bluuebunny/crossref_metadata_2025 huggingface dataset:
Does an emotion‐focused two‐chair dialogue add to the therapeutic effect of the empathic attunement to affect?
Authors: Stiegler Jan Reidar , Molde Helge , Schanche Elisabeth
Published: September 2017

An increasing amount of research suggests that it is beneficial to work explicitly with emotions in psychotherapy. Emotion‐focused therapy (EFT) utilizes interventions that are thought to enhance the evocativeness of emotional processing and facilitate explorations of new meaning. The purpose of this study was to examine the effect of such an intervention on therapeutic outcome. The intervention, a two‐chair dialogue drawn from emotion‐focused therapy, was added to the treatment conditions that consisted of empathically following the clients' emotional processes. The treatment comprised 2 phases. Using a multiple baseline design, 21 self‐critical clients (15 women and 6 men) with clinically significant symptoms of depression and/or anxiety first received 5, 7, or 9 sessions of a baseline treatment focused on alliance building, empathic attunement to affect, and therapeutic presence and genuineness. A two‐chair dialogue intervention was then added for 5 sessions. The symptoms were measured before each session using Beck's Depression Inventory, Beck's Anxiety Index, and Forms of Self‐Criticizing/Attacking and Self‐Reassuring Scale. An analysis using Hierarchical Linear Modelling revealed that the phase with the two‐chair dialogue had a larger impact on symptoms of anxiety and depression when compared to the baseline phase. On BDI‐II, there was a greater impact on somatic‐affective components than cognitive components. Self‐criticism was reduced when we used time as a predictor for both phases but not significantly more after introducing the intervention. The results corroborate that the two‐chair dialogue intervention is associated with change beyond what is shown when relationship conditions alone are being provided. Implications and limitations are discussed.
Variants in the CYP2B6 3′UTR Alter In Vitro and In Vivo CYP2B6 Activity: Potential Role of MicroRNAs
Authors: Burgess Kimberly S. , Ipe Joseph , Swart Marelize , Metzger Ingrid F. , Lu Jessica , Gufford Brandon T. , Thong Nancy , Desta Zeruesenay , Gaedigk Roger , Pearce Robin E. , Gaedigk Andrea , Liu Yunlong , Skaar Todd C.
Published: September 2017

CYP2B6*6 and CYP2B6*18 are the most clinically important variants causing reduced CYP2B6 protein expression and activity. However, these variants do not account for all variability in CYP2B6 activity. Emerging evidence has shown that genetic variants in the 3′UTR may explain variable drug response by altering microRNA regulation. Five 3′UTR variants were associated with significantly altered efavirenz AUC0‐48 (8‐OH‐EFV/EFV) ratios in healthy human volunteers. The rs70950385 (AG>CA) variant, predicted to create a microRNA binding site for miR‐1275, was associated with a 33% decreased CYP2B6 activity among normal metabolizers (AG/AG vs. CA/CA (P < 0.05)). In vitro luciferase assays were used to confirm that the CA on the variant allele created a microRNA binding site causing an 11.3% decrease in activity compared to the AG allele when treated with miR‐1275 (P = 0.0035). Our results show that a 3′UTR variant contributes to variability in CYP2B6 activity.
Prospects for new lung cancer treatments that target EMT signaling
Authors: Otsuki Yuji , Saya Hideyuki , Arima Yoshimi
Published: September 2017

Lung cancer is the most common cancer worldwide. Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, molecularly targeted therapy including epidermal growth factor receptor or anaplastic lymphoma kinase inhibitors, and immunotherapy. These treatments can be administered alone or in combination. Despite therapeutic advances, however, lung cancer remains the leading cause of cancer death. Recent studies have indicated that epithelial‐mesenchymal transition (EMT) is associated with malignancy in various types of cancer, and activation of EMT signaling in cancer cells is widely considered to contribute to metastasis, recurrence, or therapeutic resistance. In this review, we provide an overview of the role of EMT in the progression of lung cancer. We also discuss the prospects for new therapeutic strategies that target EMT signaling in lung cancer. Developmental Dynamics 247:462–472, 2018. © 2017 Wiley Periodicals, Inc.
A knock‐in mouse line conditionally expressing the tumor suppressor WTX/AMER1
Authors: Boutet Agnès , Comai Glenda , Charlet Aurélie , Jian Motamedi Fariba , Dhib Haroun , Bandiera Roberto , Schedl Andreas
Published: September 2017

WTX/AMER1 is an important developmental regulator, mutations in which have been identified in a proportion of patients suffering from the renal neoplasm Wilms' tumor and in the bone malformation syndrome Osteopathia Striata with Cranial Sclerosis (OSCS). Its cellular functions appear complex and the protein can be found at the membrane, within the cytoplasm and the nucleus. To understand its developmental and cellular function an allelic series for Wtx in the mouse is crucial. Whereas mice carrying a conditional knock out allele for Wtx have been previously reported, a gain‐of‐function mouse model that would allow studying the molecular, cellular and developmental role of Wtx is still missing. Here we describe the generation of a novel mouse strain that permits the conditional activation of WTX expression. Wtx fused to GFP was introduced downstream a stop cassette flanked by loxP sites into the Rosa26 locus by gene targeting. Ectopic WTX expression is reported after crosses with several Cre transgenic mice in different embryonic tissues. Further, functionality of the fusion protein was demonstrated in the context of a Wtx null allele.
Anorexia, functional capacity, and clinical outcome in patients with chronic heart failure: results from the Studies Investigating Co‐morbidities Aggravating Heart Failure (SICA‐HF)
Authors: Saitoh Masakazu , dos Santos Marcelo R. , Emami Amir , Ishida Junichi , Ebner Nicole , Valentova Miroslava , Bekfani Tarek , Sandek Anja , Lainscak Mitja , Doehner Wolfram , Anker Stefan D. , von Haehling Stephan
Published: September 2017

Aims

We aimed to assess determinants of anorexia, that is loss of appetite in patients with heart failure (HF) and aimed to further elucidate the association between anorexia, functional capacity, and outcomes in affected patients.

