bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 1, randomized, double‐blind, placebo‐controlled study to evaluate the safety, tolerability, and pharmacokinetics of single and multiple doses of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adult subjects
Authors: Ermer James , Martin Patrick , Corcoran Mary , Matsuo Yumiko
Published: November 2019

Aim

To assess safety, tolerability, and pharmacokinetics of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adults.

Methods

A phase 1, double‐blind, randomized, placebo‐controlled, single‐ and multiple‐dose study in Japanese and Caucasian subjects. Subjects received lisdexamfetamine 20 mg or placebo on Day 1, then lisdexamfetamine 20 mg/d (Days 4‐8), 50 mg/d (Days 9‐13), 70 mg/d (Days 14‐18), or matching placebo. Pharmacokinetic parameters for lisdexamfetamine and d‐amphetamine were estimated by noncompartmental analysis.

Results

Fifteen Japanese and 19 Caucasian subjects were enrolled and randomized. The lisdexamfetamine and d‐amphetamine plasma concentration‐time curves were similar for both ethnic groups following single and multiple doses. Mean area under the concentration‐time curves for d‐amphetamine were higher (by 11%‐15%) in Japanese than Caucasian subjects following multiple dosing of lisdexamfetamine. Mean bodyweight was 17% lower in Japanese than Caucasian subjects. Weight‐corrected means for oral clearance were similar in both ethnic groups, with no unexpected accumulation of d‐amphetamine. Lisdexamfetamine was generally well tolerated by both ethnic groups, with no serious adverse events reported. The 10/12 Japanese and 11/16 Caucasian subjects who received lisdexamfetamine completed the study; two Japanese and three Caucasian subjects discontinued due to adverse events. Most adverse events were of mild severity.

Conclusion

Pharmacokinetics were generally similar for Japanese and Caucasian subjects; the minor differences observed were likely due to bodyweight differences in the two ethnic groups. Lisdexamfetamine was generally well tolerated. Adverse events were consistent with the established safety profile of lisdexamfetamine and were similar in both ethnic groups.
Effects of the ACTIVity And TEchnology (ACTIVATE) intervention on health‐related quality of life and fatigue outcomes in breast cancer survivors
Authors: Vallance Jeff K. , Nguyen Nga H. , Moore Melissa M. , Reeves Marina M. , Rosenberg Dori E. , Boyle Terry , Milton Shakira , Friedenreich Christine M. , English Dallas R. , Lynch Brigid M.
Published: November 2019

Background

The ACTIVATE Trial examined the efficacy of a wearable‐based intervention to increase physical activity and reduce sedentary behavior in breast cancer survivors. This paper examines the effects of the intervention on health‐related quality of life (HRQoL) and fatigue at 12 weeks (T2; end of intervention) and 24 weeks (T3; follow‐up).

Methods

Inactive and postmenopausal women who had completed primary treatment for stage I‐III breast cancer were randomized to intervention or waitlist control. Physical activity and sedentary behavior were measured by Actigraph and activPAL accelerometers at baseline (T1), end of the intervention (T2), and 12 weeks follow‐up (T3). HRQoL and fatigue were measured using the Functional Assessment of Cancer Therapy‐Breast (FACT‐B) and the Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐Fatigue). Primary intervention effects were evaluated comparing intervention and waitlist group at T2 using repeated measures mixed effects models.

Results

Overall, 83 women were randomized and trial retention was high (94%). A 4.6‐point difference in fatigue score was observed between groups at T2 (95% CI: 1.3, 7.8) indicating improvement in fatigue profiles in the intervention group. In within groups analyses, the intervention group reported a 5.1‐point increase in fatigue from baseline to T2 (95% CI: 2.0, 8.2) and a 3.3‐point increase from baseline to T3 (95% CI: 0.1, 6.41).

Conclusions

Despite small improvements in fatigue profiles, no effects on HRQoL were observed. While the ACTIVATE Trial was associated with improvements in physical activity and sedentary behavior, more intensive or longer duration interventions may be needed to facilitate changes in HRQoL.
Ultrasound and magnetic resonance imaging for group stratification and treatment monitoring in the transgenic adenocarcinoma of the mouse prostate model
Authors: Fagerland Stein‐Martin T. , Hill Deborah K. , van Wamel Annemieke , de Lange Davies Catharina , Kim Jana
Published: November 2019

Background

The transgenic adenocarcinoma of the mouse prostate (TRAMP) is a widely used genetically engineered spontaneous prostate cancer model. However, both the degree of malignancy and time of cancer onset vary. While most mice display slowly progressing cancer, a subgroup develops fast‐growing poorly differentiated (PD) tumors, making the model challenging to use. We investigated the feasibility of using ultrasound (US) imaging to screen for PD tumors and compared the performances of US and magnetic resonance imaging (MRI) in providing reliable measurements of disease burden.

