bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitation of Osborne Dam outlets
Authors: Tumbare Michael J. , Makwarimba Peter
Published: November 2016

Purpose

The purpose of this paper is to communicate and share experiences with other dam designers, operators and maintenance officers arising from the rehabilitation of the Osborne Dam outlets, pursuant to informing future dam outlet designs and rehabilitation of similar dam outlets.

Design/methodology/approach

This paper documents and utilizes actual events that occurred before and during the rehabilitation of the outlets. Some solutions applied were unique, with resultant innovative engineering designs being decided on site. Realizing that a descriptive research format would best serve the sharing of experiences of the outlets’ rehabilitation, the case study approach was selected. Before commencement of the rehabilitation works, the different operational problems that had been identified, photographed and documented by the dam’s operating staff were verified by the dam owner’s engineers, technicians and consultants. Visual and photographic verification was done using divers for areas under water. Literature review was conducted so as to learn from solutions employed elsewhere. A physical model of the solution considered the best way to keep the intake tower dry was made and tested.

Findings

The outlets’ rehabilitation works, taking 12 months to complete at a total cost of US$5 million, involved installation of new service gates, replacement of the sleeve valves, refurbishment of the butterfly valves and provision of dewatering pumps.

Originality/value

This paper offers unique experiences and lessons for dam designers and other dam operation and maintenance officers while contributing to the body of knowledge of outlet works rehabilitation.
On-site construction productivity in Malaysian infrastructure projects
Authors: Durdyev Serdar , Ismail Syuhaida
Published: November 2016

Purpose

The purpose of this paper is to examine the factors constraining the on-site construction productivity and measures for its improvement in Malaysian construction industry.

Design/methodology/approach

Questionnaire survey is administered to 171 respondents, comprising government authorities and construction players. A total of 39 constraints are found to be significant factors in various risk levels.

Findings

Consequently, improvement measures are recommended addressing those constraints to on-site construction productivity. It is believed that the findings of this study will assist in achieving high level of on-site construction productivity by focusing and acting upon the most risky constraints, where construction players in Malaysia could be guided well in their efforts in a time-, cost- and quality-effective manner.

Originality/value

It is believed that the findings of this study will assist in achieving high level of on-site construction productivity by focusing and acting upon the most risky constraints, where construction players in Malaysia could be guided well in their efforts in a time-, cost- and quality-effective manner.
Online Disaster Management: Applicability of the European Data Protection Framework and Its Key Principles
Authors: Jasmontaite Lina , Dimitrova Diana
Published: November 2016

The availability of applications that could be used by first responders and citizens in emergency situations has been constantly increasing over the past years. This trend is predetermined by the fact that various applications facilitate situational awareness and optimize data exchange between multiple actors. Yet the use of new technologies should be considered in the context of the applicable legal framework. Therefore, in this contribution, we discuss the applicability of the European data protection framework and its key principles related to online disaster management, and in particular, the processing of personal data when responding to disasters. The contribution provides examples of issues arising from the use of mobile apps.
BJOG Editor's Choice
Authors: Marsh Michael
Published: November 2016

Deputy Editor‐in‐Chief, Mr. Michael Marsh, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/december-editors-choice-2016.
A View to the Future: A Novel Approach for 3D–3D Superimposition and Quantification of Differences for Identification from Next‐Generation Video Surveillance Systems
Authors: Gibelli Daniele , De Angelis Danilo , Poppa Pasquale , Sforza Chiarella , Cattaneo Cristina
Published: November 2016

Techniques of 2D–3D superimposition are widely used in cases of personal identification from video surveillance systems. However, the progressive improvement of 3D image acquisition technology will enable operators to perform also 3D–3D facial superimposition. This study aims at analyzing the possible applications of 3D–3D superimposition to personal identification, although from a theoretical point of view. Twenty subjects underwent a facial 3D scan by stereophotogrammetry twice at different time periods. Scans were superimposed two by two according to nine landmarks, and root‐mean‐square (RMS) value of point‐to‐point distances was calculated. When the two superimposed models belonged to the same individual, RMS value was 2.10 mm, while it was 4.47 mm in mismatches with a statistically significant difference (p < 0.0001). This experiment shows the potential of 3D–3D superimposition: Further studies are needed to ascertain technical limits which may occur in practice and to improve methods useful in the forensic practice.
Spatial and Temporal Evaluation of Hydrological Response to Climate and Land Use Change in Three South Dakota Watersheds
Authors: Paul Manashi , Rajib Mohammad Adnan , Ahiablame Laurent
Published: November 2016

