bluuebunny/crossref_metadata_2025 huggingface dataset:
Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti‐androgens
Authors: Ylitalo Erik Bovinder , Thysell Elin , Thellenberg‐Karlsson Camilla , Lundholm Marie , Widmark Anders , Bergh Anders , Josefsson Andreas , Brattsand Maria , Wikström Pernilla
Published: December 2019

Background

Taxane treatment may be a suitable therapeutic option for patients with castration‐resistant prostate cancer and high expression of constitutively active androgen receptor variants (AR‐Vs). The aim of the study was to compare the effects of cabazitaxel and androgen deprivation treatments in a prostate tumor xenograft model expressing high levels of constitutively active AR‐V7. Furthermore, mechanisms behind acquired cabazitaxel resistance were explored.

Methods

Mice were subcutaneously inoculated with 22Rv1 cells and treated with surgical castration (n = 7), abiraterone (n = 9), cabazitaxel (n = 6), castration plus abiraterone (n = 8), castration plus cabazitaxel (n = 11), or vehicle and/or sham operation (n = 23). Tumor growth was followed for about 2 months or to a volume of approximately 1000 mm3. Two cabazitaxel resistant cell lines; 22Rv1‐CabR1 and 22Rv1‐CabR2, were established from xenografts relapsing during cabazitaxel treatment. Differential gene expression between the cabazitaxel resistant and control 22Rv1 cells was examined by whole‐genome expression array analysis followed by immunoblotting, immunohistochemistry, and functional pathway analysis.

Results

Abiraterone treatment alone or in combination with surgical castration had no major effect on 22Rv1 tumor growth, while cabazitaxel significantly delayed and in some cases totally abolished 22Rv1 tumor growth on its own and in combination with surgical castration. The cabazitaxel resistant cell lines; 22Rv1‐CabR1 and 22Rv1‐CabR2, both showed upregulation of the ATP‐binding cassette sub‐family B member 1 (ABCB1) efflux pump. Treatment with ABCB1 inhibitor elacridar completely restored susceptibility to cabazitaxel, while treatment with AR‐antagonists bicalutamide and enzalutamide partly restored susceptibility to cabazitaxel in both cell lines. The cholesterol biosynthesis pathway was induced in the 22Rv1‐CabR2 cell line, which was confirmed by reduced sensitivity to simvastatin treatment.

Conclusions

Cabazitaxel efficiently inhibits prostate cancer growth despite the high expression of constitutively active AR‐V7. Acquired cabazitaxel resistance involving overexpression of efflux transporter ABCB1 can be reverted by bicalutamide or enzalutamide treatment, indicating the great clinical potential for combined treatment with cabazitaxel and anti‐androgens.
Investigation and Evaluation of Pyroelectric Materials for Thermal Energy Harvesting
Authors: Siao An-Shen , Hsiao Chun-Ching , Chao Ching-Kong
Published: December 2019

A simplified thermodynamics‐based model on pyroelectricity is used to estimate the sample transient temperature fields, electrical outputs, and induced thermal stresses during pyroelectric energy conversion. A numerical analysis presents an optimal saturated voltage of 73.0 V for a 4.7 μF capacitor obtained by a 0.1 mm‐thick disk pyroelectric cell under an input heat flux of 10 000 W m−2 and an applied forced convection of 50 W m−2 K−1 at 0.06 Hz to prevent the sample from undergoing phase transition due to high temperature. Thermal stress analysis shows that the maximum strain energy density occurs near the edge of the cell, and it increases with increasing thermal convection coefficient. Moreover, it is observed that a thinner sample possesses a lower thermal capacitance and an excellent pyroelectric response. However, this may lead to a higher temperature gradient near the edge region during the cooling process at a lower frequency and put the sample at a higher risk of damage.
Simple and sensitive method for the analysis of 14 antituberculosis drugs using liquid chromatography/tandem mass spectrometry in human plasma
Authors: Lei Qian , Zhao Yuan , Wang Hao , Zhou Jun , Lv Xiaohui , Dang Liyun , Zhu Changsheng
Published: December 2019

Rationale

Monitoring plasma concentration and adjusting doses of antituberculosis (TB) drugs are beneficial for improving responses to drug treatment and avoiding adverse drug reactions. A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed to measure the plasma concentrations of 14 anti‐TB drugs: ethambutol, isoniazid, pyrazinamide, levofloxacin, gatifloxacin, moxifloxacin, prothionamide, linezolid, rifampin, rifapentine, rifabutin, cycloserine, p‐aminosalicylic acid, and clofazimine.

Methods

Human plasma was precipitated by acetonitrile and was subsequently separated by an AQ‐C18 column with a gradient elution. Drug concentrations were determined using multiple reaction monitoring in positive ion electrospray ionization mode. According to pharmacokinetic data of patients, the peak concentration ranges and the timing of blood collection were determined.

Results

Intra‐ and interday precision was < 14.8%. Linearity, accuracy, extraction recovery, and matrix effect were acceptable for each drug. The stability of the method satisfied different storage conditions.