Methods

TRAMP mice (n = 74) were screened for PD tumors with US imaging and findings verified with MRI, or in two cases with gross pathology. PD tumor volume was estimated with US and MR imaging and the methods compared (n = 11). For non‐PD mice, prostate volume was used as a marker for disease burden and estimated with US imaging, MRI, and histology (n = 11). The agreement between the measurements obtained by the various methods and the intraobserver variability (IOV) was assessed using Bland‐Altman analysis.

Results

US screening showed 81% sensitivity, 91% specificity, 72% positive predictive value, and 91% negative predictive value. The smallest tumor detected by US screening was 14 mm3 and had a maximum diameter of 2.6 mm. MRI had the lowest IOV for both PD tumor and prostate volume estimation. US IOV was almost as low as MRI for PD tumor volumes but was considerably higher for prostate volumes.

Conclusions

US imaging was found to be a good screening method for detecting PD tumors and estimating tumor volume in the TRAMP model. MRI had better repeatability than US, especially when estimating prostate volumes.
Quantum Dot Optomechanics in Suspended Nanophononic Strings
Authors: Vogele Anja , Sonner Maximilian M. , Mayer Benjamin , Yuan Xueyong , Weiß Matthias , Nysten Emeline D. S. , Covre da Silva Saimon F. , Rastelli Armando , Krenner Hubert J.
Published: November 2019

The optomechanical coupling of quantum dots and flexural mechanical modes is studied in suspended nanophononic strings. The investigated devices are designed and monolithically fabricated on an (Al)GaAs heterostructure. Radio frequency elastic waves with frequencies ranging between and 400 MHz are generated as Rayleigh surface acoustic waves on the unpatterned substrate and injected as Lamb waves in the nanophononic string. Quantum dots inside the nanophononic string exhibit a 15‐fold enhanced optomechanical modulation compared to those dynamically strained by the Rayleigh surface acoustic wave. Detailed finite element simulations of the phononic mode spectrum of the nanophononic string confirm that the observed modulation arises from valence band deformation potential coupling via shear strain. The corresponding optomechanical coupling parameter is quantified to . This value exceeds that reported for vibrating nanorods by approximately one order of magnitude at 100 times higher frequencies. Using this value, a derived vertical displacement in the range of 10 nm is deduced from the experimentally observed modulation. The results represent an important step toward the creation of large scale optomechanical circuits interfacing single optically active quantum dots with optical and mechanical waves.
Injectable and Radiopaque Liquid Metal/Calcium Alginate Hydrogels for Endovascular Embolization and Tumor Embolotherapy
Authors: Fan Linlin , Duan Minghui , Xie Zhongchen , Pan Keqin , Wang Xuelin , Sun Xuyang , Wang Qian , Rao Wei , Liu Jing
Published: November 2019

Improved endovascular embolization can contribute to assistant treatment for patients. However, many traditional embolic materials, such as metal microcoils or liquid embolic agents, are associated with limitations of coil migration or recanalization. Herein, as the first trial, an injectable and radiopaque liquid metal/calcium alginate (LM/CA) hydrogel is introduced and fabricated as a candidate for endovascular embolization and tumor embolotherapy through developing LM droplets as radiopaque units into biocompatible calcium alginate cross‐linked network. The adoption of LM droplets makes hydrogels radiopaque under X‐ray and CT scan, which significantly facilitates the tracking of material location during surgical vascular operation. In addition, in vitro and in vivo experiments prove that such smart hydrogel could convert from liquid to solid rapidly via cross‐linking, showing pretty flexible and controllable functions. Benefiting from these properties, the hydrogel can be performed in blood vessels through injection via syringes and then served as an embolic material for endovascular embolization procedures. In vivo experiments demonstrate that such hydrogels can occlude arteries and block blood flow until they ultimately lead to ischemic necrosis of tumors and partial healthy tissues. Overall, the present LM/CA hydrogels are promising to be developed as new generation embolic materials for future tumor embolotherapy.
Universal Nanocarrier Ink Platform for Biomaterials Additive Manufacturing
Authors: Guzzi Elia A. , Bovone Giovanni , Tibbitt Mark W.
Published: November 2019

Ink engineering is a fundamental area of research within additive manufacturing (AM) that designs next‐generation biomaterials tailored for additive processes. During the design of new inks, specific requirements must be considered, such as flowability, postfabrication stability, biointegration, and controlled release of therapeutic molecules. To date, many (bio)inks have been developed; however, few are sufficiently versatile to address a broad range of applications. In this work, a universal nanocarrier ink platform is presented that provides tailored rheology for extrusion‐based AM and facilitates the formulation of biofunctional inks. The universal nanocarrier ink (UNI) leverages reversible polymer–nanoparticle interactions to form a transient physical network with shear‐thinning and self‐healing properties engineered for direct ink writing (DIW). The unique advantage of the material is that a range of functional secondary polymers can be combined with the UNI to enable stabilization of printed constructs via secondary cross‐linking as well as customized biofunctionality for tissue engineering and drug delivery applications. Specific UNI formulations are used for bioprinting of living tissue constructs and DIW of controlled release devices. The robust and versatile nature of the UNI platform enables rapid formulation of a broad range of functional inks for AM of advanced biomaterials.
Design and validation of a C++ code generator from Abstract State Machines specifications
Authors: Bonfanti Silvia , Gargantini Angelo , Mashkoor Atif
Published: November 2019