Methods and results

We assessed anorexia status among 166 patients with HF (25 female, 66 ± 12 years) who participated in the Studies Investigating Co‐morbidities Aggravating HF. Anorexia was assessed by a 6‐point Likert scale (ranging from 0 to 5), wherein values ≥1 indicate anorexia. Functional capacity was assessed as peak oxygen uptake (peak VO2), 6 min walk test, and short physical performance battery test. A total of 57 patients (34%) reported any anorexia, and these patients showed lower values of peak VO2, 6 min walk distance, and short physical performance battery score (all P < 0.05). Using multivariate analysis adjusting for clinically important factors, only high‐sensitivity C‐reactive protein [odds ratio (OR) 1.24, P = 0.04], use of loop diuretics (OR 5.76, P = 0.03), and the presence of cachexia (OR 2.53, P = 0.04) remained independent predictors of anorexia. A total of 22 patients (13%) died during a mean follow‐up of 22.5 ± 5.1 months. Kaplan‐Meier curves for cumulative survival showed that those patients with anorexia presented higher mortality (Log‐rank test P = 0.03).

Conclusions

Inflammation, use of loop diuretics, and cachexia are associated with an increased likelihood of anorexia in patients with HF, and patients with anorexia showed impaired functional capacity and poor outcomes.
Genetic variation of human neutrophil Fcγ receptors and SIRPα in antibody‐dependent cellular cytotoxicity towards cancer cells
Authors: Treffers Louise W. , Zhao Xi Wen , van der Heijden Joris , Nagelkerke Sietse Q. , van Rees Dieke J. , Gonzalez Patricia , Geissler Judy , Verkuijlen Paul , van Houdt Michel , de Boer Martin , Kuijpers Taco W. , van den Berg Timo K. , Matlung Hanke L.
Published: September 2017

The efficacy of cancer therapeutic antibodies varies considerably among patients. Anti‐cancer antibodies act through different mechanisms, including antibody‐dependent cellular cytotoxicity (ADCC) triggered via Fcγ receptors (FcγR). This phagocyte ADCC can be promoted by interference with CD47‐SIRPα interactions, but the magnitude of this enhancement also varies among individuals. Both FcγR and SIRPα display considerable genetic variation, and we investigated whether this explains some of the variability in ADCC. Because of linkage disequilibrium between FcγR variants the interpretation of previous reports suggesting a potential link between FcγR polymorphisms and ADCC has been troublesome. We performed an integrated genetic analysis that enables stratification. ADCC by activated human neutrophils towards Trastuzumab‐coated breast cancer cells was predominantly dependent on FcγRIIa. Neutrophils from individuals with the FcγRIIa‐131H polymorphic variant displayed significantly higher killing capacity relative to those with FcγRIIa‐131R. Furthermore, ADCC was consistently enhanced by targeting CD47‐SIRPα interactions, and there were no significant functional differences between the two most prevalent SIRPα polymorphic variants. Thus, neutrophil ADCC capacity is directly related to the FcγRIIa polymorphism, and targeting CD47‐SIRPα interactions enhances ADCC independently of FcγR and SIRPα genotype, thereby further suggesting that CD47‐SIRPα interference might be a generic strategy for potentiating the efficacy of antibody therapy in cancer.
Development of bufferless gel electrophoresis chip for easy preparation and rapid DNA separation
Authors: Oleksandrov Sergiy , Aman Abdurazak , Lim Wanyoung , Kim Younghee , Bae Nam Ho , Lee Kyoung G. , Lee Seok Jae , Park Sungsu
Published: September 2017

This work presents a handy, fast, and compact bufferless gel electrophoresis chip (BGEC), which consists of precast agarose gel confined in a disposable plastic body with electrodes. It does not require large volumes of buffer to fill reservoirs, or the process of immersing the gel in the buffer. It withstands voltages up to 28.4 V/cm, thereby allowing DNA separation within 10 min with a similar separation capability to the standard gel electrophoresis. The results suggest that our BGEC is highly suitable for in situ gel electrophoresis in forensic, epidemiological settings and crime scenes where standard gel electrophoresis equipment cannot be brought in while quick results are needed.
Dynamic buckling of braces in concentrically braced frames
Authors: Kazemzadeh Azad Sina , Topkaya Cem , Bybordiani Milad
Published: September 2017