Conclusions

The method allowed the sensitive and reproducible determination of 14 frequently used anti‐TB drugs which has already been of benefit for some TB patients.
Robust formation control of multiagent systems on the Lie group SE(3)
Authors: Ghasemi Kobra , Ghaisari Jafar , Abdollahi Farzaneh
Published: December 2019

This paper addresses the robust formation control problem of multiple rigid bodies whose kinematics and dynamics evolve on the Lie group SE(3). First, it is assumed that all followers have access to the state information of a virtual leader. Then, a novel adaptive super‐twisting sliding mode control with an intrinsic proportional‐integral‐derivative sliding surface is proposed for the formation control problem of multiagent system using a virtual structure (VS) approach. The advantages of this control scheme are twofold: elimination of the chattering phenomenon without affecting the control performance and no requirement of prior knowledge about the upper bound of uncertainty/disturbance due to adaptive‐tuning law. Since the VS method is suffering from the disadvantages of centralized control, in the second step, considering a network as an undirected connected graph, we assume that only a few agents have access to the state information of the leader. Afterward, using the gradient of modified error function, a distributed adaptive velocity‐free consensus‐based formation control law is proposed where reduced‐order observers are introduced to remove the requirements of velocity measurements. Furthermore, to relax the requirement that all agents have access to the states of the leader, a distributed finite‐time super‐twisting sliding mode estimator is proposed to obtain an accurate estimation of the leader's states in a finite time for each agent. In both steps, the proposed control schemes are directly developed on the Lie group SE(3) to avoid singularity and ambiguities associated with the attitude representations. Numerical simulation results illustrated the effectiveness of the proposed control schemes.
Solving university course timetabling problem using localized island model genetic algorithm with dual dynamic migration policy
Authors: Gozali Alfian A. , Kurniawan Bobby , Weng Wei , Fujimura Shigeru
Published: December 2019

The University Course Timetabling Problem (UCTP) is a scheduling problem of assigning a teaching event in a certain time and room by considering the constraints of university stakeholders such as students, lecturers, and departments. This problem becomes complicated for universities with a large number of students and lecturers. Moreover, several universities are implementing student sectioning, which is a problem of assigning students to classes of a subject while respecting individual student requests, along with additional constraints. Such implementation also implies the complexity of constraints, which is larger accordingly. However, current and generic solvers have failed to meet the scalability and reliability requirements for student sectioning UCTP. In this paper, we introduce the localized island model genetic algorithm with dual dynamic migration policy (DM‐LIMGA) to solve student sectioning UCTP. Our research shows that DM‐LIMGA can produce a feasible timetable for the student sectioning problem and get better results than previous works and the current UCTP solver. Our proposed solution also consistently yield lower violation number than other algorithms, as evidenced by UCTP benchmark experiment results. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Distributed day‐ahead scheduling of community energy management system group considering uncertain market prices using stochastic optimization
Authors: Miyamoto Toshiyuki , Kitamura Shoichi , Naito Kento , Mori Kazuyuki , Izui Yoshio
Published: December 2019

Because of the deregulation of electric power, electricity supply has changed from an exclusive supply by general electric utilities in each region to a competitive supply by various electric utilities. Furthermore, the wholesale electric power exchange (EPX) has been established, and it is becoming possible to procure and sell electricity through the market. Because the prices in the EPX are uncertain, a planning method considering the uncertainty is needed. A community energy management system (CEMS) stands between energy consumers in the community and energy suppliers. A CEMS purchases energy from external power supply sources and operates the equipment to provide ancillary service to consumers. In this paper, we consider the day‐ahead scheduling problem of a CEMS group using stochastic optimization. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Enhancement of Photostabilization of Poly(vinyl chloride) Doped with Sulfadiazine Tin Complexes
Authors: Ahmed Dina S. , El‐Hiti Gamal A. , Ibraheem Hanan , Alotaibi Mohammad Hayal , Abdallh Mustafa , Ahmed Ahmed A. , Ismael Mustafa , Yousif Emad
Published: December 2019

New sulfadiazine tin complexes were synthesized in 67–80% yields from the reaction of sulfadiazine, and different organotin(IV) chlorides and their structures were established. The synthesized complexes were used as additives at a low concentration (0.5% by weight) to enhance poly(vinyl chloride) (PVC) photostability. The PVC samples containing sulfadiazine tin complexes (thickness = 40 μm) were fabricated and irradiated with ultraviolet light at room temperature for 300 h. The changes that occurred within the PVC samples upon irradiation were investigated by inspecting the loss in weight, reduction in the average molecular weight, formation of small degradation fragments containing polyene, carbonyl, and hydroxyl moieties, and changes in the ultraviolet absorption intensity of polymeric materials. The surface morphology of irradiated PVC samples was investigated using optical, atomic force, and scanning electron microscopies. There were lesser changes within the PVC samples with sulfadiazine tin complexes compared to the blank PVC sample. The dimethyltin(IV) complex was found to be the most efficient additive in stabilizing PVC against irradiation. The role played by the complexes in reducing the photodegradation of PVC was investigated, and a mechanism was proposed. J. VINYL ADDIT. TECHNOL., 26:370–379, 2020. © 2019 Society of Plastics Engineers
The wide‐ranging phenotypes of ergosterol biosynthesis mutants, and implications for microbial cell factories
Authors: Johnston Emily J. , Moses Tessa , Rosser Susan J.
Published: December 2019

