bluuebunny/crossref_metadata_2025 huggingface dataset:
BRM Promoter Polymorphisms and Survival of Advanced Non–Small Cell Lung Cancer Patients in the Princess Margaret Cohort and CCTG BR.24 Trial
Authors: Liu Geoffrey , Cuffe Sinead , Liang Shermi , Azad Abul Kalam , Cheng Lu , Brhane Yonathan , Qiu Xin , Cescon David W. , Bruce Jeffrey , Chen Zhuo , Cheng Dangxiao , Patel Devalben , Tse Brandon C. , Laurie Scott A. , Goss Glenwood , Leighl Natasha B. , Hung Rayjean , Bradbury Penelope A. , Seymour Lesley , Shepherd Frances A. , Tsao Ming Sound , Chen Bingshu E. , Xu Wei , Reisman David N.
Published: November 2016

Introduction: BRM, a key catalytic subunit of the SWI/SNF chromatin remodeling complex, is a putative tumor susceptibility gene that is silenced in 15% of non–small cell lung cancer (NSCLC). Two novel BRM promoter polymorphisms (BRM-741 and BRM-1321) are associated with reversible epigenetic silencing of BRM protein expression.

Experimental Design: Advanced NSCLC patients from the Princess Margaret (PM) cohort study and from the CCTG BR.24 clinical trial were genotyped for BRM promoter polymorphisms. Associations of BRM variants with survival were assessed using log-rank tests, the method of Kaplan and Meier, and Cox proportional hazards models. Promoter swap, luciferase assays, and chromatin immunoprecipitation (ChIP) experiments evaluated polymorphism function. In silico analysis of publicly available gene expression datasets with outcome were performed.

Results: Carrying the homozygous variants of both polymorphisms (“double homozygotes”, DH) when compared with those carrying the double wild-type was associated with worse overall survival, with an adjusted hazard ratios (aHR) of 2.74 (95% CI, 1.9–4.0). This was confirmed in the BR.24 trial (aHR, 8.97; 95% CI, 3.3–18.5). Lower BRM gene expression (by RNA-Seq or microarray) was associated with worse outcome (P < 0.04). ChIP and promoter swap experiments confirmed binding of MEF2D and HDAC9 only to homozygotes of each polymorphism, associated with reduced promoter activity in the DH.

Conclusions: Epigenetic regulatory molecules bind to two BRM promoter sequence variants but not to their wild-type sequences. These variants are associated with adverse overall and progression-free survival. Decreased BRM gene expression, seen with these variants, is also associated with worse overall survival. Clin Cancer Res; 23(10); 2460–70. ©2016 AACR.
The Effect of Preservative and Temperature on the Analysis of Circulating Tumor DNA
Authors: Parpart-Li Sonya , Bartlett Bjarne , Popoli Maria , Adleff Vilmos , Tucker Laura , Steinberg Rebecca , Georgiadis Andrew , Phallen Jill , Brahmer Julie , Azad Nilo , Browner Ilene , Laheru Daniel , Velculescu Victor E. , Sausen Mark , Diaz Luis A.
Published: November 2016

Purpose: Analysis of genomic alterations in cell-free DNA (cfDNA) is evolving as an approach to detect, monitor, and genotype malignancies. Methods to separate the liquid from the cellular fraction of whole blood for circulating tumor DNA (ctDNA) analyses have been largely unstudied, although these may be a critical consideration for assay performance.

Experimental Design: To evaluate the influence of blood processing on cfDNA and ctDNA quality and yield, we compared the cfDNA levels in serum with those in plasma. Given the limitations of serum for ctDNA analyses, we evaluated the effects of two plasma processing approaches, K2EDTA and Cell-Free DNA BCT (BCT) tubes, on cfDNA and ctDNA recovery. A total of 45 samples from nine patients with cancer were collected in both tube types. Once collected, blood was processed into plasma immediately or kept at room temperature and processed into plasma at 1, 3, 5, or 7 days.

Results: As early as 24 hours after collection, plasma isolated from blood collected in K2EDTA tubes contained an elevated level of cfDNA that increased over time compared with BCT tubes where no significant increase in cfDNA levels was observed. When samples from an additional six patients with cancer, collected in the same manner, were stored at 4°C in K2EDTA tubes over the course of 3 days, total cfDNA and ctDNA levels were comparable between samples collected in BCT tubes. At day 3, there was a trend toward a decrease in ctDNA levels in both tubes that was more pronounced when measuring the mutant allele fraction for cases stored at 4°C in K2EDTA tubes.

Conclusions: In summary, methods of blood processing have a strong influence on cfDNA and ctDNA levels and should be a consideration when evaluating ctDNA in peripheral circulation. Clin Cancer Res; 23(10); 2471–7. ©2016 AACR.
Isolation of T-Cell Receptors Specifically Reactive with Mutated Tumor-Associated Antigens from Tumor-Infiltrating Lymphocytes Based on CD137 Expression
Authors: Parkhurst Maria , Gros Alena , Pasetto Anna , Prickett Todd , Crystal Jessica S. , Robbins Paul , Rosenberg Steven A.
Published: November 2016

Purpose: The adoptive transfer of lymphocytes genetically modified to express tumor reactive T-cell receptors (TCR) can mediate tumor regression. Some tumor-infiltrating lymphocytes (TIL) recognize somatic mutations expressed only in the patient's tumors, and evidence suggests that clinically effective TILs target tumor-specific neoantigens. Here we attempted to isolate neoantigen-reactive TCRs as a prelude to the treatment of patients with autologous T cells genetically modified to express such TCRs.