Axially loaded members might experience compressive forces above their static buckling capacity because of dynamic buckling under rapid shortening. Although the subject is studied in the context of engineering mechanics, it has not been thoroughly investigated in the field of earthquake engineering. Such dynamic overshoots in the compressive capacity can also be observed for braces of concentrically braced frames (CBFs) during earthquakes. Consequently, a comprehensive investigation is conducted in this study regarding the effects of dynamic buckling of braces on the seismic behavior of steel CBFs. After providing a theoretical background, recent dynamic experiments on braces and CBFs are simulated and discussed to investigate the occurrence of dynamic overshoot during these tests. Eight archetype CBFs are then designed, modeled, and subjected to a large set of ground motions to provide a quantified insight on the frequency and anticipated level of dynamic overshoot in the compressive capacity of braces during earthquakes. Results of a total of 1600 nonlinear time history analyses revealed that dynamic overshoots occur frequently in braces and affect the behavior of CBFs notably. Considerable increases are recorded in forces transmitted to other members of CBFs as a consequence of such dynamic overshoots. Importance of incorporating these dynamic overshoots in the capacity design procedure of columns, beams, and gusset plates is highlighted. Furthermore, results of a parametric study are presented and summarized in the form of a simple formula that can be used as a guide for estimating the level of dynamic overshoot.
Loss of heterozygosity and uniparental disomy of chromosome region 10q23.3–26.3 in glioblastoma
Authors: Alekseeva Ekaterina A. , Kuznetsova Ekaterina B , Tanas Alexander S. , Prozorenko Evgeny V. , Zaytsev Anton M. , Kurzhupov Mikhail I , Kirsanova Olga N. , Rudenko Viktoria V. , Strelnikov Vladimir V. , Zaletaev Dmitry V.
Published: September 2017

Glioblastoma is the most frequent and aggressive brain tumor in the adult population. Loss of heterozygosity (LOH) at markers of the long arm of chromosome 10 is the most common genetic alteration in glioblastoma, being detectable in up to 80% of cases. We have tested 124 glioblastoma samples for LOH by microsatellite analysis of the 10q23.3–26.3 region which contains the cancer related genes PTEN, FGFR2, MKI67, and MGMT. Then, a real‐time quantitative microsatellite analysis (QuMA) was used to qualitatively estimate the change in copy number of this region in the samples with LOH. LOH was detected in 62.1% of the glioblastoma samples. A total of 64 samples with LOH in this region were examined by QuMA. LOH was attributed to a deletion in 37.5% of cases, and uniparental disomy (UPD) in 25% of cases. In 37.5% of cases, deletion and UPD segments alternated within the region: deletions being more frequent than UPD in its proximal part (encompassing PTEN and FGFR2) and both deletions and UPD occurring at the same frequency in its distal part (MGMT). Thus, we have investigated mechanisms of structural alterations of the chromosome region 10q23.3–26.3 in glioblastoma. In addition to a structural deletion of this region, UPD was identified as a frequent cause of LOH. We resume that more detailed studies of glioblastoma at the molecular genetic level are essential in search for potential markers suitable for predicting the disease outcome and the response to treatment.
The allocation of health (and other professional) personnel to rural areas of poor countries
Authors: Gersovitz Mark
Published: September 2017

The availability of health personnel in the rural areas of poor countries is generally seen as problematic. This paper contrasts a lottery‐based assignment of personnel between rural and urban areas to a free‐market solution in which personnel are paid a premium to accept a rural posting. The lottery system can lower total cost and increase the number of personnel in rural areas. The model benchmarked with published estimates of the premium that would be required under a free market suggests gains from the lottery could be substantial.
Does early antipsychotic response predict long‐term treatment outcome?
Authors: Rasmussen Sean A. , Rosebush Patricia I. , Mazurek Michael F.
Published: September 2017

Objective

Early antipsychotic response within the first 2–3 weeks of treatment can predict short‐term outcomes after several months. We conducted the current study to determine whether the predictive value of early antipsychotic response persists throughout long‐term treatment over multiple years.

Methods

In this observational study, we conducted follow‐up assessments of 64 patients with first‐episode psychosis an average of 25 months after they began antipsychotic treatment. Patients were initially randomized to receive haloperidol or olanzapine, but treatment after the acute hospitalization period was not controlled. Regression analyses were used to determine whether early improvement on the Brief Psychiatric Rating Scale at 2 or 3 weeks predicted longer term improvement at follow‐up. We conducted secondary analyses to determine whether early response could predict extrapyramidal side effects at follow‐up.

Results

Early response to haloperidol at 2 weeks predicted Brief Psychiatric Rating Scale improvement on longer term follow‐up (p = .002). Longer term improvement was not predicted by early response to olanzapine at 2 weeks (p = .726) or 3 weeks (p = .541). Rates of extrapyramidal side effects did not differ between treatment groups and were not predicted by early response.

Conclusion

These results demonstrate the long‐term prognostic value of early haloperidol response. The predictive value of early olanzapine response may be less robust.
Testing the maximum entropy production approach for estimating evapotranspiration from closed canopy shrubland in a low‐energy humid environment
Authors: Wang Hailong , Tetzlaff Doerthe , Soulsby Chris
Published: September 2017

Quantifying and partitioning evapotranspiration (ET) into evaporation and transpiration is challenging but important for interpreting vegetation effects on the water balance. We applied a model based on the theory of maximum entropy production to estimate ET for shrubs for the first time in a low‐energy humid headwater catchment in the Scottish Highlands. In total, 53% of rainfall over the growing season was returned to the atmosphere through ET (59 ± 2% as transpiration), with 22% of rainfall ascribed to interception loss and understory ET. The remainder of rainfall percolated below the rooting zone. The maximum entropy production model showed good capability for total ET estimation, in addition to providing a first approximation for distinguishing evaporation and transpiration in such ecosystems. This study shows that this simple and low‐cost approach has potential for local to regional ET estimation with availability of high‐resolution hydroclimatic data. Limitations of the approach are also discussed.
IL‐12 and IL‐15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells
Authors: Hydes Theresa , Noll Angela , Salinas‐Riester Gabriela , Abuhilal Mohammed , Armstrong Thomas , Hamady Zaed , Primrose John , Takhar Arjun , Walter Lutz , Khakoo Salim I.
Published: September 2017

Introduction

Murine hepatic NK cells exhibit adaptive features, with liver‐specific adhesion molecules CXCR6 and CD49a acting as surface markers.