Yeast strains have been used extensively as robust microbial cell factories for the production of bulk and fine chemicals, including biofuels (bioethanol), complex pharmaceuticals (antimalarial drug artemisinin and opioid pain killers), flavours, and fragrances (vanillin, nootkatone, and resveratrol). In many cases, it is of benefit to suppress or modify ergosterol biosynthesis during strain engineering, for example, to increase thermotolerance or to increase metabolic flux through an alternate pathway. However, the impact of modifying ergosterol biosynthesis on engineered strains is discussed sparsely in literature, and little attention has been paid to the implications of these modifications on the general health and well‐being of yeast. Importantly, yeast with modified sterol content exhibit a wide range of phenotypes, including altered organization and dynamics of plasma membrane, altered susceptibility to chemical treatment, increased tolerance to high temperatures, and reduced tolerance to other stresses such as high ethanol, salt, and solute concentrations. Here, we review the wide‐ranging phenotypes of viable Saccharomyces cerevisiae strains with altered sterol content and discuss the implications of these for yeast as microbial cell factories.
Smart Contracts in Insurance: A Law and Futurology Perspective
Authors: Borselli Angelo
Published: December 2019

Smart contracts are innovative contracts that differ from traditional ones in that they are self-executing, as they entail the possibility of representing contract terms in programming code that gets automatically executed on a blockchain or other distributed ledgers. Following the latest developments in blockchain technology, smart contracts have been the focus of growing attention and are currently among the major innovations that are taking place in financial services. This paper investigates the scope for their application in insurance both in the near and longer term, exploring the legal challenges that they pose. The analysis shows that in the near term smart contracts will be mainly exploited to automate underwriting, claims handling and payouts. It considers how the automation of these processes will operate at law and emphasises the impact that smart contracts can have especially on the reduction of transaction costs and on the very essence of the insurance contract—the insurer’s promise to pay. Building on current technological developments, the paper then turns to role that smart contracts can play in insurance in the longer term, advancing the prospect of the automation of the entire insurance contract. In particular, it argues that the interaction between smart contracts and artificial intelligence and machine learning can challenge traditional frameworks of thought such as incomplete contracting and, in the farther-distant future, will culminate in contracts that will both self-interpret and self-enforce their terms—what can be called the true smart contracts. The analysis identifies and addresses the main legal issues that can arise in this context, exploring how to strike a balance between the goal of fostering innovation and the need to ensure policyholder and investor protection.
Probeless non-invasive near-infrared spectroscopic bioprocess monitoring using microspectrometer technology
Authors: Zimmerleiter Robert , Kager Julian , Nikzad-Langerodi Ramin , Berezhinskiy Vladimir , Westad Frank , Herwig Christoph , Brandstetter Markus
Published: December 2019

Real-time measurements and adjustments of critical process parameters are essential for the precise control of fermentation processes and thus for increasing both quality and yield of the desired product. However, the measurement of some crucial process parameters such as biomass, product, and product precursor concentrations usually requires time-consuming offline laboratory analysis. In this work, we demonstrate the in-line monitoring of biomass, penicillin (PEN), and phenoxyacetic acid (POX) in a Penicilliumchrysogenum fed-batch fermentation process using low-cost microspectrometer technology operating in the near-infrared (NIR). In particular, NIR reflection spectra were taken directly through the glass wall of the bioreactor, which eliminates the need for an expensive NIR immersion probe. Furthermore, the risk of contaminations in the reactor is significantly reduced, as no direct contact with the investigated medium is required. NIR spectra were acquired using two sensor modules covering the spectral ranges 1350–1650 nm and 1550–1950 nm. Based on offline reference analytics, partial least squares (PLS) regression models were established for biomass, PEN, and POX either using data from both sensors separately or jointly. The established PLS models were tested on an independent validation fed-batch experiment. Root mean squared errors of prediction (RMSEP) were 1.61 g/L, 1.66 g/L, and 0.67 g/L for biomass, PEN, and POX, respectively, which can be considered an acceptable accuracy comparable with previously published results using standard process spectrometers with immersion probes. Altogether, the presented results underpin the potential of low-cost microspectrometer technology in real-time bioprocess monitoring applications.
The Bacterial Flora Associated with the Polyphagous Aphid Aphis gossypii Glover (Hemiptera: Aphididae) Is Strongly Affected by Host Plants
Authors: Xu Shifen , Jiang Liyun , Qiao Gexia , Chen Jing
Published: December 2019

