J. G. , Levesque Natalie A. , Paré Aurélie F. , Jean‐François Jacques , Cormier Marc , Surette Marc E. , Touaibia Mohamed
Published: September 2016

Leukotrienes (LTs) are a class of lipid mediators implicated in numerous inflammatory disorders. Caffeic acid phenethyl ester (CAPE) possesses potent anti‐LTs activity through the inhibition of 5‐lipoxygenase (5‐LO), the key enzyme in the biosynthesis of LTs. In this study, we describe the design and synthesis of CAPE analogs as radical scavengers and 5‐LO inhibitors. Caffeic esters bearing propargyl and allyl linkers between the caffeoyl and aryl moieties (4a–i and 5a–i, respectively) were synthesized by Sonogashira and Heck cross‐coupling reactions to probe the effects of flexibility and aryl substitution on 5‐LO inhibition. Caffeoyl alcohol and ethers (6, 7a–b) as well as caffeoyl aldehyde and ketones (8a–e) were synthesized to elucidate the importance of the ester linkage for inhibitory activity. All tested compounds proved to be good radical scavengers (IC50 of 10–30 μm). After preliminary anti‐LTs activity screening in HEK293 cell models, 5‐LO inhibition potential of selected compounds was determined in human polymorphonuclear leukocytes (PMNL). Most screened compounds outperformed CAPE 3 in concentration‐dependent assays on PMNL, with ester dimers 4i and 5i along with caffeoyl ethers 7a–b being roughly eight‐, seven‐, and 16‐fold more potent than Zileuton, with IC50 values of 0.36, 0.43, and 0.18 μm, respectively.
Physical fitness in preschool children: association with sex, age and weight status
Authors: Latorre Román P. Á. , Moreno del Castillo R. , Lucena Zurita M. , Salas Sánchez J. , García‐Pinillos F. , Mora López D.
Published: September 2016

Background

Because fitness level is a potent biomarker of health from an early age, the improvements of physical fitness performance through the promotion of physical activity could be important for the health of preschool children, particularly in obesity prevention.

Objective

The purpose of this study is to determine the physical fitness in children aged 3–6 years, discriminating performance by sex, age and body mass index (BMI).

Method

A total of 3868 children from 3 to 6 years agreed voluntarily to participate. Demographic characteristics revealed that 1961 children were male (age: 55.71 ± 11.11 months old, BMI = 16.03 ± 1.93 kg/m2), and 1907 were female (age 56.16 ± 0.97 months old, BMI = 15.85 ± 1.89 kg/m2), and they were selected from 51 schools in southern Spain.

Results

Significant differences were found between sexes: boys showed a greater performance on cardio respiratory endurance, reaction time, strength and running speed. We found significant differences by sex in the different age groups (3, 4, 5 and 6 years old).

Conclusions

Sex differences in physical fitness are evident at an early age; in addition, the relationship between physical fitness and BMI is inconsistent in preschool children. The improvements of physical fitness performance and its association with physical activity could be important for the health of children, particularly in obesity prevention.
Birth and Adoptive Parent Antisocial Behavior and Parenting: A Study of Evocative Gene–Environment Correlation
Authors: Klahr Ashlea M. , Burt S. Alexandra , Leve Leslie D. , Shaw Daniel S. , Ganiban Jody M. , Reiss David , Neiderhiser Jenae M.
Published: September 2016

Negative parenting is shaped by the genetically influenced characteristics of children (via evocative rGE) and by parental antisocial behavior; however, it is unclear how these factors jointly impact parenting. This study examined the effects of birth parent and adoptive parent antisocial behavior on negative parenting. Participants included 546 families within a prospective adoption study. Adoptive parent antisocial behavior emerged as a small but significant predictor of negative parenting at 18 months and of change in parenting from 18 to 27 months. Birth parent antisocial behavior predicted change in adoptive father's (but not mother's) parenting over time. These findings highlight the role of parent characteristics and suggest that evocative rGE effects on parenting may be small in magnitude in early childhood.
Implant Stability Quotients of Osteotome Bone Expansion and Conventional Drilling Technique for 4.1 mm Diameter Implant at Posterior Mandible
Authors: Hong Hsiang‐Hsi , Hong Adrienne , Yang Lan‐Yan , Chang Wei‐Yang , Huang Yi‐Fang , Lin Yen‐Ting
Published: September 2016

Background

Clinical conclusions in studying the stability and osseointegration of mandibular implants positioned using the bone expansion techniques are conflicting and limited.