This study analyzed changes in hydrology between two recent decades (1980s and 2010s) with the Soil and Water Assessment Tool (SWAT) in three representative watersheds in South Dakota: Bad River, Skunk Creek, and Upper Big Sioux River watersheds. Two SWAT models were created over two discrete time periods (1981‐1990 and 2005‐2014) for each watershed. National Land Cover Datasets 1992 and 2011 were, respectively, ingested into 1981‐1990 and 2005‐2014 models, along with corresponding weather data, to enable comparison of annual and seasonal runoff, soil water content, evapotranspiration (ET), water yield, and percolation between these two decades. Simulation results based on the calibrated models showed that surface runoff, soil water content, water yield, and percolation increased in all three watersheds. Elevated ET was also apparent, except in Skunk Creek watershed. Differences in annual water balance components appeared to follow changes in land use more closely than variation in precipitation amounts, although seasonal variation in precipitation was reflected in seasonal surface runoff. Subbasin‐scale spatial analyses revealed noticeable increases in water balance components mostly in downstream parts of Bad River and Skunk Creek watersheds, and the western part of Upper Big Sioux River watershed. Results presented in this study provide some insight into recent changes in hydrological processes in South Dakota watersheds. Editor's note: This paper is part of the featured series on SWAT Applications for Emerging Hydrologic and Water Quality Challenges. See the February 2017 issue for the introduction and background to the series.
The oil‐contaminated soil diazotroph Azoarcus oleariusDQS‐4T is genetically and phenotypically similar to the model grass endophyte Azoarcus sp. BH72
Authors: Faoro Helisson , Rene Menegazzo Rodrigo , Battistoni Federico , Gyaneshwar Prasad , do Amaral Fernanda P. , Taulé Cecilia , Rausch Sydnee , Gonçalves Galvão Patricia , de los Santos Cecilia , Mitra Shubhajit , Heijo Gabriela , Sheu Shih‐Yi , Chen Wen‐Ming , Mareque Cintia , Zibetti Tadra‐Sfeir Michelle , Ivo Baldani J. , Maluk Marta , Paula Guimarães Ana , Stacey Gary , de Souza Emanuel M. , Pedrosa Fabio O. , Magalhães Cruz Leonardo , James Euan K.
Published: November 2016

The genome of Azoarcus olearius DQS‐4T, a N2‐fixing Betaproteobacterium isolated from oil‐contaminated soil in Taiwan, was sequenced and compared with other Azoarcus strains. The genome sequence showed high synteny with Azoarcus sp. BH72, a model endophytic diazotroph, but low synteny with five non‐plant‐associated strains (Azoarcus CIB, Azoarcus EBN1, Azoarcus KH32C, A. toluclasticus MF63T and Azoarcus PA01). Average Nucleotide Identity (ANI) revealed that DQS‐4T shares 98.98% identity with Azoarcus BH72, which should now be included in the species A. olearius. The genome of DQS‐4T contained several genes related to plant colonization and plant growth promotion, such as nitrogen fixation, plant adhesion and root surface colonization. In accordance with the presence of these genes, DQS‐4T colonized rice (Oryza sativa) and Setaria viridis, where it was observed within the intercellular spaces and aerenchyma mainly of the roots. Although they promote the growth of grasses, the mechanism(s) of plant growth promotion by A. olearius strains is unknown, as the genomes of DQS‐4T and BH72 do not contain genes for indole acetic acid (IAA) synthesis nor phosphate solubilization. In spite of its original source, both the genome and behaviour of DQS‐4T suggest that it has the capacity to be an endophytic, nitrogen‐fixing plant growth‐promoting bacterium.
A permutation approach for inferring species networks from gene trees in polyploid complexes by minimising deep coalescences
Authors: Oberprieler Christoph , Wagner Florian , Tomasello Salvatore , Konowalik Kamil
Published: November 2016

Context and purpose. Due to ubiquity of polyploid species formation in angiosperms, reconstructing the evolutionary history of polyploid complexes is at the forefront of methodological field of activity in molecular phylogenetics and systematic botany. The advent of multilocus species tree reconstruction approaches motivated by next‐generation sequencing methods pave the way to species network inference methods, with which phylogenetics could accommodate to the necessity for reconstructing reticulate relationships among diploids and (allo‐)polyploids in an objective manner, simultaneously taking into account gene tree incongruences caused by incomplete lineage sorting and hybridisation.

Methods used. The present contribution describes a relatively simple and fast workflow pipeline for the reconstruction of species networks in polyploid complexes based on multilocus gene trees. It uses a permutation strategy and a parsimony‐based principle in species tree reconstruction (Minimising Deep Coalescences,MDC) for the assignment of homoeologs to parental genomes in allopolyploids, which is a crucial step in species network inference for polyploid complexes. Simulations with varying effective population sizes, different temporal scenarios for diploid or polyploid formations and different types of allopolyploid speciation (sister‐species diploids, non‐sister diploids or polyploidisation under participation of ancestral diploids) are used to assess the reliability of the reconstruction.