Aphids live in symbiosis with a variety of bacteria, including the obligate symbiont Buchnera aphidicola and diverse facultative symbionts. The symbiotic associations for one aphid species, especially for polyphagous species, often differ across populations. In the present study, by using high-throughput 16S rRNA sequencing, we surveyed in detail the microbiota in natural populations of the cotton aphid Aphis gossypii in China and assessed differences in bacterial diversity with respect to host plant and geography. The microbial community of A. gossypii was dominated by a few heritable symbionts. Arsenophonus was the most dominant secondary symbiont, and Spiroplasma was detected for the first time. Statistical tests and ordination analyses showed that host plants rather than geography seemed to have shaped the associated symbiont composition. Special symbiont communities inhabited the Cucurbitaceae-feeding populations, which supported the ecological specialization of A. gossypii on cucurbits from the viewpoint of symbiotic bacteria. Correlation analysis suggested antagonistic interactions between Buchnera and coexisting secondary symbionts and more complicated interactions between different secondary symbionts. Our findings lend further support to an important role of the host plant in structuring symbiont communities of polyphagous aphids and will improve our understanding of the interactions among phytophagous insects, symbionts, and environments.
Cervical Spine Clearance in Trauma Patients with an Unreliable Physical Examination
Authors: Baekgaard Josefine S. , Christensen Rasmus Ejlersgaard , Lee Jae Moo , Eid Ahmed I. , Eskesen Trine G. , Steinmetz Jacob , Rasmussen Lars S. , King David R. , Velmahos George C.
Published: December 2019

Background

The objective of this study was to describe and compare the timing of cervical spine clearance in trauma patients with an unreliable physical examination.

Methods

We prospectively included adult trauma patients admitted with a cervical collar and an unreliable clinical examination (as defined by the NEXUS criteria) at two level 1 trauma centers: one in the USA (US) and one in Denmark (DK). We excluded patients with cervical spine injuries requiring a collar or surgery as treatment and patients with a collar placed after hospital arrival. The primary outcome was time from emergency department (ED) arrival to collar removal. Secondary outcomes included time to CT of the cervical spine (CTCS). At the US trauma center, an institutional protocol allowing cervical spine clearance exclusively by CTCS was in place. At the Danish trauma center, cervical spine clearance was based on a clinical evaluation by an orthopedic surgeon, usually after CTCS.

Results

A total of 113 patients were included (US: n = 56; DK: n = 57). The median age was 47 years, and 68% were males. The main reasons for an unreliable physical examination were a Glasgow Coma Scale score below 14 (35%), distracting injuries (26%), cervical spine tenderness (13%) and intoxication (13%). The injury severity score at the US trauma center was higher than at the DK trauma center (median: 17 vs. 11, p = 0.03). Both time to CTCS (median: 41 vs. 18 min, p < 0.0001) and time to collar removal (median: 1042 vs. 49 min, p < 0.0001) were significantly greater at the US trauma center.

Conclusions

Time to collar removal was significantly greater in a trauma center utilizing a cervical spine clearance protocol based on CTCS. As patients may develop complications related to the collar, future studies should clarify how early removal can be implemented without increasing the risk of morbidity.
IGHV mutational status of nodal marginal zone lymphoma by NGS reveals distinct pathogenic pathways with different prognostic implications
Authors: Granai Massimo , Amato Teresa , Di Napoli Arianna , Santi Raffaella , Vergoni Federica , Di Stefano Gioia , Mancini Virginia , Kovalchuk Sofya , Cencini Emanuele , Carta Alberto Giulio , Aversa Sara , Ziepert Marita , Cevenini Gabriele , Lazzi Stefano , Leoncini Lorenzo , Bellan Cristiana
Published: December 2019

The precise B cell of origin and molecular pathogenesis of nodal marginal zone lymphoma (NMZL) remain poorly defined. To date, due to the rarity of NMZL, the vast majority of already-published studies have been conducted on a limited number of samples and the technical approach to analyze the immunoglobulin genes was of amplifying rearranged variable region genes with the classical direct sequencing of the PCR products followed by cloning. Here, we studied the B cell Ig heavy-chain repertoires by next-generation sequencing (NGS) in 30 NMZL cases. Most of the cases were mutated (20/28; 71.5%) with homologies to the respective germ line genes ranging from 85 to 97, 83%, whereas 8/28 (28.5%) were unmutated. In addition, our results show that NMZL cases have a biased usage of specific immunoglobulin heavy-chain variable (IGHV) region genes. Moreover, we documented intraclonal diversity in all (100%) of the mutated cases and ongoing somatic hypermutations (SHM) have been confirmed by hundreds of reads. We analyzed the mutational pattern to detect and quantify antigen selection pressure and we found a positive selection in 4 cases, whereas in the remaining cases there was an unspecific stimulation. Finally, the disease-specific survival and the progression-free survival were significantly different between cases with mutated and unmutated IGHV genes, pointing out mutational status as a possible new biomarker in NMZL.
Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients
Authors: Ladfors Susanne Westphal , Lindahl Jenny K. , Hansson Sverker , Brandström Per , Andersson Rune , Jertborn Marianne , Lindh Magnus , Woxenius Susanne , Friman Vanda
Published: December 2019

Background

Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation.

Methods

A retrospective study of 58 children aged 1–17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log10 Geq/ml in > 50% of the samples during ≥ 6 months.

Results

At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5–6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7–13).

Conclusions

CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.
Vitamin D assessment in perioperative medicine and critical care
Authors: Zajic Paul , Heschl Stefan , Schörghuber Michael , Srekl-Filzmaier Petra , Stojakovic Tatjana , Weixler Viktoria , Zelzer Sieglinde , Amrein Karin
Published: December 2019

Background

There is controversy about the impact of acute illness on vitamin D levels. This study was carried out to assess the influence of perioperative fluid loading on 25-hydroxy-vitamin D [25(OH)D] levels. The study evaluated the clinical utility of a commonly available chemiluminescence assay (ECLIA, IDS-iSYS) and liquid chromatography/mass spectrometry (LC-MS/MS) in the diagnosis of vitamin D deficiency in this setting.