According to best practices of model‐driven engineering, the implementation of a system should be obtained from its model through a systematic model‐to‐code transformation. We present in this paper a methodology supported by the Asm2C++ tool, which allows the users to generate C++ code from abstract state machine models. Thanks to Asm2C++, the implementation is generated in a seamless manner with an assurance of potential bug freeness of the generated code. Following the same approach, model‐based testing suggests deriving also (unit) tests from abstract models. We extend the Asm2C++ tool such that it can automatically produce unit tests for the generated code. Abstract test sequences, either generated randomly or through model checking, are translated to concrete C++ unit tests using the Boost library. In a similar manner, also, scenarios are generated in a behavior‐driven development (BDD) approach. To guarantee the correctness of the transformation process, we define a mechanism to test the correctness of the model‐to‐code transformation with respect to two main criteria: syntactical correctness and semantic correctness, which is based on the definition of conformance between the specification and the code. Using this approach, we have devised a process able to test the generated code by reusing unit tests. The process has been used to validate our model‐to‐code transformations.
Computational methods for ribosome profiling data analysis
Authors: Kiniry Stephen J. , Michel Audrey M. , Baranov Pavel V.
Published: November 2019

Since the introduction of the ribosome profiling technique in 2009 its popularity has greatly increased. It is widely used for the comprehensive assessment of gene expression and for studying the mechanisms of regulation at the translational level. As the number of ribosome profiling datasets being produced continues to grow, so too does the need for reliable software that can provide answers to the biological questions it can address. This review describes the computational methods and tools that have been developed to analyze ribosome profiling data at the different stages of the process. It starts with initial routine processing of raw data and follows with more specific tasks such as the identification of translated open reading frames, differential gene expression analysis, or evaluation of local or global codon decoding rates. The review pinpoints challenges associated with each step and explains the ways in which they are currently addressed. In addition it provides a comprehensive, albeit incomplete, list of publicly available software applicable to each step, which may be a beneficial starting point to those unexposed to ribosome profiling analysis. The outline of current challenges in ribosome profiling data analysis may inspire computational biologists to search for novel, potentially superior, solutions that will improve and expand the bioinformatician's toolbox for ribosome profiling data analysis.

This article is characterized under:

Translation > Ribosome Structure/Function

RNA Evolution and Genomics > Computational Analyses of RNA

Translation > Translation Mechanisms

Translation > Translation Regulation
Protocols for Northern Analysis of Exosome Substrates and Other Noncoding RNAs
Authors: Cruz Cristina , Houseley Jonathan
Published: November 2019

Over the past decade a plethora of noncoding RNAs (ncRNAs) have been identified, initiating an explosion in RNA research. Although RNA sequencing methods provide unsurpassed insights into ncRNA distribution and expression, detailed information on structure and processing are harder to extract from sequence data. In contrast, northern blotting methods provide uniquely detailed insights into complex RNA populations but are rarely employed outside specialist RNA research groups. Such techniques are generally considered difficult for nonspecialists, which is unfortunate as substantial technical advances in the past few decades have solved the major challenges. Here we present simple, reproducible and highly robust protocols for separating glyoxylated RNA on agarose gels and heat denatured RNA on polyacrylamide–urea gels using standard laboratory electrophoresis equipment. We also provide reliable transfer and hybridization protocols that do not require optimization for most applications. Together, these should allow any molecular biology lab to elucidate the structure and processing of ncRNAs of interest.
The Bridge: Redux—The Breakdown of Normative Conviviality
Authors: Ristilammi Per-Markku
Published: November 2019

In this chapter the concept of conviviality is used as an analytic concept around which recent developments concerning the changing role of state borders in Europe are discussed. It aims at highlighting a specific kind of normative state-driven conviviality through the example of the transnational Öresund Bridge, between Sweden and Denmark, thus showing how the concept can be used in an analysis of the changing roles, or even states of the state. The Bridge and the surrounding region was part of a bi-national project of conviviality at its inauguration in 2000, but 15 years later the border controls that were put in place in response to the so called refugee-crisis, which signaled a breakdown of this specific form of conviviality. The chapter shows how this breakdown of state conviviality opens up for a new form of biopolitical regime at the border.
Charting a Convivial Continuum in British Post-war Popular Music 1948–2018
Authors: Boothby Hugo
Published: November 2019