Methods

We investigated human liver‐resident CXCR6+ and CD49a+ NK cells using RNA sequencing, flow cytometry, and functional analysis. We further assessed the role of cytokines in generating NK cells with these phenotypes from the peripheral blood.

Results

Hepatic CD49a+ NK cells could be induced using cytokines and produce high quantities of IFNγ and TNFα, in contrast to hepatic CXCR6+ NK cells. RNA sequencing of liver‐resident CXCR6+ NK cells confirmed a tolerant immature phenotype with reduced expression of markers associated with maturity and cytotoxicity. Liver‐resident double‐positive CXCR6 + CD49a+ hepatic NK cells are immature but maintain high expression of Th1 cytokines as observed for single‐positive CD49a+ NK cells. We show that stimulation with activating cytokines can readily induce upregulation of both CD49a and CXCR6 on NK cells in the peripheral blood. In particular, IL‐12 and IL‐15 can generate CXCR6 + CD49a+ NK cells in vitro from NK cells isolated from the peripheral blood, with comparable phenotypic and functional features to liver‐resident CD49a+ NK cells, including enhanced IFNγ and NKG2C expression.

Conclusion

IL‐12 and IL‐15 may be key for generating NK cells with a tissue‐homing phenotype and strong Th1 cytokine profile in the blood, and links peripheral activation of NK cells with tissue‐homing. These findings may have important therapeutic implications for immunotherapy of chronic liver disease.
Novel targets for sensitizing breast cancer cells to TRAIL‐induced apoptosis with siRNA delivery
Authors: Thapa Bindu , Bahadur KC Remant , Uludağ Hasan
Published: September 2017

Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) induces apoptosis in variety of cancer cells without affecting most normal cells, which makes it a promising agent for cancer therapy. However, TRAIL therapy is clinically not effective due to resistance induction. To identify novel regulators of TRAIL that can aid in therapy, protein targets whose silencing sensitized breast cancer cells against TRAIL were screened with an siRNA library against 446 human apoptosis‐related proteins in MDA‐231 cells. Using a cationic lipopolymer (PEI‐αLA) for delivery of library members, 16 siRNAs were identified that sensitized the TRAIL‐induced death in MDA‐231 cells. The siRNAs targeting BCL2L12 and SOD1 were further evaluated based on the novelty and their ability to sensitize TRAIL induced cell death. Silencing both targets sensitized TRAIL‐mediated cell death in MDA‐231 cells as well as TRAIL resistant breast cancer cells, MCF‐7. Combination of TRAIL and siRNA silencing BCL2L12 had no effect in normal human umbilical vein cells and human bone marrow stromal cell. The silencing of BCL2L12 and SOD1 enhanced TRAIL‐mediated apoptosis in MDA‐231 cells via synergistically activating capsase‐3 activity. Hence, here we report siRNAs targeting BCL2L12 and SOD1 as a novel regulator of TRAIL‐induced cell death in breast cancer cells, providing a new approach for enhancing TRAIL therapy for breast cancer. The combination of siRNA targeting BCL2L12 and TRAIL can be a highly effective synergistic pair in breast cancer cells with minimal effect on the non‐transformed cells.
Serum Calcium to Phosphorous (Ca/P) Ratio Is a Simple, Inexpensive, and Accurate Tool in the Diagnosis of Primary Hyperparathyroidism
Authors: Madeo Bruno , Kara Elda , Cioni Katia , Vezzani Silvia , Trenti Tommaso , Santi Daniele , Simoni Manuela , Rochira Vincenzo
Published: September 2017

Primary hyperparathyroidism (PHPT) diagnosis is challenging and is based on serum calcium (Ca) and parathyroid hormone (PTH). Because serum Ca and phosphorous (P) are inversely related in PHPT, we investigated the diagnostic value of the serum Ca/P ratio in the diagnosis of PHPT. We report a single‐center, case‐controlled, retrospective study including 97 patients with documented PHPT and compared them with those of 96 controls (C). The main outcome measures were: serum PTH, 25‐OH vitamin D, Ca, P, albumin, and creatinine. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the serum Ca/P ratio were calculated. The results were verified using an independent, anonymous set of data extracted from a laboratory database containing over 900 million entries. A total of 35 (36.1%) PHPT patients had normocalcemic PHPT (NCHPT). Ca and PTH were significantly higher in PHPT than in C (p < 0.0001). P was significantly lower in PHPT than in C (p < 0.0001). The Ca/P ratio was significantly higher in PHPT than in C (p < 0.0001). Receiver‐operating characteristic (ROC) curves analyses identified a cutoff of 2.71 (3.5 if Ca and P are expressed in mg/dL) for Ca/P ratio with a sensitivity and specificity of 86% and 87%, respectively (p < 0.0001), confirmed by the independent, big data approach. In conclusion, Ca/P is a valuable tool for the diagnosis of PHPT and is of superior value compared to serum Ca alone, especially in NCPHT. Because Ca/P is simple, inexpensive, and easily accessible worldwide, this ratio is useful for PHPT diagnosis, especially in laboratory/medical settings relying on limited resources, such as low‐income countries. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Primary Osteoporosis in Young Adults: Genetic Basis and Identification of Novel Variants in Causal Genes
Authors: Collet Corinne , Ostertag Agnès , Ricquebourg Manon , Delecourt Marine , Tueur Giulia , Isidor Bertrand , Guillot Pascale , Schaefer Elise , Javier Rose‐Marie , Funck‐Brentano Thomas , Orcel Philippe , Laplanche Jean‐Louis , Cohen‐Solal Martine
Published: September 2017