Main results. Simulations show that the proposed method leads to trustworthy reconstructions if effective populations sizes are not too large and divergences among ancestral taxa are not too shallow. The applicability of our method to a real data set is demonstrated by inferring the reticulate relationships among diploid, tetraploid and hexaploid representatives of the genusLeucanthemopsis(Compositae, Anthemideae) based on gene tree topologies from four nuclear single‐copy genes and two plastidic intergenic spacer regions.

Conclusion. The proposedMDC‐based method for species network reconstruction in polyploids is fast and manages to trustworthily reconstruct parentage in polyploidisation events. Concerns with and possible improvements of the described method are discussed.
Chloroprocaine 10 mg/ml for low‐dose spinal anaesthesia in perianal surgery – a randomised dose finding study
Authors: Gebhardt V. , Mueller‐Hansen L. , Schwarz A. , Bussen D. , Weiss C. , Schmittner M. D.
Published: November 2016

Background

Low‐dose spinal anaesthesia is a safe and reliable anaesthesia technique in outpatient perianal surgery. Regarding its short duration of action and its trend to hyperbaric characteristics, plain chloroprocaine 10 mg/ml seems to be ideal to perform low‐dose spinal anaesthesia. The aim of this trial was to determine the optimal dosage of chloroprocaine for this indication.

Methods

Hundred and twenty patients undergoing perianal surgery were enrolled and randomly allocated to receive 10, 20 or 30 mg of chloroprocaine 10 mg/ml intrathecally. Patients had to sit upright for at least 10 min after injection. We measured the expansion of sensory and motor block and the times until voiding, walking without assistance and home discharge.

Results

The expansion of the sensory (P ≤ 0.0059) and the motor block (P ≤ 0.0086) gained with increasing doses. At a dose of 30 mg the incidence of a profound, clinically relevant motor block was significantly higher compared to 10 and 20 mg (P ≤ 0.0004). In the 10 mg group two patients suffered from nociceptive pain due to an incomplete block and five patients announced discomfort during procedure. Doses of 10 and 20 mg led to a significantly earlier discharge compared to 30 mg (P = 0.0003; P = 0.0406).

Conclusion

Plain chloroprocaine 10 mg/ml can successfully be used for low‐dose spinal anaesthesia in perianal outpatient surgery. Regarding the unfavourable motor block and later discharge‐times in the 30 mg group on the one hand and the block‐failures in the 10 mg group on the other, 20 mg can be recommended as the optimal dose.
An observational study of the macro‐ and micro‐haemodynamic implications of epidural anaesthesia in children
Authors: Triffterer L. , Marhofer P. , Lechner G. , Marksz T. C. , Kimberger O. , Schmid W. , Marhofer D.
Published: November 2016

The haemodynamic implications of epidural anaesthesia in children are poorly documented. We report macro‐ and micro‐haemodynamic data from an observational study of 25 children ranging from neonates to six‐years old, who underwent surgery conducted with a specific combination of monitoring systems. We analysed 90 min of study‐related monitoring after epidural catheterisation, with skin incision taking place after around 30 min. We recorded macrohaemodynamic parameters (monitored using LiDCOrapid) including heart rate, mean arterial pressure, cardiac output, stroke volume, systemic vascular resistance and stroke volume variation. Microhaemodynamic parameters (monitored using Invos™) included cerebral and peri‐renal oxygenation. Based on the entire 90 min of study‐related monitoring, we found significant increases in cardiac output (p = 0.009), stroke volume (p = 0.006) and stroke volume variation (p = 0.008), as well as decreases in systemic vascular resistance (p = 0.007) around 30 min after epidural blockade. There were no significant changes in heart rate, arterial pressure and cerebral or peri‐renal oxygenation during these 90 min. Considering that the microhaemodynamic parameters were not affected by the macrohaemodynamic changes, we conclude that autoregulation of the brain and the kidneys was maintained in children under epidural anaesthesia.
Statin use and risk of endometrial cancer: a nationwide registry‐based case–control study
Authors: Sperling Cecilie D. , Verdoodt Freija , Friis Søren , Dehlendorff Christian , Kjaer Susanne K.
Published: November 2016

Introduction

Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry‐based case–control study, we examined the association between statin use and risk of endometrial cancer.

Material and methods

Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000–2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk‐set sampling. Ever use of statin was defined as two or more prescriptions on separate dates. Conditional logistic regressions were used to estimate age‐matched (by design) and multivariable‐adjusted odds ratios (ORs) and 95% confidence intervals (CI) for endometrial cancer associated with statin use. The multivariable‐adjusted models included parity, hormone replacement therapy (HRT), obesity, diabetes, chronic obstructive pulmonary disease and education. We evaluated whether the association between statin use and endometrial cancer varied with duration and intensity of statin use, type of endometrial cancer or patient characteristics.