This chapter seeks to chart a convivial continuum within Caribbean influenced British post-war popular music. Conviviality is understood here to find expression in social formations where essentialised racial identifications and their associated hierarchies breakdown. Popular music is an important site at which to trace convivial formation and its relationship with migration within the UK because it offers a productive site at which vibrant intermixture and combination have taken place. In this chapter, these processes of intermixture and combination are understood in terms of creolisation. Calypso, reggae, post-punk, jungle, two-step garage, dubstep and grime are explored as sites of signifying-practice and corporeal affect with potential to articulate identity positions and experiences that are anti-essential and capable of disrupting racial hierarchies.
Creolisation as a Recipe for Conviviality
Authors: Eriksen Thomas Hylland
Published: November 2019

This chapter argues that the historical and contemporary experiences of the Creole world have created a set of possible social and cultural configurations which encompass cosmopolitanism, create conditions for conviviality and expand the project of living together by engaging the arts and music, language and food, as well as transgressing social boundaries. The miracle of creolisation can be described as an enormous output of cultural creativity growing out of a history of suffering, displacement and oppression. However, the social effects of creolisation are perhaps more important, leading to the emergence of social identities which are unbounded, exogamous as well as endogamous, internally diverse and striking a balance between group and individual which is simultaneously flexible and robust, an inoculation against divisive identity politics.
Creolising Conviviality: Thinking Relational Ontology and Decolonial Ethics Through Ivan Illich and Édouard Glissant
Authors: Gutiérrez Rodríguez Encarnación
Published: November 2019

Following Ivan Illich and Édouard Glissant, this chapter aims to discuss the conceptual and visionary implications of creolising conviviality. It does so by first providing an account of Illich’s concept of “conviviality” in terms of its material and ethical underpinning. Second, it looks at contemporary empirical research on conviviality in order to understand the complexities that this perspective sets out to study. Third, the chapter establishes that conviviality needs to be placed in relation to Glissant’s creolisation, a visionary outlook of an antagonistic living together. Creolisation as a rhizomatic relational conceptualisation of society departs from the critical understanding of contemporary societies as entrenched in historically produced racialised hierarchies, resulting in economic and social inequalities which impede living together based on equal economic distribution and social justice. The chapter concludes with some thoughts on a decolonial ethics of creolising conviviality.
Sozialer Status, soziale Beziehungen und Gesundheit
Authors: Vonneilich Nico
Published: November 2019

Das vorliegende Kapitel gibt einen Überblick über die Forschung zu den Zusammenhängen zwischen sozialem Status, sozialen Beziehungen und Gesundheit. Zwei Fragen stehen hierbei im Vordergrund: Können soziale Beziehungen zu einer Erklärung der Zusammenhänge zwischen sozialem Status und Gesundheit beitragen (sog. Hypothese der differenziellen Exposition)? Variiert der Zusammenhang zwischen sozialen Beziehungen und Gesundheit je nach untersuchter sozialer Statusgruppe (sog. Hypothese der differenziellen Vulnerabilität)? Zu beiden Theorien werden die jeweiligen begrifflichen und theoretischen Grundlagen beschrieben und der Stand der Forschung zusammengefasst. Es zeigt sich, dass insbesondere Hinweise zum Erklärungsbeitrag sozialer Beziehungen zu gesundheitlichen Ungleichheiten vorliegen, während die Ergebnisse in Bezug der Hypothese der differenziellen Vulnerabilität insgesamt eher uneindeutig sind.
Netzwerkanalyse – eine methodische Annäherung
Authors: Gamper Markus
Published: November 2019

Netzwerke bestehen aus Akteuren, die durch Beziehungen miteinander verbunden sind und dessen Verbindungen sich zu unterschiedlichen sozialen Strukturen zusammensetzen.

Man geht davon aus, dass soziale Netzwerke auf die Akteure wirken und Akteure wiederum die Netzwerke beeinflussen.

Es findet sich eine Unterscheidung zwischen Gesamtnetzwerken und egozentrierten Netzwerken. Bei der Gesamtnetzwerkanalyse werden die jeweiligen Akteure und deren Relationen innerhalb vordefinierter Grenzen betrachtet. Bei egozentrierten Netzwerken steht die interpersonale Vernetzung eines bestimmten Akteurs im Zentrum der Analyse.
Multi-scale modeling of drug binding kinetics to predict drug efficacy
Authors: Clarelli Fabrizio , Liang Jingyi , Martinecz Antal , Heiland Ines , Abel zur Wiesch Pia
Published: November 2019