Methods

In this prospective observational pilot study in adult patients undergoing cardiovascular surgery on cardiopulmonary bypass (CPB), blood samples drawn at preoperative baseline (t1), after weaning from CPB (t2), on intensive care unit (ICU) admission (t3) and on the first (t4) and second (t5) postoperative days were analyzed.

Results

A total of 26 patients (130 samples) were included in this study. Fluid loading by CPB led to a median reduction of 25(OH)D by −22.6% (range −54.5% to −19.5%) between t1 and t2. Cohen’s kappa (κ) for method agreement for vitamin D deficiency (tested cut-off values 20 ng/ml and 12 ng/ml), was κ = 0.291 (p < 0.001) and κ = 0.469 (p < 0.001), respectively. The mean difference between measurements by ECLIA and LC-MS/MS was 4.8 ng/ml (±5.7), Pearson’s r for correlation was 0.73 (p < 0.001). The biologically inactive C3-epimer did not contribute to 25(OH)D levels assessed by LC-MS/MS.

Conclusion

The 25(OH)D measurements by chemiluminescence assays can noticeably deviate from those measured by LC-MS/MS, which can be considered the unequivocal gold standard. These assays may still be acceptably reliable in the screening for vitamin D deficiency, especially in the setting of low vitamin D levels. Stricter definitions, e.g. serum 25(OH)D levels lower than 12 ng/ml, may be used to diagnose deficiency with low false positive rate.

Trial Registration

DRKS00009216, German Clinical Trials Registry (www.drks.de)
The Premonitory Urge for Tics Scale in a large sample of children and adolescents: psychometric properties in a developmental context. An EMTICS study
Authors:   and the EMTICS collaborative group, Openneer Thaïra J. C. , Tárnok Zsanett , Bognar Emese , Benaroya-Milshtein Noa , Garcia-Delgar Blanca , Morer Astrid , Steinberg Tamar , Hoekstra Pieter J. , Dietrich Andrea
Published: December 2019

Premonitory urges are uncomfortable physical sensations preceding tics that occur in most individuals with a chronic tic disorder. The Premonitory Urge for Tics Scale (PUTS) is the most frequently used self-report measure to assess the severity of premonitory urges. We aimed to evaluate the psychometric properties of the PUTS in the largest sample size to date (n = 656), in children aged 3–16 years, from the baseline measurement of the longitudinal European Multicenter Tics in Children Study (EMTICS). Our psychometric evaluation was done in three age-groups: children aged 3–7 years (n = 103), children between 8 and 10 years (n = 253), and children aged 11–16 years (n = 300). The PUTS exhibited good internal reliability in children and adolescents, also under the age of 10, which is younger than previously thought. We observed significant but small correlations between the severity of urges and severity of tics and obsessive–compulsive symptoms, and between severity of urges and ratings of attention-deficit/hyperactivity disorder and internalizing and externalizing behaviors, however, only in children of 8–10 years. Consistent with previous results, the 10th item of the PUTS correlated less with the rest of the scale compared to the other items and, therefore, should not be used as part of the questionnaire. We found a two-factor structure of the PUTS in children of 11 years and older, distinguishing between sensory phenomena related to tics, and mental phenomena as often found in obsessive–compulsive disorder. The age-related differences observed in this study may indicate the need for the development of an age-specific questionnaire to assess premonitory urges.
Screening tools for early neuropsychological impairment after aneurysmal subarachnoid hemorrhage
Authors: Rautalin Ilari M. , Sebök Martina , Germans Menno R. , Korja Miikka , Dannecker Noemi , Zindel-Geisseler Olivia , Brugger Peter , Regli Luca , Stienen Martin N.
Published: December 2019

Background

Although most aneurysmal subarachnoid hemorrhage (aSAH) patients suffer from neuropsychological disabilities, outcome estimation is commonly based only on functional disability scales such as the modified Rankin Scale (mRS). Moreover, early neuropsychological screening tools are not used routinely.

Objective

To study whether two simple neuropsychological screening tools identify neuropsychological deficits (NPDs), among aSAH patients categorized with favorable outcome (mRS 0—2) at discharge.

Methods

We reviewed 170 consecutive aSAH patients that were registered in a prospective institutional database. We included all patients graded by the mRS at discharge, and who had additionally been evaluated by a neuropsychologist and/or occupational therapist using the Montreal Cognitive Assessment (MoCA) and/or Rapid Evaluation of Cognitive Function (ERFC). The proportion of patients with scores indicative of NPDs in each test were reported, and spearman correlation tests calculated the coefficients between the both neuropsychological test results and the mRS.

Results

Of the 42 patients (24.7%) that were evaluated by at least one neuropsychological test, 34 (81.0%) were rated mRS 0—2 at discharge. Among these 34 patients, NPDs were identified in 14 (53.9%) according to the MoCA and 8 (66.7%) according to the ERFC. The mRS score was not correlated with the performance in the MoCA or ERFC.