Genetic determinants contribute to osteoporosis and enhance the risk of fracture. Genomewide association studies of unselected population‐based individuals or families have identified polymorphisms in several genes related to low bone density, but not in osteoporotic patients with Z‐score < −2.0 SD with fragility fracture(s). The aim of this study was to determine the causal genes of idiopathic osteoporosis in the adulthood. Also, we used next‐generation sequencing of candidate genes in a cohort of 123 young or middle‐aged adults with idiopathic osteoporosis. All patients were included if they had a low bone mineral density (Z‐score < −2 SD), a diagnosis before age 55 years (mean ± SD, 48.4 ± 10.6 years; mean ± SD age at first fracture, 30.4 ± 17.4 years) and fracture or not. We found that 11 patients carried rare or novel variants in COL1A2 (n = 4), PLS3 (n = 2), WNT1 (n = 4), or DKK1 (n = 1). We showed a high prevalence of pathogenic variants in LRP5: 22 patients (17.8%) had the p.Val667Met variant, including three at the homozygous level and 16 (13%) carrying a novel or very rare variant. Functional analysis revealed that the LRP5 missense variants resulted in reduced luciferase activity, which indicates reduced activation of canonical WNT signaling. The clinical phenotype of patients carrying causal gene variants was indistinguishable. In conclusion, molecular screening of young osteoporotic adults revealed several variants and could be useful to characterize susceptibility genes for personalizing treatment, in particular for the new anabolic drugs.© 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Prediction of seebeck coefficient for compounds without restriction to fixed stoichiometry: A machine learning approach
Authors: Furmanchuk Al'ona , Saal James E. , Doak Jeff W. , Olson Gregory B. , Choudhary Alok , Agrawal Ankit
Published: September 2017

The regression model‐based tool is developed for predicting the Seebeck coefficient of crystalline materials in the temperature range from 300 K to 1000 K. The tool accounts for the single crystal versus polycrystalline nature of the compound, the production method, and properties of the constituent elements in the chemical formula. We introduce new descriptive features of crystalline materials relevant for the prediction the Seebeck coefficient. To address off‐stoichiometry in materials, the predictive tool is trained on a mix of stoichiometric and nonstoichiometric materials. The tool is implemented into a web application (http://info.eecs.northwestern.edu/SeebeckCoefficientPredictor) to assist field scientists in the discovery of novel thermoelectric materials. © 2017 Wiley Periodicals, Inc.
Lightning activity associated with precipitation and CAPE over Bangladesh
Authors: Dewan Ashraf , Ongee Emmanuel T. , Rafiuddin M. , Rahman Md. Masudur , Mahmood Rezaul
Published: September 2017

Satellite‐derived lightning data for 17 years (1998–2014) were used to evaluate the relation between environmental factors and lightning activity over the Bangladesh landmass. Time series convective available potential energy (CAPE) data were extracted from ERA‐40 reanalysis data while total and convective rainfalls were obtained from Tropical Rainfall Measuring Mission's monthly products. In addition, the product of CAPE and precipitation was computed and used as an additional variable. Three timescales – monthly, seasonal and annual – were utilized to determine the influence of precipitation and CAPE on lightning activity. The results indicated that CAPE stands out as an important variable at all of these timescales for predicting the occurrence of lightning. The correlation coefficient (r) between CAPE and lightning activity was found to be 0.902 (monthly), 0.703 (pre‐monsoon), 0.550 (monsoon) and 0.702 (annual), respectively. Total rain showed strong positive correlation with lightning on monthly scale (r = 0.734) and in the pre‐monsoon season (r = 0.701). However, such relationship was moderate during monsoon (r = 0.455). In contrast, convective rain showed slightly higher correlation during monsoon (r = 0.587) compared with that of pre‐monsoon season (r = 0.532). Because of strong seasonality in the data, convective rain did not exhibit strong relationship on annual scale (r = 0.227). The product variable (e.g. CAPE × precipitation) showed significant correlation on monthly (r = 0.895) and seasonal scales (r = 0.818 during pre‐monsoon and 0.686 in monsoon) but its influence appears to diminish on a longer timescale (r = 0.375). Spatial maps of correlation coefficient revealed significant positive correlation along relatively drier northern parts of Bangladesh. As lightning‐related fatality is on the rise, this study, first of its kind, is expected to inform public policy and provide information necessary for effective management of this atmospheric phenomenon to save lives and property in Bangladesh.
A validated LC–MS/MS method for the simultaneous determination of 20‐(S)‐protopanaxatriol and its two active metabolites in rat plasma: Application to a pharmacokinetics study
Authors: Qiu Xin , Yang Jiali , Wang Wei , Wu Qiuhong , Shao Hong
Published: September 2017