Optimizing drug therapies for any disease requires a solid understanding of pharmacokinetics (the drug concentration at a given time point in different body compartments) and pharmacodynamics (the effect a drug has at a given concentration). Mathematical models are frequently used to infer drug concentrations over time based on infrequent sampling and/or in inaccessible body compartments. Models are also used to translate drug action from in vitro to in vivo conditions or from animal models to human patients. Recently, mathematical models that incorporate drug-target binding and subsequent downstream responses have been shown to advance our understanding and increase predictive power of drug efficacy predictions. We here discuss current approaches of modeling drug binding kinetics that aim at improving model-based drug development in the future. This in turn might aid in reducing the large number of failed clinical trials.
Development and optimization of a hybridization technique to type the classical class I and class II B genes of the chicken MHC
Authors: Potts Nicola D. , Bichet Coraline , Merat Laurence , Guitton Edouard , Krupa Andrew P. , Burke Terry A. , Kennedy Lorna J. , Sorci Gabriele , Kaufman Jim
Published: November 2019

The classical class I and class II molecules of the major histocompatibility complex (MHC) play crucial roles in immune responses to infectious pathogens and vaccines as well as being important for autoimmunity, allergy, cancer and reproduction. These classical MHC genes are the most polymorphic known, with roughly 10,000 alleles in humans. In chickens, the MHC (also known as the BF-BL region) determines decisive resistance and susceptibility to infectious pathogens, but relatively few MHC alleles and haplotypes have been described in any detail. We describe a typing protocol for classical chicken class I (BF) and class II B (BLB) genes based on a hybridization method called reference strand-mediated conformational analysis (RSCA). We optimize the various steps, validate the analysis using well-characterized chicken MHC haplotypes, apply the system to type some experimental lines and discover a new chicken class I allele. This work establishes a basis for typing the MHC genes of chickens worldwide and provides an opportunity to correlate with microsatellite and with single nucleotide polymorphism (SNP) typing for approaches involving imputation.
Simulator training and residents’ first laparoscopic hysterectomy: a randomized controlled trial
Authors: Jokinen Ewa , Mikkola Tomi S. , Härkki Päivi
Published: November 2019

Background

Hysterectomy rates are decreasing in many countries, and virtual reality simulators bring new opportunities into residents’ surgical education. The objective of this study was to evaluate the effect of training in laparoscopic hysterectomy module with virtual reality simulator on surgical outcomes among residents performing their first laparoscopic hysterectomy.

Methods

This randomized study was carried out at the Department of Obstetrics and Gynecology in Helsinki University Hospital and Hyvinkää Hospital. We recruited twenty residents and randomly signed half of them to train ten times with the laparoscopic hysterectomy module on a virtual reality simulator, while the rest represented the control group. Their first laparoscopic hysterectomy was video recorded and assessed later by using the Objective Structured Assessment of Technical Skills (OSATS) forms and Visual Analog Scale (VAS). The scores and surgical outcomes were compared between the groups.

Results

The mean OSATS score for the Global Rating Scale (GRS) was 17.0 (SD 3.1) in the intervention group and 11.2 (SD 2.4) in the control group (p = 0.002). The mean procedure-specific OSATS score was 20.0 (SD 3.3) and 16.0 (SD 2.8) (p = 0.012), and the mean VAS score was 55.0 (SD 14.8) and 29.9 (SD 14.9) (p = 0.001). Operative time was 144 min in the intervention group and 165 min in the control group, but the difference did not reach statistical significance (p = 0.205). There were no differences between the groups in blood loss or direct complications.

Conclusion

Residents training with a virtual reality simulator prior to the first laparoscopic hysterectomy seem to perform better in the actual live operation. Thus, a virtual reality simulator hysterectomy module could be considered as a part of laparoscopic training curriculum.
Postoperative rendezvous endoscopic retrograde cholangiopancreaticography as an option in the management of choledocholithiasis
Authors: Syrén Eva-Lena , Sandblom Gabriel , Eriksson Staffan , Eklund Arne , Isaksson Bengt , Enochsson Lars
Published: November 2019

Background

Rendezvous endoscopic retrograde cholangiopancreaticography (ERCP) is a well-established method for treatment of choledocholithiasis. The primary aim of this study was to determine how different techniques for management of common bile duct stone (CBDS) clearance in patients undergoing cholecystectomy have changed over time at tertiary referral hospitals (TRH) and county/community hospitals (CH). The secondary aim was to see if postoperative rendezvous ERCP is a safe, effective and feasible alternative to intraoperative rendezvous ERCP in the management of CBDS.

Methods

Data were retrieved from the Swedish registry for cholecystectomy and ERCP (GallRiks) 2006–2016. All cholecystectomies, where CBDS were found at intraoperative cholangiography, and with complete 30-day follow-up (n = 10,386) were identified. Data concerning intraoperative and postoperative complications, readmission and reoperation within 30 days were retrieved for patients where intraoperative ERCP (n = 2290) and preparation for postoperative ERCP were performed (n = 2283).