Results

The study population comprised 5382 endometrial cancer cases and 72 127 population controls. We observed no association between ever use of statins and endometrial cancer risk (OR 1.03, 95% CI 0.94–1.14). In addition, endometrial cancer risk did not vary substantially with duration or intensity of statin use. Stratification by type of endometrial cancer also yielded neutral ORs.

Conclusions

In our nationwide case–control study, we found no association between statin use and risk of endometrial cancer.
Consensus report: faecal microbiota transfer – clinical applications and procedures
Authors: König J. , Siebenhaar A. , Högenauer C. , Arkkila P. , Nieuwdorp M. , Norén T. , Ponsioen C. Y. , Rosien U. , Rossen N. G. , Satokari R. , Stallmach A. , de Vos W. , Keller J. , Brummer R. J.
Published: November 2016

Background

Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication.

Aim

To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT.

Methods

Well‐acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors.

Results

Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe‐complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings.

Conclusions

Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.
Electrocardiogram Alterations Associated With Psychotropic Drug Use and CACNA1C Gene Variants in Three Independent Samples
Authors: Fabbri Chiara , Boriani Giuseppe , Diemberger Igor , Filippi Maria Giulia , Ravegnini Gloria , Hrelia Patrizia , Minarini Alessandro , Albani Diego , Forloni Gianluigi , Angelini Sabrina , Serretti Alessandro
Published: November 2016

Several antipsychotics and antidepressants have been associated with QTc prolongation or other electrocardiogram (ECG) alterations, but their impact is still debated and other risk factors are known to affect QTc. We investigated the effect of antidepressants and antipsychotics on QTc and other ECG intervals/waves in three samples. Two discovery samples (cross‐sectional sample n = 145 and prospective sample n = 68, naturalistic treatment) and a replication prospective sample (Clinical Antipsychotic Trials of Intervention Effectiveness, n = 515, randomized treatment) were analysed. In both prospective samples, baseline/follow‐up changes in ECG parameters were analysed in relation to the number of psychotropic drugs stratified according to their known cardiovascular risk. In the cross‐sectional sample, ECG parameters were compared among drugs with different risk profile. The possible effect of single nucleotide polymorphisms (SNPs) in the CACNA1C gene on QTc was also investigated. There was no evidence of mean QTc prolongation or increased risk of clinically relevant QTc prolongation (≥20 msec.) in association with psychotropic drugs stratified according to their known cardiovascular risk. The prescription of drugs with cardiovascular risk was less common in older individuals or individuals with cardiovascular comorbidities. Other factors (gender, baseline QTc, renal function) affected QTc. rs1006737 and SNPs in linkage disequilibrium with it modulated QTc duration/changes in all samples. An association between risk drugs and shorter RR interval or higher heart rate was found in all samples. A relevant effect of psychotropic drugs with cardiovascular risk on QTc duration was not observed. A number of factors other than psychotropic drugs may influence QTc. CACNA1C rs1006737 may modulate QTc in patients treated with psychotropic drugs.
Estimation of the Optimal Regime in Treatment of Prostate Cancer Recurrence from Observational Data Using Flexible Weighting Models
Authors: Shen Jincheng , Wang Lu , Taylor Jeremy M. G.
Published: November 2016

Prostate cancer patients are closely followed after the initial therapy and salvage treatment may be prescribed to prevent or delay cancer recurrence. The salvage treatment decision is usually made dynamically based on the patient's evolving history of disease status and other time-dependent clinical covariates. A multi-center prostate cancer observational study has provided us data on longitudinal prostate specific antigen (PSA) measurements, time-varying salvage treatment, and cancer recurrence time. These data enable us to estimate the best dynamic regime of salvage treatment, while accounting for the complicated confounding of time-varying covariates present in the data. A Random Forest based method is used to model the probability of regime adherence and inverse probability weights are used to account for the complexity of selection bias in regime adherence. The optimal regime is then identified by the largest restricted mean survival time. We conduct simulation studies with different PSA trends to mimic both simple and complex regime adherence mechanisms. The proposed method can efficiently accommodate complex and possibly unknown adherence mechanisms, and it is robust to cases where the proportional hazards assumption is violated. We apply the method to data collected from the observational study and estimate the best salvage treatment regime in managing the risk of prostate cancer recurrence.
Model Averaged Double Robust Estimation
Authors: Cefalu Matthew , Dominici Francesca , Arvold Nils , Parmigiani Giovanni
Published: November 2016