We present a validated liquid chromatography with tandem mass spectrometry method for simultaneous determination of 20‐(S)‐protopanaxatriol and its two oxidative stereoisomeric metabolites (20S,24S)‐epoxy‐dammarane‐3,6,12,25‐tetraol (M1) and (20S,24R)‐epoxy‐dammarane‐3,6,12,25‐tetraol (M2) in rat plasma. 20‐(S)‐Protopanaxatriol, M1, and M2 were extracted with methanol and separated on an ACQUITY HSS T3 column. The mass spectrometry detection was accomplished in selected reaction monitoring mode with precursor‐to‐product ion transitions of m/z 493.4→143.1 for M1 and M2, m/z 475.4→391.3 for 20‐(S)‐protopanaxatriol, and m/z 459.4→375.3 for 20‐(S)‐protopanaxadiol (internal standard). The method showed good linearity over the concentration ranges of 1–1000 ng/mL for 20‐(S)‐protopanaxatriol and 0.5–200 ng/mL for M1 and M2, with correlation coefficients of more than 0.995. The lower limits of quantification for 20‐(S)‐protopanaxatriol, M1, and M2 were 1, 0.5, 0.5 ng/mL, respectively. The intra‐ and interday precisions (RSD, %) were less than 10.41% while the accuracy (relative error, %) ranged from –3.14 to 8.73%. Under the current conditions, M1 and M2 were completely separated within 3 min. The validated assay was successfully applied to evaluating pharmacokinetic profiles of 20‐(S)‐protopanaxatriol, M1, and M2 in rat.
Teenage Onset Head Tremor Due to Novel Mutation in GNAL Gene
Authors: O'Connor Antoinette , Buckley Mary , O'Sullivan Sean S.
Published: September 2017

View Supplementary Video 1
Lymphatic mapping of the upper limb with lymphedema before lymphatic supermicrosurgery by mirroring of the healthy limb
Authors: Gentileschi Stefano , Servillo Maria , Albanese Roberta , De Bonis Francesca , Tartaglione Girolamo , Salgarello Marzia
Published: September 2017

Introduction

Supermicrosurgical lymphatic‐venous anastomosis (LVA) can improve limbs lymphedema. We describe a technique that we employ for preoperative lymphatic mapping of the upper limb (UL), when indocyanine green (ICG) lymphography shows only dermal backflow (DB) and no lymphatic vessel is detectable.

Patients and methods

Sixteen patients undergoing LVA for unilateral UL lymphedema, showing “stardust” or “diffuse” DB pattern, were included. Demographic, clinical data, and limbs measurements were recorded. LymQoL arm questionnaire was administered. Mean age of patients was 58.8 ± 13.1 years. Fifteen were females and 1 male. Lymphatic anatomy of the healthy limb was investigated by ICG lymphography and reported on the affected limb by a four steps technique: marking the main lymphatic pathway on the healthy limb, measuring of the distances at seven levels between the pathway and a line joining fixed landmarks, reporting these measurements on the affected limb with a correction proportional to the degree of swelling, marking skin incisions at the intersection of this pathway with venules, individuated by near infrared light system. Results were analyzed by postoperative questionnaire and changes of limb measurements.

Results

For every limb, we could find 3 ± 0.73 incision sites each containing at least one lymphatic vessel suitable for anastomosis. In every patient, we could perform 3.38 ± 0.62 anastomoses. Mean follow‐up was 12.13 ± 2.73 months. After surgery, mean preoperative QoL score increased from 5.5 to 7.9 (P < .001), and mean difference between the mean circumferences of the affected and healthy limbs decreased from 4.3 ± 1.3 to 2.5 ± 1.3 cm, showing improvement of swelling after surgery (P < .01).

Conclusion

This technique allowed to preoperatively map UL lymphatics even if diffuse DB was present.
Feature preserving multiresolution subdivision and simplification of point clouds: A conformal geometric algebra approach
Authors: Yuan Shuai , Zhu Shuai , Li Dong‐Shuang , Luo Wen , Yu Zhao‐Yuan , Yuan Lin‐Wang
Published: September 2017

Due to the huge volume and complex structure, simplification of point clouds is an important technique in practical applications. However, the traditional algorithms often lose geometric information and have no dynamic expanding structure. In this paper, a new simplification algorithm is proposed based on conformal geometric algebra. First of all, a multiresolution subdivision is constructed by the sphere tree, which computes the minimal bounding spheres with the help of k‐means clustering, and then 2 kinds of simplification methods with full advantages of distance computing convenience are applied to carry out self‐adapting simplification. Finally, several comparisons with original data or other algorithms are implemented from visualization to parameter contrast. The results show that the proposed algorithm has good effect not only on the local details but also on the overall error rate.
Beetroot and Sodium Nitrate Ameliorate Cardiometabolic Changes in Diet‐Induced Obese Hypertensive Rats
Authors: Bhaswant Maharshi , Brown Lindsay , McAinch Andrew J. , Mathai Michael L.
Published: September 2017

Scope

Dietary intake of beetroot by humans reduces blood pressure but whether this is caused by nitrate or betanin is not well‐defined; neither are effects on other signs of metabolic syndrome.