Results

Intraoperative ERCP increased (7.5% 2006; 43.1% 2016) whereas preparation for postoperative ERCP decreased (21.2% 2006; 17.2% 2016) during 2006–2016. CBDS management differed between TRHs and CHs. Complications were higher in the postoperative rendezvous ERCP group: Odds Ratio [OR] 1.69 (95% confidence interval [CI] 1.16–2.45) for intraoperative complications and OR 1.50 (CI 1.29–1.75) for postoperative complications. Intraoperative bleeding OR 2.46 (CI 1.17–5.16), postoperative bile leakage OR 1.89 (CI 1.23–2.90) and postoperative infection with abscess OR 1.55 (CI 1.05–2.29) were higher in the postoperative group. Neither post-ERCP pancreatitis, postoperative bleeding, cholangitis, percutaneous drainage, antibiotic treatment, ICU stay, readmission/reoperation within 30 days nor 30-day mortality differed between groups.

Conclusions

Techniques for management of CBDS found at cholecystectomy have changed over time and differ between TRH and CH. Rendezvous ERCP is a safe and effective method. Even though intraoperative rendezvous ERCP is the preferred method, postoperative rendezvous ERCP constitutes an acceptable alternative where ERCP resources are lacking or limited.
Phenotypic segregation of seedling UCB-1 hybrid pistachio rootstock
Authors: Jacygrad Ewelina , Preece John E. , Palmer William J. , Michelmore Richard , Golino Deborah
Published: November 2019

Key message

The growth of UCB-1 pistachio rootstock seedlings in the earliest years is a poor predictor of subsequent growth. Therefore, rogueing during the 1st years of growth is not effective.

The UCB-1 hybrid, produced from a controlled cross betweenPistacia atlantica(female) andP. integerrima(male), is the main pistachio rootstock used in the USA. Variation has been observed in orchards planted with seedling UCB-1 rootstocks for over 20 years. Reduced vigor and stunting of some trees are of particular concern to growers due to decreased nut yield. This study was conducted to better understand the growth of non-grafted UCB-1, as well as between UCB-1 rootstock andPistacia verascions in commercial orchards. Phenotypic traits were evaluated in the non-grafted orchard. Grafted tree data were collected for bothP. verafemale scions and their UCB-1 seedling rootstocks in commercial orchards. The uniformity of tree height, trunk caliper, and canopy volume decreased annually during the first 5 years of growth. Individual tree growth was not linear and was poorly synchronized among siblings, causing the population to become increasingly less uniform as it aged. Consequently, growth in the earliest years is a poor predictor of subsequent growth. The strongest correlation was between growth parameters during the later years. There was a significant correlation between rootstock and scion caliper of the grafted trees in commercial orchards, with the least vigorous rootstocks producing the least vigorous scions. These data confirm the need to reliably rogue out seedlings that later will not be vigorous; however, our data show that rogueing based on the 1st years of growth is ineffective. This study suggests the need to develop predictive molecular markers for rootstock vigor.
External quality assessment for molecular diagnostic laboratories in Belgium: Can we improve it?
Authors: Dufraing Kelly , Lierman Els , Vankeerberghen Anne , Franke Sabine , Dequeker Els
Published: November 2019

External quality assessment (EQA) is an essential part of performance monitoring for molecular laboratories. At the moment, a national law regulates participation in EQA schemes for clinical biology and pathology in Belgium. This study aimed (1) to get insights on how laboratories organize their EQA participation, (2) to poll satisfaction with the current situation (selection of EQA programs in advance by a governmental body), (3) to provide guidance for choosing the most relevant EQA provider and (4) to propose a new model for national performance monitoring. A survey was sent to Belgian laboratories performing molecular tests in the field of microbiology, hematology and pathology with (1) general questions on how they select an EQA provider and (2) their satisfaction of each provider. In total, 25 molecular laboratories [microbiology (N = 13), hematology (N = 8) and pathology (N = 4)] from 14 different hospitals completed the survey regarding their EQA organization. All three laboratory groups indicated to prefer EQA schemes using real patient materials as well as those with varying targets and concentrations. For molecular microbiology and hematology, schemes with a syndromic approach are sought. Since annual participation in EQA becomes burdensome in most laboratories, this paper also offers a risk-based strategy for determining the participation frequency. Based on the needs of Belgian laboratories, three proposals were made: (1) for the proper selection of an EQA scheme, (2) for determining the minimal participation frequency and (3) for the national organization of EQA schemes.
The Mediating Role of Depression in the Relationship Between Body Image Dissatisfaction and Cyberbullying Perpetration
Authors: Balta Sabah , Emirtekin Emrah , Kircaburun Kagan , Griffiths Mark D.
Published: November 2019