Conclusion

The two screening tools implemented here frequently identified NPDs among aSAH patients that were categorized with favorable outcome according to the mRS. Our results suggest that MoCA or ERFC could be used to screen early NPDs in favorable outcome patients, who in turn might benefit from early neuropsychological rehabilitation.
The impact of wall thickness and curvature on wall stress in patient-specific electromechanical models of the left atrium
Authors: Augustin Christoph M. , Fastl Thomas E. , Neic Aurel , Bellini Chiara , Whitaker John , Rajani Ronak , O’Neill Mark D. , Bishop Martin J. , Plank Gernot , Niederer Steven A.
Published: December 2019

The left atrium (LA) has a complex anatomy with heterogeneous wall thickness and curvature. The anatomy plays an important role in determining local wall stress; however, the relative contribution of wall thickness and curvature in determining wall stress in the LA is unknown. We have developed electromechanical finite element (FE) models of the LA using patient-specific anatomical FE meshes with rule-based myofiber directions. The models of the LA were passively inflated to 10mmHg followed by simulation of the contraction phase of the atrial cardiac cycle. The FE models predicted maximum LA volumes of 156.5 mL, 99.3 mL and 83.4 mL and ejection fractions of 36.9%, 32.0% and 25.2%. The median wall thickness in the 3 cases was calculated as $$1.32\, \pm \,0.78$$1.32±0.78 mm, $$1.21\, \pm \,0.85$$1.21±0.85 mm, and $$0.74\,\pm \,0.34$$0.74±0.34 mm. The median curvature was determined as $$0.159\,\pm \,0.080$$0.159±0.080 $$\hbox {mm}^{-1}$$mm-1, $$0.165\,\pm \,0.079\,\hbox {mm}^{-1}$$0.165±0.079mm-1, and $$0.166\,\pm \,0.077\,\hbox {mm}^{-1}$$0.166±0.077mm-1. Following passive inflation, the correlation of wall stress with the inverse of wall thickness and curvature was 0.55–0.62 and 0.20–0.25, respectively. At peak contraction, the correlation of wall stress with the inverse of wall thickness and curvature was 0.38–0.44 and 0.16–0.34, respectively. In the LA, the 1st principal Cauchy stress is more dependent on wall thickness than curvature during passive inflation and both correlations decrease during active contraction. This emphasizes the importance of including the heterogeneous wall thickness in electromechanical FE simulations of the LA. Overall, simulation results and sensitivity analyses show that in complex atrial anatomy it is unlikely that a simple anatomical-based law can be used to estimate local wall stress, demonstrating the importance of FE analyses.
Aberrant mitochondrial function in ageing and cancer
Authors: Whitehall Julia C. , Greaves Laura C.
Published: December 2019

Alterations in mitochondrial metabolism have been described as one of the major hallmarks of both ageing cells and cancer. Age is the biggest risk factor for the development of a significant number of cancer types and this therefore raises the question of whether there is a link between age-related mitochondrial dysfunction and the advantageous changes in mitochondrial metabolism prevalent in cancer cells. A common underlying feature of both ageing and cancer cells is the presence of somatic mutations of the mitochondrial genome (mtDNA) which we postulate may drive compensatory alterations in mitochondrial metabolism that are advantageous for tumour growth. In this review, we discuss basic mitochondrial functions, mechanisms of mtDNA mutagenesis and their metabolic consequences, and review the evidence for and against a role for mtDNA mutations in cancer development.
Seasonal and diel patterns in activity and habitat use by brook trout (Salvelinus fontinalis) in a small Newfoundland lake
Authors: Cote D. , Tibble B. , Curry R. A. , Peake S. , Adams B. K. , Clarke K. D. , Perry R.
Published: December 2019

Despite the challenges winter poses to salmonids inhabiting temperate and northern environments, there are relatively few studies that evaluate the factors that influence activity and habitat use during this season, particularly for lake environments that are ice-covered. This study examines brook trout depth distribution and movement (activity and range) in relation to temperature, light, and time of day across a 17-month period in a small lake in Newfoundland, Canada. Brook trout maintained elevated diurnal activity patterns throughout the year, despite seasonal changes in temperature, shifts in depth use, and prolonged, ice-induced darkness. Despite the tendency for relatively lower activity at night, brook trout remained active nocturnally, inferring a shift in foraging modes rather than a cessation of feeding. Winter movement velocities and ranges were less than other seasons but they occupied littoral areas that overlapped extensively with spring and fall core ranges. In contrast, summer core ranges of brook trout were principally comprised of areas with cooler water in the deep portion of the lake. As water temperature increased, daytime movement velocities increased in a log-linear fashion, whereas modeled nighttime movement velocity relationships with temperature were curvilinear and included the lowest movement velocities at 2–3 °C and the highest at the extremes of the occupied temperature range. The ability of brook trout to maintain diurnal activity patterns throughout a wide spectrum of environmental conditions suggests a strong behavioral and physiological capacity to adapt to their seasonally variable environment.
Cultivation of early life history stages of Porphyra dioica from the British Isles
Authors: Knoop J. , Griffin J. N. , Barrento S.
Published: December 2019