Experimental Design: Mutations expressed by tumors were identified using whole-exome and RNA sequencing. Tandem minigene (TMG) constructs encoding 12–24 mutated gene products were synthesized, each encoding the mutated amino acid flanked by 12 amino acids of the normal protein sequence. TILs were cultured with autologous dendritic cells (DC) transfected with in vitro transcribed (IVT) mRNAs encoding TMGs and were evaluated for IFNγ secretion and CD137 expression. Neoantigen-reactive T cells were enriched from TILs by sorting for CD137+ CD8+ T cells and expanded in vitro. Dominant TCR α and β chains were identified in the enriched populations using a combination of 5′ rapid amplification of cDNA ends, deep sequencing of genomic DNA, PairSeq analysis, and single-cell RT-PCR analysis. Human PBL retrovirally transduced to express the TCRs were evaluated for recognition of relevant neoantigens.

Results: We identified 27 TCRs from 6 patients that recognized 14 neoantigens expressed by autologous tumor cells.

Conclusions: This strategy provides the means to generate T cells expressing neoantigen-reactive TCRs for use in future adoptive cell transfer immunotherapy trials for patients with cancer. Clin Cancer Res; 23(10); 2491–505. ©2016 AACR.
The True Story and Advantages of RNA Phage Capsids as Nanotools
Authors: Pumpens Paul , Renhofa Regina , Dishlers Andris , Kozlovska Tatjana , Ose Velta , Pushko Peter , Tars Kaspars , Grens Elmars , Bachmann Martin F.
Published: November 2016

RNA phages are often used as prototypes for modern recombinant virus-like particle (VLP) technologies. Icosahedral RNA phage VLPs can be formed from coat proteins (CPs) and are efficiently produced in bacteria and yeast. Both genetic fusion and chemical coupling have been successfully used for the production of numerous chimeras based on RNA phage VLPs. In this review, we describe advances in RNA phage VLP technology along with the history of the Leviviridae family, including its taxonomical organization, genomic structure, and important role in the development of molecular biology. Comparative 3D structures of different RNA phage VLPs are used to explain the level of VLP tolerance to foreign elements displayed on VLP surfaces. We also summarize data that demonstrate the ability of CPs to tolerate different organic (peptides, oligonucleotides, and carbohydrates) and inorganic (metal ions) compounds either chemically coupled or noncovalently added to the outer and/or inner surfaces of VLPs. Finally, we present lists of nanotechnological RNA phage VLP applications, such as experimental vaccines constructed by genetic fusion and chemical coupling methodologies, nanocontainers for targeted drug delivery, and bioimaging tools.
Occurrence and Origin of Supernumerary Chromosomes in Partamona (Hymenoptera: Apidae: Meliponini)
Authors: Machado Diana P. , Miranda Elder A. , Dessi Mariana C. , Sabadini Camila P. , Del Lama Marco A.
Published: November 2016

Samples from 861 colonies of 12 Partamona species from 125 Brazilian localities were analysed for a SCAR marker specific to the B chromosomes of P. helleri. We identified the SCAR marker in 6 of the 12 species analysed, including 2 (P. gregaria and P. chapadicola) from the pearsoni clade. This is the first report on the presence of this marker in Partamona species that are not included in the cupira clade, which indicates that the B chromosomes probably are more widespread in this genus than previously thought. The analysis revealed a high frequency of the SCAR marker in the samples of P. helleri (0.47), P. cupira (0.46), and P. rustica (0.29), and a low frequency in P. aff. helleri (0.06). The frequency of the marker in P. helleri was correlated with the latitude of the sampling locality, decreasing from north to south. Sequence data on the SCAR marker from 50 individuals of the 6 species in which the presence of this marker was shown revealed a new scenario for the origin of the B chromosomes in Partamona.
Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated With Lower Mortality and Heart Failure Hospitalization Rates in Patients With Heart Failure With Mid-Range and Preserved Ejection Fraction
Authors: Savarese Gianluigi , Hage Camilla , Orsini Nicola , Dahlström Ulf , Perrone-Filardi Pasquale , Rosano Giuseppe M.C. , Lund Lars H.
Published: November 2016

Background—

In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients.

Methods and Results—

In the Swedish Heart Failure Registry, HFmrEF (EF=40%–49%) and HFpEF (EF≥50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median follow-up of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36–0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29–0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34–0.62). These findings were replicated in HFmrEF and HFpEF separately.

Conclusions—

In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.
Angiogenic Imbalance and Residual Myocardial Injury in Recovered Peripartum Cardiomyopathy Patients
Authors: Goland Sorel , Weinstein Jean Marc , Zalik Adi , Kuperstein Rafael , Zilberman Liaz , Shimoni Sara , Arad Michael , Ben Gal Tuvia , George Jacob
Published: November 2016

Background—

Recent studies suggest that angiogenic imbalance during pregnancy may lead to acute peripartum cardiomyopathy (PPCM). We propose that angiogenic imbalance and residual cardiac dysfunction may exist even after recovery from PPCM.