Methods and results

Rats fed a high‐carbohydrate, high‐fat diet (H) for 16 weeks developed abdominal obesity, hypertension, altered cardiovascular and liver structure and function, and impaired glucose tolerance compared to rats fed a corn starch diet (C). H rats treated with ∼16 mg/kg/day of nitrate either from beetroot juice (H+B) or sodium nitrate (H+N) for the last 8 weeks reduced systolic blood pressure by ∼25 mmHg, improved cardiac structure and function, plasma lipid profile and plasma markers of liver function, reduced inflammatory cell infiltration in heart and liver and decreased left ventricular fibrosis. In the left ventricle, H rats increased mRNA expression of connective tissue growth factor (CTGF), monocyte chemoattractant protein 1 (MCP‐1), matrix metalloproteinase‐2 (MMP‐2), and adenosine monophosphate‐activated protein kinase‐alpha (AMPK‐α) and decreased mRNA expression of peroxisome proliferator‐activated receptor‐alpha (PPAR‐α); both beetroot and sodium nitrate diet‐fed rats decreased CTGF threefold, MCP‐1, and MMP‐2 twofold, and doubled PPAR‐α mRNA expression in left ventricular tissue.

Conclusion

The similar functional and molecular responses to beetroot and sodium nitrate indicate that the nitrate content of beetroot reduced inflammation and improved cardiovascular, liver, and metabolic function in rats with metabolic syndrome, rather than betanin.
Similarity solution for cavity expansion in thermoplastic soil
Authors: Zhou Hang , Kong Gangqiang , Liu Hanlong , Laloui Lyesse
Published: September 2017

This paper presents an analytical solution for cavity expansion in thermoplastic soil considering non‐isothermal conditions. The constitutive relationship of thermoplasticity is described by Laloui's advanced and unified constitutive model for environmental geomechanical thermal effect (ACMEG‐T), which is based on multi‐mechanism plasticity and bounding surface theory. The problem is formulated by incorporating ACMEG‐T into the theoretical framework of cavity expansion, yielding a series of partial differential equations (PDEs). Subsequently, the PDEs are transformed into a system of first‐order ordinary differential equations (ODEs) using a similarity solution technique. Solutions to the response parameters of cavity expansion (stress, excess pore pressure, and displacement) can then be obtained by solving the ODEs numerically using mathematical software. The results suggest that soil temperature has a significant influence on the pressure‐expansion relationships and distributions of stress and excess pore pressure around the cavity wall. The proposed solution quantifies the influence of temperature on cavity expansion for the first time and provides a theoretical framework for predicting thermoplastic soil behavior around the cavity wall. The solution found in this paper can be used as a theoretical tool that can potentially be employed in geotechnical engineering problems, such as thermal cone penetration tests, and nuclear waste disposal problems.
Quasi‐HSS iteration methods for non‐Hermitian positive definite linear systems of strong skew‐Hermitian parts
Authors: Bai Zhong‐Zhi
Published: September 2017

For large sparse non‐Hermitian positive definite linear systems, we establish exact and inexact quasi‐HSS iteration methods and discuss their convergence properties. Numerical experiments show that both iteration methods are effective and robust when they are used either as linear solvers or as matrix splitting preconditioners for the Krylov subspace iteration methods. In addition, these two iteration methods are, respectively, much more powerful than the exact and inexact HSS iteration methods, especially when the linear systems have nearly singular Hermitian parts or strongly dominant skew‐Hermitian parts, and they can be employed to solve non‐Hermitian indefinite linear systems with only mild indefiniteness.
Vulnerabilities in Lagrange‐based distributed model predictive control
Authors: Velarde Pablo , Maestre José M. , Ishii Hideaki , Negenborn Rudy R.
Published: September 2017

In this paper, we present an analysis of the vulnerability of a distributed model predictive control scheme. A distributed system can be easily attacked by a malicious agent that modifies the reliable information exchange. We consider different types of so‐called insider attacks. In particular, we analyze a controller that is part of the control architecture that sends false information to others to manipulate costs for its own advantage. We propose a mechanism to protect or, at least, relieve the consequences of the attack in a typical distributed model predictive control negotiation procedure. More specifically, a consensus approach that dismisses the extreme control actions is presented as a way to protect the distributed system from potential threats. Two applications are considered as case studies, ie, an academic example involving the control of a distributed system with a single coupled input and a distributed local electricity grid of households. The results are presented via simulations to illustrate both the consequences of the attacks and the defense mechanisms.
Intraobserver and interobserver reproducibility of third trimester uterine artery pulsatility index
Authors: Marchi Laura , Gaini Claudia , Franchi Chiara , Mecacci Federico , Bilardo Caterina , Pasquini Lucia
Published: September 2017

Objectives

The primary aim of the study was to investigate intraobserver and interobserver reproducibility of uterine artery (UtA) pulsatility index (PI) in the third trimester of pregnancy. The secondary aim of the study was to examine whether high maternal body mass index (BMI) or gestational age (GA) influence the reliability of this measurement.

Methods

Singleton pregnancies in women with known BMI were recruited between 30+0 and 40+0 weeks. UtA PI Doppler measurements were performed prospectively, independently, and blindly by 2 Fetal Medicine Foundation–accredited operators. Intraobserver and interobserver reproducibility was assessed by concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC); Bland‐Altman plots were built and limits of agreement (LoA) were calculated. The analysis was performed for both raw numbers and percentiles. To estimate the intraoperator and interoperator agreement in defining normal and pathological measurements, the assessments were divided in 2 categories—UtA PI <95th percentile/ ≥95th percentile—and Cohen's kappa coefficients were calculated. Results were interpreted according to the cutoffs reported by the True Reproducibility of Ultrasound Techniques review. Correlation between maternal BMI and GA and accuracy of UtA measurements was studied with Spearman's correlation coefficient.