Bladed Bangiales of the genus Porphyra/Pyropia are highly valuable red algae and extensively farmed in South East Asia. Interest is rising in cultivating species local to the North East Atlantic but the control of the heteromorphic life cycle of native species remains difficult as previous studies reported high inter- and intraspecific variability in required cultivation conditions. Here, working with Porphyra dioica from a UK source population, we conducted a series of experiments investigating the influence of substrate, temperature, photoperiod and light intensity on the development of early life history stages (conchocelis (filamentous sporophyte) and young thalli (gametophyte)). Special focus was the influence of temperature and photoperiod on mature conchocelis to induce a conchospore mass release—the current bottleneck of European Porphyra cultivation. Sporophytes grew largest on an oyster shell substrate and under long day conditions at 18 °C. A decrease in temperature from 18 to 9 °C initiated a mass conchospore release (498 ± 146 spores mL−1) from a P. dioica conchocelis culture grown in suspension. Released conchospores germinated into small thalli on nylon ropes, with best growth (7.2 ± 0.9% day−1) at low temperatures of 9 °C. Conchospore germination increased with decreasing light intensity but germination success was generally very low (< 5%), indicating the cultivation protocol needs further improvement. Our results reflect the adaptation of P. diocia to seasonal environmental conditions in temperate regions and the importance of these conditions for the successful cultivation. We are the first to describe a mass conchospore release for P. diocia growing in suspension which has important implications for commercial production.
Riding the Wave of Credit: Are Longer Expansions Really a Bad Omen?
Authors: Castro Vítor , Martins Rodrigo
Published: December 2019

Some studies argue that credit booms that end up in banking crises are usually longer than those that end without creating havoc. However, they do not test this hypothesis empirically. This paper employs a duration model to assess the relationship between the length of credit booms and their outcome. The empirical analysis shows that credit expansions that end in banking crisis are indeed more prone to last longer than those that end softly. Furthermore, differences in length patterns are found to start in the build-up phase, extending to the unwinding phase of credit cycles.
Climate Variability Impact on the Spatiotemporal Characteristics of Drought and Aridityin Arid and Semi-Arid Regions
Authors: Mohammed Ruqayah , Scholz Miklas
Published: December 2019

Investigating the spatiotemporal distribution of climate data and their impact on the allocation of the regional aridity and meteorological drought, particularly in semi-arid and arid climate, it is critical to evaluate the climate variability effect and propose sufficient adaptation strategies. The coefficient of variation, precipitation concentration index and anomaly index were used to evaluate the climate variability, while the Mann-Kendall and Sen’s slope were applied for trend analysis, together with homogeneity tests. The aridity was evaluated using the alpha form of the reconnaissance drought index (Mohammed & Scholz, Water Resour Manag 31(1):531–538, 2017c), whereas drought episodes were predicted by applying three of the commonly used meteorological drought indices, which are the standardised reconnaissance drought index, standardized precipitation index and standardized precipitation evapotranspiration index. The Upper Zab River Basin (UZRB), which is located in the northern part of Iraq and covers a high range of climate variability, has been considered as an illustrative basin for arid and semi-arid climatic conditions. There were general increasing trends in average temperature and potential evapotranspiration and decreasing trends in precipitation from the upstream to the downstream of the UZRB. The long-term analysis of climate data indicates that the number of dry years has temporally risen and the basin has experienced succeeding years of drought, particularly after 1994/1995. There was a potential link between drought, aridity and climate variability. Pettitt’s, SNHT, Buishand’s and von Neumann’s homogeneity test results demonstrated that there is an evident alteration in the mean of the drought and aridity between the pre- and post-alteration point (1994).
Interventional Efforts to Reduce Psychological Distress after Orthopedic Trauma: A Systematic Review
Authors: Kirven James C. , Everhart Joshua S. , DiBartola Alex C. , Jones Jeremy , Flanigan David C. , Harrison Ryan
Published: December 2019

Background

Unanticipated severe injury to part of the musculoskeletal system, referred to as orthopedic trauma, can be debilitating. It can also be accompanied by equally debilitating psychological distress, but little is known about the effective interventions for psychological sequelae of orthopedic trauma.

Questions/Purposes

We sought to determine the effectiveness of interventions on psychological outcomes, such as post-traumatic stress disorder (PTSD), depression, and pain catastrophizing (feelings of helplessness, excessive rumination, and exaggerated description of pain), after major orthopedic trauma.

Methods

Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement as guidelines, we systematically searched Scopus, PubMed, and Google Scholar. Studies included for review were English-language interventional studies in an orthopedic trauma population that included assessment of post-injury psychological distress or disability as either a primary or secondary aim.

Results

Twelve studies were identified, including six randomized trials, three prospective cohort studies, and three retrospective cohort studies. Study sample sizes ranged from 48 to 569 patients, the mean age ranged from 29 to 52.8 years, and the percentage of male patients ranged from 38 to 90%. We examined four categories of interventions. Peer group treatment (one study) significantly reduced rates of depression but had low participation rates. Brief interventions to teach coping and self-efficacy skills (two studies) decreased depression, pain catastrophizing, and anxiety scores while increasing self-efficacy on short-term follow-up. Individualized counseling and rehabilitation (four studies) resulted in a consistent reduction in the risk of PTSD. Early amputation was found to result in lower rates of PSTD than limb salvage in US military personnel (four studies). One study examined surgeons’ confidence in dealing with possible psychological distress; surgeons who participated in a program on collaborative care were significantly more confident that they could help their patients with such issues.