Researchers estimating causal effects are increasingly challenged with decisions on how to best control for a potentially high-dimensional set of confounders. Typically, a single propensity score model is chosen and used to adjust for confounding, while the uncertainty surrounding which covariates to include into the propensity score model is often ignored, and failure to include even one important confounder will results in bias. We propose a practical and generalizable approach that overcomes the limitations described above through the use of model averaging. We develop and evaluate this approach in the context of double robust estimation. More specifically, we introduce the model averaged double robust (MA-DR) estimators, which account for model uncertainty in both the propensity score and outcome model through the use of model averaging. The MA-DR estimators are defined as weighted averages of double robust estimators, where each double robust estimator corresponds to a specific choice of the outcome model and the propensity score model. The MA-DR estimators extend the desirable double robustness property by achieving consistency under the much weaker assumption that either the true propensity score model or the true outcome model be within a specified, possibly large, class of models. Using simulation studies, we also assessed small sample properties, and found that MA-DR estimators can reduce mean squared error substantially, particularly when the set of potential confounders is large relative to the sample size. We apply the methodology to estimate the average causal effect of temozolomide plus radiotherapy versus radiotherapy alone on one-year survival in a cohort of 1887 Medicare enrollees who were diagnosed with glioblastoma between June 2005 and December 2009.
Antigen specificity determines anti‐red blood cell IgG‐Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn
Authors: Sonneveld Myrthe E. , Koelewijn Joke , de Haas Masja , Admiraal Jon , Plomp Rosina , Koeleman Carolien A. M. , Hipgrave Ederveen Agnes L. , Ligthart Peter , Wuhrer Manfred , van der Schoot C. Ellen , Vidarsson Gestur
Published: November 2016

Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti‐RBC IgG alloantibodies. HDFN is most often caused by anti‐D but may also occur due to anti‐K, ‐c‐ or ‐E. We recently found N‐linked glycosylation of anti‐D to be skewed towards low fucosylation, thereby increasing the affinity to IgG‐Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. Here, we analysed 230 pregnant women with anti‐c, ‐E or –K alloantibodies from a prospective screening cohort and investigated the type of Fc‐tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. Anti‐c, ‐E and –K show – independent of the event that had led to immunisation – a different kind of Fc‐glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti‐D. High Fc‐galactosylation and sialylation of anti‐c correlated with HDFN disease severity, while low anti‐K Fc‐fucosylation correlated with severe fetal anaemia. IgG‐Fc glycosylation of anti‐RBC antibodies is shaped depending on the antigen. These features influence their clinical potency and may therefore be used to predict severity and identify those needing treatment.
Comprehensive genetic characterization of rosette‐forming glioneuronal tumors: independent component analysis by tissue microdissection
Authors: Kitamura Yohei , Komori Takashi , Shibuya Makoto , Ohara Kentaro , Saito Yuko , Hayashi Saeko , Sasaki Aya , Nakagawa Eiji , Tomio Ryosuke , Kakita Akiyoshi , Nakatsukasa Masashi , Yoshida Kazunari , Sasaki Hikaru
Published: November 2016

A rosette‐forming glioneuronal tumor (RGNT) is a rare mixed neuronal‐glial tumor characterized by biphasic architecture of glial and neurocytic components. The number of reports of genetic analyses of RGNTs is few. Additionally, the genetic background of the unique biphasic pathological characteristics of such mixed neuronal‐glial tumors remains unclear. To clarify the genetic background of RGNTs, we performed separate comprehensive genetic analyses of glial and neurocytic components of five RGNTs, by tissue microdissection. Two missense mutations in FGFR1 in both components of two cases, and one mutation in PIK3CA in both components of one case, were detected. In the latter case with PIK3CA mutation, the additional FGFR1 mutation was detected only in the glial component. Moreover, the loss of chromosome 13q in only the neurocytic component was observed in one other case. Their results suggested that RGNTs, which are tumors harboring two divergent differentiations that arose from a single clone, have a diverse genetic background. Although previous studies have suggested that RGNTs and pilocytic astrocytomas (PAs) represent the same tumor entity, their results confirm that the genetic background of RGNTs is not identical to that of PA.
Novel mutations in KARS cause hypertrophic cardiomyopathy and combined mitochondrial respiratory chain defect
Authors: Verrigni D. , Diodato D. , Di Nottia M. , Torraco A. , Bellacchio E. , Rizza T. , Tozzi G. , Verardo M. , Piemonte F. , Tasca G. , D'Amico A. , Bertini E. , Carrozzo R.
Published: November 2016