Results

Measurements were available in 101 women. For intraobserver reproducibility, ICCs and CCCs were calculated for raw values and percentiles and were 0.912 and 0.835, and 0.837 and 0.716, respectively. For interobserver reproducibility, ICCs and CCCs were 0.809 and 0.732, and 0.677 and 0.576, respectively. This indicates a poor‐moderate reproducibility of third trimester UtA PI. LoA were also wide (from a minimum of −0.30‐0.35 to a maximum of −0.53‐0.62). Cohen's kappa coefficients were 0.478 and 0.418, showing a moderate intraoperator and interoperator agreement in distinguishing between normal and pathological values. No correlation was found between maternal BMI and GA and reproducibility of the measurements.

Conclusions

Intraobserver and interobserver reproducibility of third trimester UtA PI as assessed by ICC, CCC, and LoA is only moderate‐poor. The agreement between operators in defining pathological and normal measurements is moderate.
Thrombotic risk minimization for Diane‐35 and generics
Authors: Bezemer Irene D. , Smits Elisabeth , Penning‐van Beest Fernie J.A. , Asiimwe Alex , Herings Ron M.C.
Published: September 2017

Background

This study aimed to evaluate the effect of risk minimization measures on cyproterone acetate/ethinylestradiol (CPA/EE) use in the Netherlands. Potential indications of use and concomitant pharmacy dispensing of other hormonal contraceptives (HC) were assessed among new users in 2011, 2012, and 2014.

Methods

In this retrospective drug utilization study, new CPA/EE users were identified by pharmacy dispensings in the PHARMO Database Network in 2011, 2012, and 2014. Recent dispensing of drugs to treat acne and concomitant dispensing of other HC were also assessed. General practitioner records were linked to identify diagnoses of acne, other hyperandrogenic conditions, menstrual problems, or consultations for contraceptive management in the preceding year.

Results

The number of new CPA/EE users identified per year was 7876 in 2011 and 7562 in 2012 (3.7 new users per 1000 women in both years) and 1401 in 2014 (0.7 per 1000 women). The proportions of users with acne diagnosis or treatment were 55% in 2011, 52% in 2012, and 47% in 2014. Concomitant use of other HC was observed for 3% of new CPA/EE users in 2011, and 2% in 2012 and 2014 (median duration 78 days). Another 25% were potential concomitant users (median duration 60 days).

Conclusion

This descriptive analysis showed similar proportions of CPA/EE users examined with acne or other hyperandrogenic conditions, or with recent acne treatment, or concomitant dispensing of other HC in the Netherlands before and after the referral procedure. The key observation was a strong overall reduction of CPA/EE use in the Netherlands.
Patient information in phase 1 trials: A systematic review
Authors: Gad Katrine Toubro , Lassen Ulrik , Mau‐Søerensen Morten , Høybye Mette Terp , Johansen Christoffer
Published: September 2017

Objective

To review what is known about cancer patients' decisions to enter a phase 1 trial and how they and their relatives perceive the information they receive when they are invited to participate.

Methods

This systematic review is based on the principles of “preferred reporting items for systematic reviews and meta‐analyses.” A systematic search was performed in the PubMed, Embase, and PsycInfo databases, supplemented by a search for unpublished literature.

Results

We identified 37 studies for inclusion in this review. Patients' decisions to participate in a phase 1 trial were influenced by the drug being tested, information procedures, physician‐related factors, and the patient's individual approach to decision making. Patients have difficulties correctly repeating the purpose of a phase 1 trial. In several studies, most patients expressed expectations of personal benefit from participating. Studies performing analyses of the dialog demonstrated that the language of the physicians was incomplete. The relatives' perceptions of such information remain unexplored. Most studies had a comprehensive risk of bias.

Conclusions

Patients' decisions regarding participation in phase 1 trials are based on more than the information of the trial. The way patients express the information they have been given could be limited by the applied methods for evaluating this variable. While relatives are expected to be resources for patients entering a phase 1 trial, this topic has not been investigated.
Time‐between‐events control charts for an exponentiated class of distributions of the renewal process
Authors: Ali Sajid
Published: September 2017

Time‐between‐events control charts are commonly used to monitor high‐quality processes and have several advantages over the ordinary control charts. In this article, we present some new control charts based on the renewal process, where a class of absolutely continuous exponentiated distributions is assumed for the time between events. This class includes the generalized exponential, generalized Rayleigh, and exponentiated Pareto distributions. Although we discuss the design structure for all the mentioned distributions, our main focus will be on the generalized exponential distribution due to its practical relevance and popularity. Since the generalized exponential distribution is a generalization of the traditional exponential distribution, the new control chart is more flexible than the existing exponential time‐between‐events charts. The control chart performance is evaluated in terms of some useful measures, including the average run length (ARL), the expected quadratic loss, continuous ranked probability, and the relative ARL. The effect of parameter estimation using the maximum likelihood and Bayesian methods on the ARL is also discussed in this article. The study also presents an illustrative example and 4 case studies to highlight the practical relevance of the proposal.