Preliminary evidence suggests that psychopathological factors (e.g., depression) are associated with higher engagement in cyberbullying perpetration, and those with elevated body image dissatisfaction (BID) are more susceptible to depression. However, the possible impact of body image dissatisfaction (BID) on cyberbullying remains untested. The present study examined the direct and indirect relationships of BID with cyberbullying via depression among a sample of 507 university students (mean age, 21.37 years; range 18–44 years). t tests showed that males had a higher prevalence of cyberbullying than females. Structural equation modeling indicated that BID was directly and indirectly associated with cyberbullying via depression among the total sample and males. However, BID was only indirectly related to cyberbullying via depression among females. Depression fully explained the relationship between BID and cyberbullying among females, although there were additional mediating factors between BID and cyberbullying among males. The findings are in accordance with theoretical models suggesting that individuals’ personal characteristics including psychopathological factors are associated with cyberbullying. Furthermore, males attempt to cope with their body image–related psychopathology with more externalizing behaviors than females.
Risk Stratification for Sudden Cardiac Death in Non-Ischaemic Dilated Cardiomyopathy
Authors: Akhtar M. , Elliott P. M.
Published: November 2019

Purpose of Review

Non-ischaemic dilated cardiomyopathy (DCM) occurs in 1 in 2500 individuals in the general population and is associated with considerable morbidity and mortality. Studies involving large numbers of unselected DCM patients have led to consensus guidelines recommending implantable cardioverter-defibrillator (ICD) implantation for protection against sudden cardiac death (SCD) in those with LVEF ≤35%. The purpose of this article is to review the literature for other potential markers including serological, electrocardiographic, echocardiographic, cardiac magnetic resonance, ambulatory ECG and genetic data, to highlight other potential markers that may optimise risk stratification for SCD in this cohort and thereby allow a more personalized approach to ICD-implantation.

Recent Findings

Recent studies including the Danish study to assess the efficacy of ICDs in patients with non-ischemic systolic heart failure on mortality (DANISH) trial have questioned the benefits of ICD implantation in this group of patients with no changes in all-cause mortality. Recent pooled cohorts of patients with genetic DCM and in particular in those with Lamin A/C (LMNA) mutations have identified patients at increased risk of SCD and allowed the creation of algorithms to prognosticate SCD risk in mutation carriers. Furthermore, genetic testing has identified other DCM-causing genes including filamin C (FLNC) and RBM20 which may be associated with higher rates of ventricular arrhythmia.

To date, risk-stratification for SCD has been hampered by the utilisation of heterogenous subsets of idiopathic DCM patients and by use of static risk models where predictions are based on a single time point with a lack of consideration of disease progression. The current focus of personalised risk-stratification for SCD is shifting towards better characterisation of underlying DCM aetiology and the development of multi-parametric risk-stratification models that incorporate time-dependent disease characteristics and novel biomarkers.
An elderly man with progressive focal nodular hyperplasia
Authors: Hamada Koichi , Saitoh Satoshi , Nishino Noriyuki , Fukushima Daizo , Techigawara Kae , Koyanagi Ryota , Horikawa Yoshinori , Shiwa Yoshiki , Sakuma Hideo , Kondo Fukuo
Published: November 2019

Patients with focal nodular hyperplasia (FNH) develop benign hepatocellular nodules. FNH most frequently occurs in young women. There are no reports of the onset of FNH in elderly men. We report a case of FNH in an elderly man, whose nodules increased in number and size. The patient underwent surgery for carcinoma of the left renal pelvis at 69 years of age; no liver masses were noted on yearly follow-up contrast-enhanced computed tomography (CECT). Ten years later, CECT revealed a hepatic mass, and magnetic resonance imaging suggested FNH. The nodules increased in number and size in subsequent follow-up examinations.
The 2019 H. Paul Douglass Lecture: I Can't Keep Quiet: Engaging with Scholarly Research on Religion
Authors: Bruce Tricia C.
Published: November 2019

Methodologies used by social scientists grant access to quiet worlds and otherwise hidden truths. Social scientists are akin to strangers, trusted with secrets. The 2019 H. Paul Douglass Lecture proposes that scholars who engage with research on religion ought to listen quietly, but not keep quiet. We can transform the quiet to which we are privy into the collective. I illustrate the imperative to speak research out loud using the case example of the National Abortion Attitudes Study. Personal knowledge becomes collective revelation and, sometimes, social change.
How Uncertain is the Survival Extrapolation? A Study of the Impact of Different Parametric Survival Models on Extrapolated Uncertainty About Hazard Functions, Lifetime Mean Survival and Cost Effectiveness
Authors: Kearns Ben , Stevens John , Ren Shijie , Brennan Alan
Published: November 2019

Background and Objective

The extrapolation of estimated hazard functions can be an important part of cost-effectiveness analyses. Given limited follow-up time in the sample data, it may be expected that the uncertainty in estimates of hazards increases the further into the future they are extrapolated. The objective of this study was to illustrate how the choice of parametric survival model impacts on estimates of uncertainty about extrapolated hazard functions and lifetime mean survival.

Methods

We examined seven commonly used parametric survival models and described analytical expressions and approximation methods (delta and multivariate normal) for estimating uncertainty. We illustrate the multivariate normal method using case studies based on four representative hypothetical datasets reflecting hazard functions commonly encountered in clinical practice (constant, increasing, decreasing, or unimodal), along with a hypothetical cost-effectiveness analysis.