Purpose

The objective was to examine the implant stability quotient (ISQ) values of mandibular posterior dental implants with 4.1 mm diameter that inserted with osteotome bone expansion technique versus conventional drilling technique during a 12‐week observation period.

Materials and Methods

Twenty‐four implants with 4.1mm diameter in 18 patients were included. Twelve implants in 10 patients were positioned using osteotome bone expansion technique, and 12 fixtures in 9 patients were installed using the conventional drilling technique. The ISQ values of a 3.3 mm diameter implant was measured at recipient sites (ISQb) before final drilling or expansion technique to standardize the increased ISQ value of 4.1 mm diameter implants. The ISQ values at Weeks 0, 1, 2, 3, 4, 6, 8, 10, and 12 post‐surgery were recorded. Data were analyzed by Wilcoxon rank sum test, repeated measure ANOVA, and Fisher Lest Significant Difference test.

Results

Calibrated according to a 3.3‐mm‐diameter implant, bone expansion technique was adopted for the sites with ISQ≦65 bone density, and the areas with ISQ >65 bone condition were treated with conventional drilling technique (p =.038). Both groups presented a similar healing pattern and a comparable ISQ reading from Week 0 to Week 12 (p > .05) for 4.1 mm diameter implants. However, bone expansion technique could enhance more stability when the ISQ values were calibrated by 3.3 mm diameter implant (p < .05).

Conclusions

Bone expansion technique substantially increased more ISQ values from primary stability and achieved comparable primary and secondary stabilities with the conventional technique. Both groups reached a stability plateaus at Week 10.
Exploring Cognitive Relations Between Prediction in Language and Music
Authors: Patel Aniruddh D. , Morgan Emily
Published: September 2016

The online processing of both music and language involves making predictions about upcoming material, but the relationship between prediction in these two domains is not well understood. Electrophysiological methods for studying individual differences in prediction in language processing have opened the door to new questions. Specifically, we ask whether individuals with musical training predict upcoming linguistic material more strongly and/or more accurately than non‐musicians. We propose two reasons why prediction in these two domains might be linked: (a) Musicians may have greater verbal short‐term/working memory; (b) music may specifically reward predictions based on hierarchical structure. We provide suggestions as to how to expand upon recent work on individual differences in language processing to test these hypotheses.
The Pursuit of Word Meanings
Authors: Stevens Jon Scott , Gleitman Lila R. , Trueswell John C. , Yang Charles
Published: September 2016

We evaluate here the performance of four models of cross‐situational word learning: two global models, which extract and retain multiple referential alternatives from each word occurrence; and two local models, which extract just a single referent from each occurrence. One of these local models, dubbedPursuit, uses an associative learning mechanism to estimate word‐referent probability but pursues and tests the best referent‐meaning at any given time.Pursuitis found to perform as well as global models under many conditions extracted from naturalistic corpora of parent‐child interactions, even though the model maintains far less information than global models. Moreover,Pursuitis found to best capture human experimental findings from several relevant cross‐situational word‐learning experiments, including those of Yu and Smith (), the paradigm example of a finding believed to support fully global cross‐situational models. Implications and limitations of these results are discussed, most notably that the model characterizes only the earliest stages of word learning, when reliance on the co‐occurring referent world is at its greatest.
Effect of GLP‐1 receptor agonist treatment on body weight in obese antipsychotic‐treated patients with schizophrenia: a randomized, placebo‐controlled trial
Authors: Ishøy Pelle L. , Knop Filip K. , Broberg Brian V. , Bak Nikolaj , Andersen Ulrik B. , Jørgensen Niklas R. , Holst Jens J. , Glenthøj Birte Y. , Ebdrup Bjørn H.
Published: September 2016

Aims

Schizophrenia is associated with cardiovascular co‐morbidity and a reduced life‐expectancy of up to 20 years. Antipsychotics are dopamine D2
receptor antagonists and are the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects such as obesity and diabetes. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP‐1RA, exenatide once‐weekly, in non‐diabetic, antipsychotic‐treated, obese patients with schizophrenia.

Material and methods

Antipsychotic‐treated, obese, non‐diabetic, schizophrenia spectrum patients were randomized to double‐blinded adjunctive treatment with once‐weekly subcutaneous exenatide (n = 23) or placebo (n = 22) injections for 3 months. The primary outcome was loss of body weight after treatment and repeated measures analysis of variance was used as statistical analysis.