Mutations in KARS, which encodes for both mitochondrial and cytoplasmic lysyl‐tRNA synthetase, have been so far associated with three different phenotypes: the recessive form of Charcot–Mary–Tooth polyneuropathy, the autosomal recessive nonsyndromic hearing loss and the last recently described condition related to congenital visual impairment and progressive microcephaly. Here we report the case of a 14‐year‐old girl with severe cardiomyopathy associated to mild psychomotor delay and mild myopathy; moreover, a diffuse reduction of cytochrome C oxidase (COX, complex IV) and a combined enzymatic defect of complex I (CI) and complex IV (CIV) was evident in muscle biopsy. Using the TruSight One sequencing panel we identified two novel mutations in KARS. Both mutations, never reported previously, occur in a highly conserved region of the catalytic domain and displayed a dramatic effect on KARS stability. Structural analysis confirmed the pathogenic role of the identified variants. Our findings confirm and emphasize that mt‐aminoacyl‐tRNA synthetases (mt‐ARSs) enzymes are related to a broad clinical spectrum due to their multiple and still unknown functions.
Anomalies in human sex determination provide unique insights into the complex genetic interactions of early gonad development
Authors: Bashamboo A. , Eozenou C. , Rojo S. , McElreavey K.
Published: November 2016

Human sex determination (SD) involves complex mutually antagonistic genetic interactions of testis‐ and ovary‐determining pathways. For many years, both male and female SD were considered to be regulated by a linear cascade of pro‐male and pro‐female genes, respectively; however, it has become clear that male and female development is achieved through the repression of the alternative state. A gene determining the formation of a testis may function by repressing the female state and vice versa. Uniquely in development, SD is achieved by suppression of the alternate fate and maintained in adulthood by a mutually antagonistic double‐repressive pathway. Here, we review genetic data generated through large‐scale sequencing approaches that are changing our view of how this system works, including the recently described recurrent NR5A1 p.R92W mutation associated with testis development in 46,XX children. We also review some of the unique challenges in the field to establish that mutations, such as this are pathogenic. The impending surge of new genetic data on human SD from sequencing projects will create opportunities for the development of mechanistic models that will clarify how the system operates and importantly provide data to understand how selection and developmental processes interact to direct the evolution of SD across species.
Occupational syncarcinogenesis in the skin – combined effects of two carcinogens from the German occupational disease list
Authors: Dickel Heinrich , Blome Otto , Dickel Beate , Bruckner Thomas , Stockfleth Eggert , Soemantri Silas Paras
Published: November 2016

Background

Though scientifically undisputed, cutaneous syncarcinogenesis is not reflected in German occupational disease (OD) regulations, which tend to be guided by the tenet of monocausality. Recognition of nonmelanoma skin cancer (NMSC) and its precursor lesions as OD requires individual assessment as to whether the requirements pursuant to either OD 5103 (occupational exposure to natural UV radiation) or OD 5102 (occupational exposure to polycyclic aromatic hydrocarbons) are fulfilled.

Methods

Retrospective analysis of 28 patients (median age 72.5 years) with NMSC and respective precursor lesions who had been occupationally exposed to natural UV radiation and polycyclic aromatic hydrocarbons. All cases had undergone expert medical assessment between September 2012 and September 2015.

Results

According to our assessments, all 28 cases met the occupational requirements pursuant to OD 5103 and 5102. In 26 cases (93 %), we recommended recognition of skin cancer as occupational disease pursuant to both OD 5103 and OD 5102. The competent occupational insurance association (BG) followed our recommendation in four cases. In eight cases, recognition was solely based on OD 5103; in ten cases, only on OD 5102. Four cases were denied recognition.

Conclusions

Following adequate cumulative occupational exposure to natural UV light as well as occupational exposure to polycyclic aromatic hydrocarbons, NMSC or its precursor lesions arising in UV‐exposed areas should be reported to the competent occupational insurance association as “OD 5103 and 5102 in terms of syncarcinogenesis”. Apart from the fact that the ensuing recognition proceedings will be able to more adequately reflect real‐life workplace conditions, filing a report pursuant to both ODs also allows for recognition of basal cell carcinoma as occupational disease. According to current regulations, this would not be possible, if the assessment were solely based on OD 5103.
Heavy loads of parasitic freshwater pearl mussel (Margaritifera margaritiferaL.) larvae impair foraging, activity and dominance performance in juvenile brown trout (Salmo truttaL.)
Authors: Filipsson Karl , Petersson Tina , Höjesjö Johan , Piccolo John J. , Näslund Joacim , Wengström Niklas , Österling E. Martin
Published: November 2016