Conclusion

Interventional strategies, including group interventions, brief individual interventions, longitudinal counseling, and consideration of early amputation in selected populations have proved effective in reducing negative psychological sequelae of major orthopedic trauma. Further research that determines the effects of interventions in this population is needed.
Web Application for Quantification of Traumatic Brain Injury-Induced Cortical Lesions in Adult Mice
Authors: Ciszek Robert , Andrade Pedro , Tapiala Jesse , Pitkänen Asla , Ndode-Ekane Xavier Ekolle
Published: December 2019

Disabilities resulting from traumatic brain injury (TBI) strongly correlate with the cytoarchitectonic part of the brain damaged, lesion area, and type of lesion. We developed a Web application to estimate the location of the lesion on mouse cerebral cortex caused by TBI induced by lateral fluid-percussion injury. The application unfolds user-determined TBI lesion measurements, e.g., from histologic sections to a reference template, and estimates the total lesion area, including the percentage of cortex damaged in different cytoarchitectural cortical regions. The resulting lesion can be visualized on a two-dimensional map of mouse cerebral cortex. The application also visualizes the development of the lesion over time when measurements from multiple time points are available. The web application was validated by comparing its performance to the manual method. The total area of the cortical lesion was similar between the manual (9.19 ± 0.66 mm2, range 4.25–14.93 mm2) and the automated analysis (9.27 ± 0.66 mm2, range 4.50–15.10 mm2) (p = 0.938). The results of the manual and automated analyses were strongly correlated (r = 0.999, p < 0.0001, Pearson correlation). The lesion localized in the same cytoarchitectonic regions when the unfolded map from the automated method was superimposed onto the map obtained using the manual method. The Web application-automated method is faster than the manual method in generating unfolded cortical lesion maps. The accuracy of the presented automated method in determining the anteroposterior level and outlining the lesion is equal to or greater than that of the manual method. Our application provides a novel tool for accurately quantifying and visualizing TBI lesions on mouse cerebral cortex.
Racial and Ethnic Differences in BRCA1/2 and Multigene Panel Testing Among Young Breast Cancer Patients
Authors: Jones T , Trivedi MS , Jiang X , Silverman T , Underhill M , Chung WK , Kukafka R , Crew KD
Published: December 2019

Genetic testing for hereditary breast and ovarian cancer (HBOC) is recommended for breast cancer patients diagnosed at age ≤ 50 years. Our objective was to examine racial/ethnic differences in genetic testing frequency and results among diverse breast cancer patients. A retrospective cohort study among women diagnosed with breast cancer at age ≤ 50 years from January 2007 to December 2017 at Columbia University in New York, NY. Among 1503 diverse young breast cancer patients, nearly half (46.2%) completed HBOC genetic testing. Genetic testing completion was associated with younger age, family history of breast cancer, and earlier stage, but not race/ethnicity or health insurance status. Blacks had the highest frequency of pathogenic/likely pathogenic (P/LP) variants (18.6%), and Hispanics and Asians had the most variants of uncertain significance (VUS), 19.0% and 21.9%, respectively. The percentage of women undergoing genetic testing increased over time from 15.3% in 2007 to a peak of 72.8% in 2015. Over the same time period, there was a significant increase in P/LP and VUS results. Due to uncertainty about the clinical implications of P/LP variants in moderate penetrance genes and VUSs, our findings underscore the need for targeted genetic counseling education, particularly among young minority breast cancer patients.
Groundwater quality assessment of Shahdadkot, Qubo Saeed Khan and Sijawal Junejo Talukas of District Qambar Shahdadkot, Sindh
Authors: Lanjwani Muhammad Farooque , Khuhawar Muhammad Yar , Khuhawar Taj Muhammad Jahangir
Published: December 2019

The study examines the water quality of Shahdadkot, Qubo Saeed Khan and Sijawal Junejo talukas of Qambar Shahdadkot District, less affected by industrial contamination. A total of 38 groundwater samples were collected and analysed for 28 parameters. The results indicated that 57.89% samples were not suitable for drinking purpose with total dissolved solids above than maximum permissible limit of World Health Organization (WHO) (1000 mg/L). The pH, total phosphate, orthophosphate and nitrite were within WHO limits. The concentration of essential metals more than half samples, fluoride in 60.52% and heavy metals 0–50% were contaminated higher than permissible limits of WHO. The statistical analysis of water quality parameters was also carried out to evaluate coefficient of determination among the parameters, cluster analysis and principal component analysis. Water quality determined for irrigation based on Kelly index (KI), sodium percentage (Na%), chloride–sulphate ratio, sodium adsorption ratio, permeability index (PI), chloroalkaline indices 1 (CAI-1), residual sodium carbonate and chloride bicarbonate ratio indicated that samples (55 to 100%) could be used for irrigation purposes. The consumption of water with high concentration of salts and fluoride above the permissible limits may be a cause of a number of diseases in the area.