Results

Depending on the survival model chosen, the uncertainty in extrapolated hazard functions could be constant, increasing or decreasing over time for the case studies. Estimates of uncertainty in mean survival showed a large variation (up to sevenfold) for each case study. The magnitude of uncertainty in estimates of cost effectiveness, as measured using the incremental cost per quality-adjusted life-year gained, varied threefold across plausible models. Differences in estimates of uncertainty were observed even when models provided near-identical point estimates.

Conclusions

Survival model choice can have a significant impact on estimates of uncertainty of extrapolated hazard functions, mean survival and cost effectiveness, even when point estimates were similar. We provide good practice recommendations for analysts and decision makers, emphasizing the importance of considering the plausibility of estimates of uncertainty in the extrapolated period as a complementary part of the model selection process.
Wilderness Medical Society Clinical Practice Guidelines for Spinal Cord Protection
Authors: Hawkins Seth C. , Williams Jason , Bennett Brad L. , Islas Arthur , Kayser Dietrich Whitfield , Quinn Robert
Published: November 2019

The Wilderness Medical Society reconvened an expert panel to update best practice guidelines for spinal cord protection during trauma management. This panel, with membership updated in 2018, was charged with the development of evidence-based guidelines for management of the injured or potentially injured spine in wilderness environments. Recommendations are made regarding several parameters related to spinal cord protection. These recommendations are graded based on the quality of supporting evidence and balance the benefits and risks/burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians. Key recommendations include the concept that interventions should be goal oriented (spinal cord/column protection in the context of overall patient and provider safety) rather than technique oriented (immobilization). This evidence-based, goal-oriented approach does not support the immobilization of suspected spinal injuries via rigid collars or backboards.
An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
Authors: Thoma Brent , Goerzen Scott , Horeczko Timothy , Roland Damian , Tagg Andrew , Chan Teresa M , Bruijns Stevan , Riddell Jeff ,   The METRIQ Podcast Study Collaborators
Published: November 2019

Objectives

Podcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.

Methods

An international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.

Results

390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.

Conclusions

An international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
Feasibility of connecting regional research programs to national multisite trials emanating from the CTSA Trial Innovation Network
Authors: Hassell Laurie , Gregor Charlie , Melvin Ann , Goss Christopher , Coker Robert H. , Laukes Cindi , Albritton Sandra , Brant Jeannine , Amoroso Paul , Whitener Nichole , Tuttle Katherine R.
Published: November 2019

A collaborative research model was developed and tested to enable regional healthcare systems to join multisite clinical trials emanating from the Clinical and Translational Science Award (CTSA) Trial Innovation Network (TIN) by the Institute of Translational Health Sciences at the University of Washington and the Northwest Participant and Clinical Interactions (NW PCI) Network. The NW PCI is a collaborative group of regional research programs located at medical centers, healthcare systems, and universities across Washington, Wyoming, Alaska, Montana, and Idaho. This article describes the purpose, development, barriers, and initial experience with feasibility assessment for TIN-supported studies in the NW PCI. The tools and processes of the NW PCI Network were adapted to enable network sites to assess studies for clinical relevance and feasibility. Seven of seventeen TIN-supported studies were reviewed for consideration; three of which resulted in successful completion of study documentation for site selection by NW PCI sites. The NW PCI/TIN model can be adapted by other CTSAs to increase involvement of regional research programs in national multisite clinical research studies. Barriers to expanding TIN-supported trials to regional networks include short timelines for study document submissions, insufficient site reimbursement rates, and non-feasible study designs.
The Twilight of the Two-State Solution in Israel-Palestine: Shared Sovereignty and Nonterritorial Autonomy as the New Dawn
Authors: Nimni Ephraim
Published: November 2019

This article analyzes the international consensus on the Israeli-Palestinian conflict that there should be a two state solution and finds it unworkable on several counts. The conflict has no territorial solution: high population density makes partition impossible without leaving unwanted pockets of one people in the territory of the other; it is not possible for any Israeli government to dismantle settlements in the West Bank without causing a civil war; and in such a small and overcrowded territory, it is not feasible to have monocultural nation-states when the population is now evenly divided between the two conflicting national communities that reside in overlapping areas. Demographic forecasts show in the short term, a decrease in the proportion of Israeli Jews and an increase in the proportion of Palestinians. In the face of this stalemate, the article recalls the 90-year-old proposal by enlightened Jewish personalities to create a binational state under the modality of national-cultural autonomy. Furthermore, and paradoxically, in a reversal of the situation 90 years ago, Palestinian Israeli citizens are slowly creating a bottom-up series of autonomous communal organizations that provide self-government without territorial control, a model for nonterritorial autonomy in a manner that reminds of the earlier proposals of the Jewish personalities. The article concludes that this could potentially be a way out of this stalled and protracted conflict. A plurinational state in Israel-Palestine based on the model of National Cultural Autonomy with shared sovereignty and collective rights for all communities.