The life cycle of the endangered freshwater pearl mussel (Margaritifera margaritifera) includes a parasitic larval phase (glochidia) on the gills of a salmonid host. Glochidia encystment has been shown to affect both swimming ability and prey capture success of brown trout (Salmo trutta), which suggests possible fitness consequences for host fish. To further investigate the relationship between glochidia encystment and behavioural parameters in brown trout, pairs (n = 14) of wild‐caught trout (infested vs. uninfested) were allowed to drift feed in large stream aquaria and foraging success, activity, agonistic behaviour and fish coloration were observed. No differences were found between infested and uninfested fish except for in coloration, where infested fish were significantly darker than uninfested fish. Glochidia load per fish varied from one to several hundred glochidia, however, and high loads had significant effects on foraging, activity and behaviour. Trout with high glochidia loads captured less prey, were less active and showed more subordinate behaviour than did fish with lower loads. Heavy glochidia loads therefore may negatively influence host fitness due to reduced competitive ability. These findings have implications not only for management of mussel populations in the streams, but also for captive breeding programmes which perhaps should avoid high infestation rates. Thus, low levels of infestation on host fish which do not affect trout behaviour but maintains mussel populations may be optimal in these cases.
Deficit in acoustic signal‐in‐noise detection in glycine receptor α3 subunit knockout mice
Authors: Tziridis Konstantin , Buerbank Stefanie , Eulenburg Volker , Dlugaiczyk Julia , Schulze Holger
Published: November 2016

Hearing is an essential sense for communication in animals and humans. Normal function of the cochlea of higher vertebrates relies on a fine‐tuned interplay of afferent and efferent innervation of both inner and outer hair cells. Efferent inhibition is controlled via olivocochlear feedback loops, mediated mainly by acetylcholine, γ‐aminobutyric acid (GABA) and glycine, and is one of the first sites affected by synapto‐ and neuropathy in the development of hearing loss. While the functions of acetylcholine, GABA and other inhibitory transmitters within these feedback loops are at least partially understood, especially the function of glycine still remains elusive. To address this question, we investigated hearing in glycine receptor (GlyR) α3 knockout (KO) and wildtype (WT) mice. We found no differences in pure tone hearing thresholds at 11.3 and 16 kHz between the two groups as assessed by auditory brainstem response (ABR) measurements. Detailed analysis of the ABR waves at 11.3 kHz, however, revealed a latency decrease of wave III and an amplitude increase of wave IV in KO compared to WT animals. GlyRα3 KO animals showed significantly impaired prepulse inhibition of the auditory startle response in a noisy environment, indicating that GlyRα3‐mediated glycinergic inhibition is important for signal‐in‐noise detection.
Possible role of calcitonin gene‐related peptide in trigeminal modulation of glomerular microcircuits of the rodent olfactory bulb
Authors: Genovese Federica , Bauersachs Hanke Gwendolyn , Gräßer Ines , Kupke Janina , Magin Laila , Daiber Philipp ,   Sertel‐Nakajima , Möhrlen Frank , Messlinger Karl , Frings Stephan
Published: November 2016

Chemosensation in the mammalian nose comprises detection of odorants, irritants and pheromones. While the traditional view assigned one distinct sub‐system to each stimulus type, recent research has produced a more complex picture. Odorants are not only detected by olfactory sensory neurons but also by the trigeminal system. Irritants, in turn, may have a distinct odor, and some pheromones are detected by the olfactory epithelium. Moreover, it is well‐established that irritants change odor perception and vice versa. A wealth of psychophysical evidence on olfactory‐trigeminal interactions in humans contrasts with a paucity of structural insight. In particular, it is unclear whether the two systems communicate just by sharing stimuli, or whether neuronal connections mediate cross‐modal signaling. One connection could exist in the olfactory bulb which performs the primary processing of olfactory signals and receives trigeminal innervation. In the present study, neuroanatomical tracing of the mouse ethmoid nerve illustrates how peptidergic fibers enter the glomerular layer of the olfactory bulb, where local microcircuits process and filter the afferent signal. Biochemical assays reveal release of calcitonin gene‐related peptide from olfactory bulb slices and attenuation of cAMP signaling by the neuropeptide. In the non‐stimulated tissue, the neuropeptide specifically inhibited the basal activity of calbindin‐expressing periglomerular interneurons, but did not affect the basal activity of neurons expressing calretinin, parvalbumin, or tyrosine hydroxylase, nor the activity of astrocytes. This study represents a first step toward understanding trigeminal neuromodulation of olfactory‐bulb microcircuits and provides a working hypothesis for trigeminal inhibition of olfactory signal processing.
Effect of preceding stimulation on sound localization and its representation in the auditory midbrain
Authors: Tolnai Sandra , Beutelmann Rainer , Klump Georg M.
Published: November 2016