Results

Between March 2013 and June 2015, 40 patients completed the trial. At baseline, mean body weight was 118.3 ± 16.0 kg in the exenatide group and 111.7 ± 18.0 kg in the placebo group, with no group differences (
P
= .23). The exenatide and placebo groups experienced significant (
P
= .004), however similar (
P
= .98), weight losses of 2.24 ± 3.3 and 2.23 ± 4.4 kg, respectively, after 3 months of treatment.

Conclusions

Treatment with exenatide once‐weekly did not promote weight loss in obese, antipsychotic‐treated patients with schizophrenia compared to placebo. Our results could suggest that the body weight‐lowering effect of GLP‐1RAs involves dopaminergic signaling, but blockade of other receptor systems may also play a role. Nevertheless, anti‐obesity regimens effective in the general population may not be readily implemented in antipsychotic‐treated patients with schizophrenia.
Exploring uses of the UK Clinical Aptitude Test‐situational judgement test in a dental student selection process
Authors: Lambe P. , Kay E. , Bristow D.
Published: September 2016

Aim

In 2013 the UKCAT included a non‐cognitive situational judgement test in addition to the four cognitive subtests commonly used by UK dental schools to select students. However, little is known about the situational judgement test's psychometric properties and relationship to other selection tools. This study's aim was explore these issues to inform decisions about the inclusion of the UKCAT SJT in the dental student selection process.

Method

The sample comprised a cohort of applicants to a Bachelor of Dental Surgery programme, at a UK dental school, which does not use achievement in the UKCAT SJT in its selection process. The impact on applicant outcomes of two theoretical uses of the UKCAT SJT was examined. First, SJT Band was used as the criterion for offers of a place instead of the school's admission interview, and second, weighted UKCAT scores, including a weighted SJT Band score, were ranked to make interview invitation decisions. Associations between SJT Band, UKCAT cognitive scores, interview score and performance in first year assessments were examined.

Results

If SJT Band 1 & 2 were used as the criterion for an offer of a place, some applicants rejected by this school's interview, including ‘red flagged’ applicants, would have received an offer of a place. Using a weighted UKCAT/SJT system for invitation for interview decisions increased the mean total UKCAT cognitive score of those invited for interview but included applicants rejected by this school's structured interview, including ‘red flagged’ applicants. Neither usage disadvantaged under‐represented groups. SJT Band correlated with UKCAT score (n = 228, rs = −0.38, P < 0.01) with interview score (n = 186, rs = −0.17, P < 0.05) but not with first year study assessments.

Conclusion

This study has shown that the UKCAT SJT does not add value to the existing methods of this dental school to make valid, reliable and fair student selection decisions.
Epidemiology of bloodstream infections in patients with myeloma receiving current era therapy
Authors: Teh Benjamin W. , Harrison Simon J. , Slavin Monica A. , Worth Leon J.
Published: September 2016

Background

Bloodstream infections (BSIs) are a significant complication of treatment for multiple myeloma (MM). The objective of this study was to define the epidemiology of BSI with current era MM treatment regimens, including immunomodulatory drugs, proteasome inhibitors and autologous haematopoietic stem cell transplantation (ASCT).

Methods

Clinical and microbiology records of patients with MM diagnosed between 2008 and 2012 were reviewed using a standardised tool to capture patient demographics, myeloma characteristics and BSI characteristics (type, severity, outcomes). Conditional risk set modelling was used to determine clinical predictors of BSI.

Results

Of 199 studied patients, 71 (35.6%) had confirmed BSI (98 infection episodes). Peak incidence was 65.1 infections/100 patient‐years at 4–6 months following MM diagnosis with a late peak at 64–66 months. Gram‐positive pathogens were responsible for the majority (54.5%) of infections during induction, whilst gram‐negative pathogens were responsible for the majority (57.7%) of infections during disease progression. Overall, Escherichia coli was the most frequently identified pathogen. Streptococcus pneumoniae comprised 6.1% of all BSIs at a median of 7.5 months following MM diagnosis. Highest rates of ICU admission (23.1%) and mortality (11.5%) were seen with BSIs in patients with progressive disease. Recent ASCT was independently associated with increased BSI risk (HR 3.09, P = 0.05).

Conclusions

Treatment of progressive disease is a high‐risk period for infection, evidenced by high proportions of BSI due to gram‐negative pathogens and S. pneumoniae. Targeted evaluation of preventative strategies (prophylaxis, vaccination) to reduce morbidity and mortality during this period is required.