Methods and Results—

Twenty-nine women at least 12 months after presentation with PPCM, who exhibited recovery of left ventricular (LV) ejection fraction (≥50%), were included in the study (mean age 35±6 years, LV ejection fraction 61.0±3.9%). The number of circulating endothelial progenitor cells (EPCs) and plasma levels of proangiogenic vascular endothelial growth factor and of soluble vascular endothelial growth factor receptor Flt1 (sFlt1) were measured. All patients underwent comprehensive cardiac function assessment, including tissue Doppler imaging and 2-dimensional (2D) strain echocardiography. All measurements were compared with healthy controls. Patients with a history of PPCM have significantly higher sFlt1 concentrations (median [25th–75th percentile]; 149.57, [63.14–177.89] versus 20.29, [15.00–53.89] pg/mL,
P
<0.001) and significantly decreased vascular endothelial growth factor/sFlt1 ratio (
P
=0.012) compared with controls, with a trend toward lower concentration of circulating CD34
+
/KDR
+
levels. In addition, patients with PPCM had lower early velocities E′ septal (9.9±2.1 versus 11.0±1.5 cm/s,
P
=0.02), with a significantly lower systolic velocity S′ septal (7.6±1.2 versus 8.5±1.2 cm/s,
P
=0.003) by tissue Doppler imaging. Significantly lower LV global longitudinal (−19.1±3.3 versus −22.7±2.2%,
P
<0.001) and apical circumferential 2D strain (−16.6±4.9 versus −21.2±7.9,
P
=0.02) were present in patients with PPCM compared with controls.

Conclusions—

Higher concentration of sFlt1 with concomitant decreased circulating endothelial progenitor cell levels along with inappropriate attenuated vascular endothelial growth factor levels may imply an angiogenic imbalance that exists even after recovery and may thus predispose to PPCM. In addition, tissue Doppler imaging and 2D strain were able to identify residual myocardial injury in post-PPCM women with apparent recovery of LV systolic function. Both angiogenic imbalance and residual myocardial injury may play an important role in the recurrence of LV dysfunction during subsequent pregnancies.
Incidence and Determinants of Complications in Rotational Atherectomy
Authors: Sakakura Kenichi , Inohara Taku , Kohsaka Shun , Amano Tetsuya , Uemura Shiro , Ishii Hideki , Kadota Kazushige , Nakamura Masato , Funayama Hiroshi , Fujita Hideo , Momomura Shin-ichi
Published: November 2016

Background—

The usage of rotational atherectomy (RA) is growing in the current percutaneous coronary intervention (PCI) because of the expansion of PCI indication to more complex lesions. However, the complications after RA have been linked to procedure-related morbidity and mortality. The purpose of this study was to investigate the incidence and determinants of complications in RA using a large nationwide registration system in Japan (J-PCI).

Methods and Results—

The primary composite outcome of this study was defined as the occurrence of in-hospital death, cardiac tamponade, and emergent surgery after RA. A total of 13 335 RA cases (3.2% of registered PCI cases) were analyzed. The composite outcome was observed in 175 cases (1.31%) and included 80 in-hospital deaths (0.60%), 86 tamponades (0.64%), and 24 emergent surgeries (0.18%). The clinical variables associated with occurrence of the composite outcome were age (odds ratio [OR] 1.03 per unit increment, 95% confidence interval [CI] 1.02–1.05), impaired kidney function (OR 1.59, 95% CI 1.15–2.19), previous myocardial infarction (OR 1.69, 95% CI 1.21–2.35), emergent PCI (OR 4.02, 95% CI 1.66–8.27), and triple-vessel disease (versus single-vessel disease: OR 2.17, 95% CI 1.43–3.28). Notably, institutional volume of RA cases was inversely associated with the composite outcomes (high- versus low-volume institution: OR 0.56, 95% CI 0.36–0.89).

Conclusions—

The reported incidence of important procedure-related complication rate was 1.3%, with each component ranging between 0.2% and 0.6% in J-PCI. Its determinants were both patient related (age, impaired kidney function, and previous myocardial infarction) and procedure related (emergent procedures, number of diseased vessels, and institutional volume of RA).
Analysis of Machine Learning Techniques for Heart Failure Readmissions
Authors: Mortazavi Bobak J. , Downing Nicholas S. , Bucholz Emily M. , Dharmarajan Kumar , Manhapra Ajay , Li Shu-Xia , Negahban Sahand N. , Krumholz Harlan M.
Published: November 2016

Background—

The current ability to predict readmissions in patients with heart failure is modest at best. It is unclear whether machine learning techniques that address higher dimensional, nonlinear relationships among variables would enhance prediction. We sought to compare the effectiveness of several machine learning algorithms for predicting readmissions.

Methods and Results—

Using data from the Telemonitoring to Improve Heart Failure Outcomes trial, we compared the effectiveness of random forests, boosting, random forests combined hierarchically with support vector machines or logistic regression (LR), and Poisson regression against traditional LR to predict 30- and 180-day all-cause readmissions and readmissions because of heart failure. We randomly selected 50% of patients for a derivation set, and a validation set comprised the remaining patients, validated using 100 bootstrapped iterations. We compared C statistics for discrimination and distributions of observed outcomes in risk deciles for predictive range. In 30-day all-cause readmission prediction, the best performing machine learning model, random forests, provided a 17.8% improvement over LR (mean C statistics, 0.628 and 0.533, respectively). For readmissions because of heart failure, boosting improved the C statistic by 24.9% over LR (mean C statistic 0.678 and 0.543, respectively). For 30-day all-cause readmission, the observed readmission rates in the lowest and highest deciles of predicted risk with random forests (7.8% and 26.2%, respectively) showed a much wider separation than LR (14.2% and 16.4%, respectively).

Conclusions—

Machine learning methods improved the prediction of readmission after hospitalization for heart failure compared with LR and provided the greatest predictive range in observed readmission rates.
Identifying Drug–Drug Interactions by Data Mining
Authors: Hansen Peter Wæde , Clemmensen Line , Sehested Thomas S.G. , Fosbøl Emil Loldrup , Torp-Pedersen Christian , Køber Lars , Gislason Gunnar H. , Andersson Charlotte
Published: November 2016

Background—

Knowledge about drug–drug interactions commonly arises from preclinical trials, from adverse drug reports, or based on knowledge of mechanisms of action. Our aim was to investigate whether drug–drug interactions were discoverable without prior hypotheses using data mining. We focused on warfarin–drug interactions as the prototype.

Methods and Results—

We analyzed altered prothrombin time (measured as international normalized ratio [INR]) after initiation of a novel prescription in previously INR-stable warfarin-treated patients with nonvalvular atrial fibrillation. Data sets were retrieved from clinical work. Random forest (a machine-learning method) was set up to predict altered INR levels after novel prescriptions. The most important drug groups from the analysis were further investigated using logistic regression in a new data set. Two hundred and twenty drug groups were analyzed in 61 190 novel prescriptions. We rediscovered 2 drug groups having known interactions (β-lactamase-resistant penicillins [dicloxacillin] and carboxamide derivatives) and 3 antithrombotic/anticoagulant agents (platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors [dabigatran etexilate], and heparins) causing decreasing INR. Six drug groups with known interactions were rediscovered causing increasing INR (antiarrhythmics class III [amiodarone], other opioids [tramadol], glucocorticoids, triazole derivatives, and combinations of penicillins, including β-lactamase inhibitors) and two had a known interaction in a closely related drug group (oripavine derivatives [buprenorphine] and natural opium alkaloids). Antipropulsives had an unknown signal of increasing INR.

Conclusions—

We were able to identify known warfarin–drug interactions without a prior hypothesis using clinical registries. Additionally, we discovered a few potentially novel interactions. This opens up for the use of data mining to discover unknown drug–drug interactions in cardiovascular medicine.
Linkage and Association Analysis Identifies
TRAF1
Influencing Common Carotid Intima–Media Thickness
Authors: Heßler Nicole , Geisel Marie Henrike , Coassin Stefan , Erbel Raimund , Heilmann Stefanie , Hennig Frauke , Hoffmann Barbara , Jöckel Karl-Heinz , Moebus Susanne , Moskau-Hartmann Susanna , Nürnberg Gudrun , Nürnberg Peter , Vens Maren , Klockgether Thomas , Kronenberg Florian , Scherag André , Ziegler Andreas
Published: November 2016

Background and Purpose—

Carotid intima–media thickness is a marker for subclinical atherosclerosis that predicts subsequent clinical cardiovascular events. The aim of this study was to identify chromosomal loci with linkage or association to common carotid intima–media thickness.

Methods—

Nuclear families were recruited using the single parental proband sib-pair design. Genotype data were available for 546 individuals from 132 nuclear families of the Bonn IMT Family Study using the Affymetrix GeneChip Human Mapping 250K Sty chip. Multipoint logarithm of the odds (LOD) scores were determined with the quantitative trait locus statistic implemented in multipoint engine for rapid likelihood. Linkage analysis and family-based association tests were conducted. Data from 2471 German participants from the HNR (Heinz Nixdorf Recall) Study were used for subsequent replication.

Results—

Two new genomic regions with suggestive linkage (LOD>2) were identified on chromosome 4 (LOD=2.26) and on chromosome 17 (LOD=2.01). Previously reported linkage findings were replicated on chromosomes 13 and 14. Fifteen single nucleotide polymorhisms, located on chromosomes 4, 6, and 9, revealed
P
<10
–4
in the family-based association analyses. One of these signals was replicated in HNR (rs2416804, 1-sided
P
=1.60×10
–3
, located in the gene
TRAF1
).

Conclusions—

This study presents the first genome-wide linkage and association study of common carotid intima–media thickness in the German population. Alleles of rs2416804 in
TRAF1
were identified as being linked and associated with carotid intima–media thickness. Further studies are needed to evaluate the contribution of this locus to the development of atherosclerosis.
Selective Sphingosine 1-Phosphate Receptor 1 Agonist Is Protective Against Ischemia/Reperfusion in Mice
Authors: Brait Vanessa H. , Tarrasón Gema , Gavaldà Amadeu , Godessart Núria , Planas Anna M.
Published: November 2016

Background and Purpose—

Growing evidence supports that the immunomodulatory drug fingolimod is protective in stroke. Fingolimod binds to 4 of 5 sphingosine-1-phosphate (S1P) receptors and, among other actions, it induces lymphopenia. In this study, we investigated whether a selective S1P1 agonist is protective in experimental stroke.

Methods—

Drug selectivity was studied in vitro in cells overexpressing the human S1P receptors. Mice (n=54) received different doses of LASW1238 (3 or 10 mg/kg), fingolimod (1 mg/kg), or the vehicle intraperitoneal, and lymphopenia was studied at different time points. After intraluminal middle cerebral artery occlusion for 45 minutes and immediately after reperfusion, mice (n=56) received the drug treatment. At 24 hours, a neurological test was performed and infarct volume was measured. Treatment and all the analyses were performed in a blind fashion.

Results—

In vitro functional assays showed that LASW1238 is a selective agonist of the S1P1 receptor. At 10 mg/kg, this compound induced sustained lymphopenia in mice comparable with fingolimod, whereas at 3 mg/kg it induced short-lasting lymphopenia. After ischemia, both LASW1238 (10 mg/kg) and fingolimod reduced infarct volume, but only LASW1238 (10 mg/kg) showed statistically significant differences versus the vehicle. The neurological function and plasma cytokine levels were not different between groups.

Conclusions—

The selective S1P1 agonist LASW1238 reduces infarct volume after ischemia/reperfusion in mice, but only when lymphopenia is sustained for at least 24 hours. S1P1 and lymphocytes are potential targets for drug treatment in stroke. Defining the best drug dosing regimens to control the extent and duration of lymphopenia is critical to achieve the desired effects.
Fatwa and Propaganda: Contemporary Muslim Responses to the Sudanese Mahdiyya
Authors: Nicoll Fergus
Published: November 2016

The powerful call (daʿwa) of Muḥammad Aḥmad, the self-styled Mahdī, and his ensuing jihad against Ottoman-Egyptian rule in Sudan provoked a variety of responses within the larger Muslim community. The ʿulamāʾ, al-Azhar-trained orthodox legal and religious scholars in Khartoum and Cairo, responded with outrage and detailed legal arguments, challenging the credentials of an individual they insisted was an impostor, and rehearsing instead the legitimacy of the Ottoman Sultan as the bona fide leader of the faithful. Beyond the establishment hierarchy, politically- and religiously-motivated activists and propagandists, in Sudan, Egypt and beyond, joined the debate over Muḥammad Aḥmad’s credibility: at stake was a substantial body of susceptible Muslim opinion, in the Ottoman provinces of the Hejaz and Syria and as far away as British-ruled India. This article describes in detail the spiritual and legal arguments over a personality whose claimed mandate had implications for two of the world’s largest empires.
­­­Laccaria rubroalba sp. nov. (Hydnangiaceae, Agaricales) from Southwestern China
Authors: LUO XIA , YE LEI , CHEN JIE , KARUNARATHNA SAMANTHA C. , XU JIANCHU , HYDE KEVIN D. , MORTIMER PETER E.
Published: November 2016

The novel species Laccaria rubroalba is described from Southwestern China by using both morphological characteristics and molecular data. It is characterized by small basidiomata; reddish white pileus when moist or young, white to pale when dry; 4-spored basidia and globose to broadly ellipsoid, hyaline, moderately echinulate basidiospores. Phylogenetic relationships inferred from ITS sequence data confirmed the separation of this new species from other closely related species in the genus Laccaria. The new species is compared with similar taxa. A description, line drawings and colour photographs of the new species, and phylogenetic tree to show the placement of the new species are provided.
Orthoptera (Insecta: Tettigonioidea, Pyrgomorphoidea, Acridoidea) of Kafa Biosphere Reserve, Bale Mountains National Park and other areas of conservation interest in Ethiopia
Authors: FELIX ROB P.W.H. , MASSA BRUNO
Published: November 2016

An annotated checklist of 51 Orthoptera taxa (Tettigonioidea, Pyrgomorphoidea and Acridoidea) of Kafa Biosphere Reserve, Bale Mountains National Park and some additional sites in Ethiopia is presented. Ten species are newly recorded for the country. Four species are new to science: Peropyrrhicia attilioi n. sp., P. keffensis n. sp., P. semiensis n. sp. and Coryphosima danieli n. sp. The status of Peropyrrhicia cooperi Uvarov, 1934 and P. scotti Uvarov, 1934 is revised: both are considered valid species.
Two new species of the genus Xenotoca Hubbs and Turner, 1939 (Teleostei, Goodeidae) from central-western Mexico
Authors: DOMÍNGUEZ-DOMÍNGUEZ OMAR , BERNAL-ZUÑIGA DULCE MARÍA , PILLER KYLE R.
Published: November 2016

The subfamily Goodeinae (Goodeidae) is one of the most representative and well-studied group of fishes from central Mexico, with around 18 genera and 40 species. Recent phylogenetic studies have documented a high degree of genetic diversity and divergences among populations, suggesting that the diversity of the group may be underestimated. The species Xenotoca eiseni has had several taxonomic changes since its description. Xenotoca eiseni is considered a widespread species along the Central Pacific Coastal drainages of Mexico, inhabiting six independent drainages. Recent molecular phylogenetic studies suggest that X. eiseni is a species complex, represented by at least three independent evolutionary lineages. We carried out a meristic and morphometric study in order to evaluate the morphological differences among these genetically divergent populations and describe two new species. The new species of goodeines, Xenotoca doadrioi and X. lyonsi, are described from the Etzatlan endorheic drainage and upper Coahuayana basin respectively.
Using Synthetic Brightness Temperatures to Address Uncertainties in Cloud-Top-Height Verification
Authors: Nachamkin Jason E. , Jin Yi , Grasso Lewis D. , Richardson Kim
Published: November 2016

Cloud-top verification is inherently difficult because of large uncertainties in the estimates of observed cloud-top height. Misplacement of cloud top associated with transmittance through optically thin cirrus is one of the most common problems. Forward radiative models permit a direct comparison of predicted and observed radiance, but uncertainties in the vertical position of clouds remain. In this work, synthetic brightness temperatures are compared with forecast cloud-top heights so as to investigate potential errors and develop filters to remove optically thin ice clouds. Results from a statistical analysis reveal that up to 50% of the clouds with brightness temperatures as high as 280 K are actually optically thin cirrus. The filters successfully removed most of the thin ice clouds, allowing for the diagnosis of very specific errors. The results indicate a strong negative bias in midtropospheric cloud cover in the model, as well as a lack of land-based convective cumuliform clouds. The model also predicted an area of persistent stratus over the North Atlantic Ocean that was not apparent in the observations. In contrast, high cloud tops associated with deep convection were well simulated, as were mesoscale areas of enhanced trade cumulus coverage in the Sargasso Sea.
Effects of Urban Plume Aerosols on a Mesoscale Convective System
Authors: Kawecki Stacey , Henebry Geoffrey M. , Steiner Allison L.
Published: November 2016

This study examines the effects of urban aerosols on a mesoscale convective system (MCS) in the central Great Plains with the Weather Research and Forecasting Model coupled with chemistry (WRF-Chem). Urban emissions from Kansas City, Missouri, were scaled by factors of 0.5, 1.0, and 2.0 to investigate the impact of urban aerosol load on MCS propagation and strength. The first half of the storm development is characterized by a stationary front to the north of Kansas City (phase I; 1800 UTC 26 May–0600 UTC 27 May), which develops into a squall line south of the urban area (phase II; 0600–1800 UTC 27 May). During phase I, doubling urban emissions shifts the precipitation accumulation, with enhancement downwind of the storm propagation and suppression upwind. During phase II, a squall line develops in the baseline and doubled emissions scenarios but not when emissions are halved. These changes in MCS propagation and strength are a function of cold pool strength, which is determined by microphysical processes and directly influenced by aerosol load. Overall, changes in urban emissions drive changes in cloud microphysics, which trigger large-scale changes in storm morphology and precipitation patterns. These results show that urban emissions can play an important role in mesoscale weather systems.
Lessons and Challenges of Disaster Relief Work in Rural China
Authors: Ren Zhengjia , Dias Jason , Zhang Wei
Published: November 2016

Due to the disastrous Wenchuan earthquake that hit Sichuan, China, on May 12, 2008, approximately 70,000 people died, around 400,000 were injured, 18,467 were missing, and millions were left homeless due to the collapse of their homes. The substantial trauma and loss in the disaster area posed a challenge for disaster relief work focused on survivors’ psychological health. Many of the psychological interventions were based on Western or urban outpatient populations and were thus inappropriate for the uneducated, agriculturally based population of rural China, potentially limiting patient care and sensitivity during this postdisaster relief. This article discusses the therapeutic issues involved and finds that the collectivist nature of the rural Chinese culture and indigenized ways of working with the earthquake survivors are of paramount importance. It adds to the research literature by discussing the importance of relationships through the Chinese concept of Guanxi in the context of disaster relief work in rural China. Consistent with the concept of Guanxi, disaster relief volunteers must fully respect the world of the survivors while remaining flexible and creative in their work to build deeper connections and relationships.
An exploratory international comparison of professional confidence in volunteer policing
Authors: Wolf Ross , Pepper Ian , Dobrin Adam
Published: November 2016

Police volunteers are an important asset to communities and policing agencies but have been relatively understudied. Similar models of police volunteers have developed in the United States and the United Kingdom but these differ in the level of their preparedness and training. This current study utilises vignettes to examine the confidence of volunteer police officers from two agencies, one in the US and one in the UK. Results show that while both groups in the study are confident in their professional ability to handle issues at a policing scene, UK volunteer officers feel less confident about interviewing and administrative paperwork than their US counterparts.
Tilt thresholds for acceleration rendering in driving simulation
Authors: Colombet Florent , Fang Zhou , Kemeny Andras
Published: November 2016

The tilt coordination technique is used in driving simulation for reproducing a sustained linear horizontal acceleration by tilting the simulator cabin. If combined with the translation motion of the simulator, this technique increases the acceleration rendering capabilities of the whole system. To perform this technique correctly, the rotational motion must be slow to remain under the perception threshold and thus be unnoticed by the driver. However, the acceleration to render changes quickly. Between the slow rotational motion limited by the tilt threshold and the fast change of acceleration to render, the design of the coupling between motions of rotation and translation plays a critical role in the realism of a driving simulator. This study focuses on the acceptance by drivers of different configurations for tilt restitution in terms of maximum tilt angle, tilt rate, and tilt acceleration. Two experiments were conducted, focusing respectively on roll tilt for a 0.2 Hz slaloming task and on pitch tilt for an acceleration/deceleration task. The results show what thresholds have to be followed in terms of amplitude, rate, and acceleration. These results are far superior to the standard human perception thresholds found in the literature.
Public support for hosting the Olympic Summer Games in Germany: The CVM approach
Authors: Wicker Pamela , Whitehead John C , Mason Daniel S , Johnson Bruce K
Published: November 2016

Cities and their respective regions must weigh the merits of hosting major sport events, including the Olympic Games. This paper presents a contingent valuation method estimate of the monetary value of intangible benefits to Germans of hosting the Olympic Summer Games. In a nationwide online survey, 6977 respondents said whether they would support a referendum to host the Games. The survey employed a payment card format containing monthly tax amounts to elicit individual willingness-to-pay for the Games over a five-year period. In the weighted sample, 26% expressed an average willingness-to-pay of €51. Willingness-to-pay varied widely across regions. Around Cologne, the average willingness-to-pay was €100. Interval data hurdle models reveal that policy consequentiality and various intangible benefits increased willingness-to-pay. Aggregate willingness-to-pay over a five-year period amounted to €46 billion which exceeded the estimated costs of the 2024 Summer Games for Hamburg. The findings have implications for policy makers since they show what regions within Germany most support hosting the Games.
Amitraz poisoning: an unusual cause of respiratory and peripheral circulatory failure
Authors: Agrawal Ishwar , Ahmad Sohaib , Kumar Manoj , Akram Mohamad
Published: November 2016

We report a case of respiratory failure with unconsciousness in an adult occurring within 1 h of ingestion of a pesticide, amitraz, along with alcohol with a suicidal intent. Although commonly available and potentially fatal, this compound is not usually used as a suicidal agent.
“Opting Out” or “Pushed Out”? Integrating Perspectives on Women’s Career Equality for Gender Inclusion and Interventions
Authors: Kossek Ellen Ernst , Su Rong , Wu Lusi
Published: November 2016

This paper integrates the rapidly growing literatures on the individual and organizational factors that contribute to women’s career equality. We organize studies into three research perspectives: career preference, gender bias, and work-family explanations. These literatures diverge on whether women “opt out” or are “pushed out” of leadership positions in organizations. Further, the interconnectedness of these “pushes” and “pulls” and micro-macro linkages are not well-integrated. This creates a lack of clarity about what scholars should study and what practices organizations should implement. We define women’s career equality as an individual and organizational phenomenon involving the degree to which women (a) have equal access to and participation in career opportunities, and (b) experience equal intrinsic and extrinsic work and nonwork outcomes compared to men. We bridge the interdisciplinary divides by developing an integrative multi-level model of women’s career equality. We propose that individuals’ career perceptions and experiences are embedded in social contexts reflecting the climate for gender inclusion and interact with these contexts to shape women’s career equality outcomes. The climate for gender inclusion has three dimensions: fairness, leveraging talent, and workplace support. We identify coalescing themes to stimulate future research, including attention to national socio-economic influences, improving metrics and measurement of gender inclusion climate, multi-level career equality outcomes, a joint focus on implicit and explicit bias, and designing cross-disciplinary interventions for experiments. In order to foster theory-based research that is linked to practice, we suggest implementing and scientifically evaluating comprehensive workplace interventions that integrate perspectives and levels.
Scandals, Ethics, and Regulatory Change in Biomedical Research
Authors: Hedgecoe Adam
Published: November 2016

This paper explores how a particular form of regulation—prior ethical review of research—developed over time in a specific context, testing the claims of standard explanations for such change (which center on the role of exogenous shocks in the form of research scandals) against more recent theoretical approaches to institutional changes, which emphasize the role of gradual change. To makes its case, this paper draws on archival and interview material focusing on the research ethics review system in the UK National Health Service. Key insights center on the minimal role scandals play in shaping changes in this regulatory setting and how these depend upon the absence of a single coherent profession (and accompanying social contract) associated with biomedical research.
Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging
Authors: Takkinen Jatta S , López-Picón Francisco R , Al Majidi Rana , Eskola Olli , Krzyczmonik Anna , Keller Thomas , Löyttyniemi Eliisa , Solin Olof , Rinne Juha O , Haaparanta-Solin Merja
Published: November 2016

Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer’s disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer’s disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer’s disease using longitudinal in vivo18F-FDG and 18F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n = 9) and wild type control mice (WT, n = 9) were studied longitudinally every third month from age 6 to 15 months with 18F-FDG and 18F-DPA-714 with a one-week interval between the scans. Additional TG (n = 52) and WT (n = 29) mice were used for ex vivo studies. In vivo, the 18F-FDG SUVs were lower and the 18F-DPA-714 binding ratios relative to the cerebellum were higher in the TG mouse cortex and hippocampus than in WT mice at age 12 to 15 months ( p < 0.05). The ex vivo cerebellum binding ratios supported the results of the in vivo18F-DPA-714 studies but not the 18F-FDG studies. This longitudinal PET study demonstrated decreased energy metabolism and increased inflammation in the brains of APP/PS1-21 mice compared to WT mice.
Therapeutic inertia and intensified treatment in diabetes mellitus prescription patterns: A nationwide population-based study in Taiwan
Authors: Huang Li-Ying , Yeh Hseng-Long , Yang Ming-Chin , Shau Wen-Yi , Su Syi , Lai Mei-Shu
Published: November 2016

Objective

To measure therapeutic inertia by characterizing prescription patterns using secondary data obtained from the nationwide diabetes mellitus pay-for-performance (DM-P4P) programme in Taiwan.

Methods

Using reimbursement claims from Taiwan’s National Health Insurance Research Database, a nationwide retrospective cohort study was undertaken of patients with diabetes mellitus who participated in the DM-P4P programme from 2006–2008. Glycosylated haemoglobin results were used to evaluate modifications in therapy in response to poor diabetes control. Prescription patterns were used to assign patients to either a therapeutic inertia group or an intensified treatment group. Therapeutic inertia was defined as the failure to act on a known problem.

Results

The research sample comprised of 168 876 patients with diabetes mellitus who had undergone 899 135 tests. Of these, 37.4% (336 615 visits) of prescriptions were for a combination of two types of drug and 27.7% (248 788 visits) were for a combination of three types of drug. The proportion of patients in the intensified therapy group who were prescribed more than two types of drug was considerably higher than that in the therapeutic inertia group.

Conclusion

In many cases in the therapeutic inertia group only a single type of hypoglycaemic drug was prescribed or the dosage remained unchanged.
The adaption and evaluation of a Latvian version of the National Institutes of Health Stroke Scale
Authors: Jurjāns Kristaps , Noviks Iļja , Volčeka Diāna , Zandersone Linda , Meilerte Kristīne , Miglāne Evija , Stepens Ainars , Millers Andrejs
Published: November 2016

Objectives

To determine the validity and reliability of a Latvian version of the National Institutes of Health Stroke Scale (LV-NIHSS) for evaluating Latvian stroke patients.

Methods

The adaption of the LV-NIHSS followed standard methods used for the adaption and validation of clinical assessment tools. The scale validity was tested by comparison with the Glasgow Coma Scale (GCS) and the modified Rankin scale (mRs). The reliability of the LV-NIHSS was evaluated by intra-rater and inter-rater agreement using intra-class correlation coefficient (ICC) analysis.

Results

A total of 296 stroke patients and 101 control subjects were evaluated. The mean age of the overall study population was 73.6 years (range, 37 – 94 years; 227 [57.2%] were female). The mean LV-NIHSS score of the patients with stroke was 8.4 ± 6.2. In terms of construct validity of the LV-NIHSS, it correlated with the GCS ( r = −0.571) and mRs ( r = 0.755). In terms of the reliability of the LV-NIHSS, the inter-rater agreement had an ICC of 0.99 and the intra-rater agreement had an ICC of 0.99.

Conclusion

The adaption of LV-NIHSS was successful and the evaluation showed that the scale was valid and reliable for evaluating Latvian stroke patients.
Segmental portal/superior mesenteric vein resection and reconstruction with the iliac vein after pancreatoduodenectomy
Authors: Zhao Xin , Li Li-xin , Fan Hua , Kou Jian-tao , Li Xian-liang , Lang Ren , He Qiang
Published: November 2016

Objective

The results of segmental venous resection (VR) combined with pancreatoduodenectomy (PD) are controversial but may be promising. Few studies have described reconstruction of the portal/superior mesenteric vein (PV/SMV) with the iliac vein harvested from donation after cardiac death (DCD).

Methods

From January 2014 to April 2016, PD combined with segmental excision of the PV/SMV (VR group) was performed in 21 patients with adenocarcinoma of the head of the pancreas (ADHP). The authors established a new technique of venous reconstruction using the iliac vein from DCD and analysed patients’ long-term survival.

Results

The tumour dimensions and tumour staging were greater and the operation time was longer in the VR than PD group; however, no differences in the resection degree, blood loss, complications, reoperation rate, or mortality rate were found. The median survival was similar between the VR and PD groups. The long-term patency of the donor iliac vein was 90%. The degree of resection was a strong predictor of long-term survival.

Conclusion

Segmental PV/SMV resection combined with PD is applicable to selective patients with venous invasion by ADHP if R0 resection has probably been achieved. An iliac vein obtained by DCD provides an effective graft for venous reconstruction.
Clinical features and biological markers of lung cancer-associated stroke
Authors: Xie Xingrui , Chen Li , Zeng Jinsheng , Qin Chao , Cheng Daobin , Wei Xinxian , Liang Zhijian
Published: November 2016

Objective

To identify the unique clinical features and biological markers of lung cancer-associated stroke.

Methods

We recruited 102 patients with lung cancer plus stroke, 102 with lung cancer, and 102 with stroke. Detailed information was analysed and compared among groups.

Results

The groups were age-matched. Patients with lung cancer plus stroke showed multiple lesions involving multiple cerebral artery territories on magnetic resonance imaging, compared with stroke-alone patients. These patients also had a poorer modified Rankin Scale score at 30 days, and high mortality (18.6%). Patients with lung cancer plus stroke had a higher incidence of metastasis, and higher blood levels of D-dimer, CA125 and CA199 compared with patients with lung cancer alone. Multivariate logistic regression analysis showed that levels of D-dimer, CA125 and CA199 were independently related to lung cancer-associated stroke.

Conclusion

Elevated plasma D-dimer, CA125 and CA199 may be independent risk factors for and biomarkers of lung cancer-associated stroke.