Prior stimulation can influence the perception of sound source location. Some psychophysical sound localization procedures differ in the amount of prior stimulation, which may affect measures of localization accuracy. If and how particularly the number of preceding stimuli affects sound localization and the neural representation of sound source position has not been investigated so far and will be the focus of the present report. We trained Mongolian gerbils in a left/right discrimination task where the target stimulus was preceded by silence or followed a number of reference stimuli. Localization thresholds decreased with the number of references presented before the target stimulus. The smallest thresholds were found after the presentation of a train of 5 reference stimuli and after silence. We recorded from units in the inferior colliculus (IC) of anaesthetized gerbils using virtual‐acoustic space stimuli mimicking the ones used in the behavioural task and applied signal detection theory to compare behavioural and neurometric thresholds. We found that neurometric thresholds based on spike rate information of single units covered a wide range of threshold values but only neurometric thresholds that were based on responses of small populations of IC units reached consistently thresholds we also observed in the behavioural experiment. Unlike behavioural thresholds, however, neurometric thresholds were independent of the number of reference stimuli suggesting that processing stages downstream from the IC might better reflect the effect of prior stimulation.
A genome scan for selection signatures comparing farmed Atlantic salmon with two wild populations: Testing colocalization among outlier markers, candidate genes, and quantitative trait loci for production traits
Authors: Liu Lei , Ang Keng Pee , Elliott J. A. K. , Kent Matthew Peter , Lien Sigbjørn , MacDonald Danielle , Boulding Elizabeth Grace
Published: November 2016

Comparative genome scans can be used to identify chromosome regions, but not traits, that are putatively under selection. Identification of targeted traits may be more likely in recently domesticated populations under strong artificial selection for increased production. We used a North American Atlantic salmon 6K SNP dataset to locate genome regions of an aquaculture strain (Saint John River) that were highly diverged from that of its putative wild founder population (Tobique River). First, admixed individuals with partial European ancestry were detected using STRUCTURE and removed from the dataset. Outlier loci were then identified as those showing extreme differentiation between the aquaculture population and the founder population. All Arlequin methods identified an overlapping subset of 17 outlier loci, three of which were also identified by BayeScan. Many outlier loci were near candidate genes and some were near published quantitative trait loci (QTLs) for growth, appetite, maturity, or disease resistance. Parallel comparisons using a wild, nonfounder population (Stewiacke River) yielded only one overlapping outlier locus as well as a known maturity QTL. We conclude that genome scans comparing a recently domesticated strain with its wild founder population can facilitate identification of candidate genes for traits known to have been under strong artificial selection.
Experimental evolution to increase the efficacy of the entomopathogenic fungus Beauveria bassiana against malaria mosquitoes: Effects on mycelial growth and virulence
Authors: Valero‐Jiménez Claudio A. , van Kan Jan A. L. , Koenraadt Constantianus J. M. , Zwaan Bas J. , Schoustra Sijmen E.
Published: November 2016

Entomopathogenic fungi such as Beauveria bassiana are currently considered as a potential control agent for malaria mosquitoes. The success of such strategies depends among others on the efficacy of the fungus to kill its hosts. As B. bassiana can use various resources for growth and reproduction, increasing the dependency on mosquitoes as a nutritional source may be instrumental for reaching this goal. Passage of entomopathogenic fungi through an insect host has been shown to increase its virulence. We evaluated the virulence, fungal outgrowth, mycelial growth rate, and sporulation rate of two B. bassiana isolates (Bb1520 and Bb8028) that underwent 10 consecutive selection cycles through malaria mosquitoes (Anopheles coluzzii) using an experimental evolution approach. This cycling resulted in an altered capacity of evolved B. Bassiana lineages to grow on different substrates while maintaining the ability to kill insects. Notably, however, there were no significant changes in virulence or speed of outgrowth when comparing the evolved lineages against their unevolved ancestors. These results suggest that fungal growth and sporulation evolved through successive and exclusive use of an insect host as a nutritional resource. We discuss the results in light of biocontrol and provide suggestions to increase fungal virulence.
Bad air gets under your skin
Authors: Koohgoli Roxanna , Hudson Laura , Naidoo Khimara , Wilkinson Simon , Chavan Bhaven , Birch‐Machin Mark A.
Published: November 2016

Air pollution is increasing beyond previous estimates and is viewed as the world's largest environmental health risk factor. Numerous clinical and epidemiological studies have highlighted the adverse effects of environmental pollutants on health. Although there is comparatively less research investigating the cutaneous effects of ambient pollution, there is growing recognition of the adverse effects on skin. In this article, we provide an overview of the nature of environmental pollution and highlight the current evidence detailing the effects on cutaneous health. There is convincing evidence demonstrating that air pollution has a detrimental impact on skin and can exacerbate skin disease. Further epidemiological and experimental studies are required to assess the short‐ and long‐term deleterious effects of ambient pollutant exposure on skin. The future challenge would be to use this evidence to develop specific strategies to protect against pollution‐induced damage and prevent the effects of “bad air getting under our skin.”
Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy
Authors: Tietze Julia K. , Angelova Daniela , Heppt Markus V. , Ruzicka Thomas , Berking Carola
Published: November 2016

The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T‐cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56dim and CD56bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56dim NK cells, whereas the baseline levels of CD56bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56dim and CD56bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56dim NK cells as well as normal baseline levels of CD56bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD56dim and CD56bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab.