bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of health-system pharmacy administration and leadership residencies
Authors: Santalo Oscar , Farano Joelle , Igwe Jacqualine , Deyhim Niaz
Published: February 2020

Purpose

To perform an inquiry with response measurement from health-system pharmacy administration and leadership (HSPAL) residency program directors and residents to distinguish variances between the programs and identify enhancement opportunities for key stakeholders.

Methods

Members from the Pharmacy Administration Resident Collaboration Research Committee developed separate 20-question survey instruments to assess the strengths and areas of opportunity for HSPAL residency programs from the perspective of residency program directors and residents. The survey instruments were designed to evaluate the level of pharmacy service integration across HSPAL programs nationwide.

Results

Nearly half of the residency program directors within the listserv (40.74%, 33/81) participated in the survey. The recognized areas of opportunity by residency program directors include community pharmacy leadership, professional organization involvement, sterile compounding, and supply chain management. About a third (32.54%, 41/126) of the residents participated in the survey. Residents reported the least exposure to community pharmacy leadership, human resource management, informatics, professional organizations, and ambulatory care/specialty rotations. The overall recommendations for HSPAL residency programs are to incorporate C-suite–level experiences, improve alumni engagement, develop longitudinal human resource/financial experiences, and encourage resident credential obtainment.

Conclusion

In order to foster professional and leadership growth for HSPAL residents, residency programs should consider incorporating C-suite–level experiences, longitudinal human resource/finance experiences, alumni engagement opportunities, rotation variety, professional organization involvement, and support in credential obtainment.
Small spaces, big impacts: contributions of micro-environmental variation to population persistence under climate change
Authors: Denney Derek A , Jameel M Inam , Bemmels Jordan B , Rochford Mia E , Anderson Jill T
Published: February 2020

Individuals within natural populations can experience very different abiotic and biotic conditions across small spatial scales owing to microtopography and other micro-environmental gradients. Ecological and evolutionary studies often ignore the effects of micro-environment on plant population and community dynamics. Here, we explore the extent to which fine-grained variation in abiotic and biotic conditions contributes to within-population variation in trait expression and genetic diversity in natural plant populations. Furthermore, we consider whether benign microhabitats could buffer local populations of some plant species from abiotic stresses imposed by rapid anthropogenic climate change. If microrefugia sustain local populations and communities in the short term, other eco-evolutionary processes, such as gene flow and adaptation, could enhance population stability in the longer term. We caution, however, that local populations may still decline in size as they contract into rare microhabitats and microrefugia. We encourage future research that explicitly examines the role of the micro-environment in maintaining genetic variation within local populations, favouring the evolution of phenotypic plasticity at local scales and enhancing population persistence under global change.
The Disrespectfulness of Weighted Survival Lotteries
Authors: Adams Joseph
Published: February 2020

If we can save the lives of only one of multiple groups of people, we might be inclined simply to save whichever group is largest. We may worry, though, that automatically saving the largest group fails to take each saveable individual sufficiently into account, offering some of these individuals no chance at all of being rescued. Still wanting to give larger groups higher chances of survival, we may then say that we ought to employ a proportionally weighted lottery to determine which group to save. In this paper, I argue that this would be a mistake. Given the most plausible way of specifying it, the weighted-lottery view itself fails to treat each saveable individual with equal moral respect.
Predator defense is shaped by risk, brood value and social group benefits in a cooperative breeder
Authors: Teunissen Niki , Kingma Sjouke A , Peters Anne
Published: February 2020

Predation is a major cause of mortality and nest failure in birds. Cooperative predator defense can enhance nest success and adult survival but, because it is inherently risky, dynamic risk assessment theory predicts that individuals modify defense behavior according to the risk posed by the predator. Parental investment theory, on the other hand, predicts that reproductive payoffs (brood value) determine investment in nest defense. We propose that, in cooperative breeders, fitness benefits deriving from the survival of other group members may additionally influence defense behavior (social group benefits theory). We tested predictions of these theories in the cooperatively breeding purple-crowned fairy-wren, Malurus coronatus, where brood value is higher for breeders, but social group benefits more important for helpers. We recorded experimentally induced individual defense behaviors in response to predator models presented near nests, representing differing levels of threat to nests and adults. As predicted, 1) individuals engaged in less risky defenses when encountering a more dangerous predator (dynamic risk assessment theory); 2) individuals defended older broods more often, and breeders defended more than helpers (parental investment theory); and 3) helpers were more likely to respond to a predator of adults (social group benefits theory). Our findings highlight that predator defense in cooperative breeders is complex, shaped by the combination of immediate risk and multiple benefits.
ZIAQ: a quantile regression method for differential expression analysis of single-cell RNA-seq data
Authors: Zhang Wenfei , Wei Ying , Zhang Donghui , Xu Ethan Y
Published: February 2020

Motivation

Single-cell RNA sequencing (scRNA-seq) has enabled the simultaneous transcriptomic profiling of individual cells under different biological conditions. scRNA-seq data have two unique challenges that can affect the sensitivity and specificity of single-cell differential expression analysis: a large proportion of expressed genes with zero or low read counts ('dropout' events) and multimodal data distributions.

Results

We have developed a zero-inflation-adjusted quantile (ZIAQ) algorithm, which is the first method to account for both dropout rates and complex scRNA-seq data distributions in the same model. ZIAQ demonstrates superior performance over several existing methods on simulated scRNA-seq datasets by finding more differentially expressed genes. When ZIAQ was applied to the comparison of neoplastic and non-neoplastic cells from a human glioblastoma dataset, the ranking of biologically relevant genes and pathways showed clear improvement over existing methods.

Availability and implementation

ZIAQ is implemented in the R language and available at https://github.com/gefeizhang/ZIAQ.

Supplementary information

Supplementary data are available at Bioinformatics online.
Anterior visual system imaging to investigate energy failure in multiple sclerosis
Authors: Kleerekooper Iris , Petzold Axel , Trip S Anand
Published: February 2020

Mitochondrial failure and hypoxia are key contributors to multiple sclerosis pathophysiology. Importantly, improving mitochondrial function holds promise as a new therapeutic strategy in multiple sclerosis. Currently, studying mitochondrial changes in multiple sclerosis is hampered by a paucity of non-invasive techniques to investigate mitochondrial function of the CNS in vivo. It is against this backdrop that the anterior visual system provides new avenues for monitoring of mitochondrial changes. The retina and optic nerve are among the metabolically most active structures in the human body and are almost always affected to some degree in multiple sclerosis. Here, we provide an update on emerging technologies that have the potential to indirectly monitor changes of metabolism and mitochondrial function. We report on the promising work with optical coherence tomography, showing structural changes in outer retinal mitochondrial signal bands, and with optical coherence angiography, quantifying retinal perfusion at the microcapillary level. We show that adaptive optics scanning laser ophthalmoscopy can visualize live perfusion through microcapillaries and structural changes at the level of single photoreceptors and neurons. Advantages and limitations of these techniques are summarized with regard to future research into the pathology of the disease and as trial outcome measures.
Structural and functional footprint of visual snow syndrome
Authors: Schankin Christoph J , Maniyar Farooq H , Chou Denise E , Eller Michael , Sprenger Till , Goadsby Peter J
Published: February 2020

Patients with visual snow syndrome suffer from a continuous pan-field visual disturbance, additional visual symptoms, tinnitus, and non-perceptional symptoms. The pathophysiology of visual symptoms might involve dysfunctional visual cortex. So far, the extra-visual system has not been investigated. We aimed at identifying structural and functional correlates for visual and non-visual symptoms in visual snow syndrome. Patients were compared to age- and sex-matched controls using 18F-2-fluoro-2-deoxy-d-glucose PET (n = 20 per group) and voxel-based morphometry (n = 17 per group). Guided by the PET results, region of interest analysis was done in voxel-based morphometry to identify structural-functional correspondence. Grey matter volume was assessed globally. Patients had corresponding hypermetabolism and cortical volume increase in the extrastriate visual cortex at the junction of the right lingual and fusiform gyrus. There was hypometabolism in the right superior temporal gyrus and the left inferior parietal lobule. Patients had grey matter volume increases in the temporal and limbic lobes and decrease in the superior temporal gyrus. The corresponding structural and functional alterations emphasize the relevance of the visual association cortex for visual snow syndrome. The broad structural and functional footprint, however, confirms the clinical impression that the disorder extends beyond the visual system.
A Large-Scale Genetic Correlation Scan Between Intelligence and Brain Imaging Phenotypes
Authors: Cheng Shiqiang , Wu Cuiyan , Qi Xin , Liu Li , Ma Mei , Zhang Lu , Cheng Bolun , Liang Chujun , Li Ping , Kafle Om Prakash , Wen Yan , Zhang Feng
Published: February 2020

Limited efforts have been paid to evaluate the potential relationships between structural and functional brain imaging and intelligence until now. We performed a two-stage analysis to systematically explore the relationships between 3144 brain image-derived phenotypes (IDPs) and intelligence. First, by integrating genome-wide association studies (GWAS) summaries data of brain IDPs and two GWAS summary datasets of intelligence, we systematically scanned the relationship between each of the 3144 brain IDPs and intelligence through linkage disequilibrium score regression (LDSC) analysis. Second, using the individual-level genotype and intelligence data of 160 124 subjects derived from UK Biobank datasets, polygenetic risk scoring (PRS) analysis was performed to replicate the common significant associations of the first stage. In the first stage, LDSC identified 6 and 2 significant brain IDPs significantly associated with intelligence dataset1 and dataset2, respectively. It is interesting that NET100_0624 showed genetic correlations with intelligence in the two datasets of intelligence. After adjusted for age and sex as the covariates, NET100_0624 (P = 5.26 × 10−20, Pearson correlation coefficients = −0.02) appeared to be associated with intelligence by PRS analysis of UK Biobank samples. Our findings may help to understand the genetic mechanisms of the effects of brain structure and function on the development of intelligence.
A Semiquantitative Screening Test and Quantitative Assay for Total Fecal Fat
Authors: Nelson William R , O’Hopp Susan J
Published: February 2020

The gravimetric analysis of total fecal fat by a proposed chloroform extraction procedure has been shown to compare very closely with an accepted procedure involving a petroleum ether extraction, at all levels of fecal fat. The decrease in the density of the chloroform by the fecal fat is used as a semiquantitative measure of fat concentration. This is accomplished by noting the bouyancy of the chloroform extract in sodium bromide solutions of the appropriate density. If the rapid screening test indicates a possible fecal fat level above the acceptable maximum, an aliquot of the same extract is then assayed gravimetrically.
The impact of patient sex on the response to intramyocardial mesenchymal stem cell administration in patients with non-ischaemic dilated cardiomyopathy
Authors: Florea Victoria , Rieger Angela C , Natsumeda Makoto , Tompkins Bryon A , Banerjee Monisha N , Schulman Ivonne H , Premer Courtney , Khan Aisha , Valasaki Krystalenia , Heidecker Bettina , Mantero Alejandro , Balkan Wayne , Mitrani Raul D , Hare Joshua M
Published: February 2020

Aims

Sex differences impact the occurrence, presentation, prognosis, and response to therapy in heart disease. Particularly, the phenotypic presentation of patients with non-ischaemic dilated cardiomyopathy (NIDCM) differs between men and women. However, whether the response to mesenchymal stem cell (MSC) therapy is influenced by sex remains unknown. We hypothesize that males and females with NIDCM respond similarly to MSC therapy.

Methods and results

Male (n = 24) and female (n = 10) patients from the POSEIDON-DCM trial who received MSCs via transendocardial injections were evaluated over 12 months. Endothelial function was measured at baseline and 3 months post-transendocardial stem cell injection (TESI). At baseline, ejection fraction (EF) was lower (P = 0.004) and end-diastolic volume (EDV; P = 0.0002) and end-systolic volume (ESV; P = 0.0002) were higher in males vs. females. In contrast, baseline demographic characteristics, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and 6-min walk test (6MWT) were similar between groups. EF improved in males by 6.2 units (P = 0.04) and in females by 8.6 units (P = 0.04; males vs. females, P = 0.57). EDV and ESV were unchanged over time. The MLHFQ score, New York Heart Association (NYHA) class, endothelial progenitor cell-colony forming units, and serum tumour necrosis factor alpha improved similarly in both groups.

Conclusion

Despite major differences in phenotypic presentation of NIDCM in males and females, this study is the first of its kind to demonstrate that MSC therapy improves a variety of parameters in NIDCM irrespective of patient sex. These findings have important clinical and pathophysiologic implications regarding the impact of sex on responses to cell-based therapy for NIDCM.
Quality of Care Standards in Inflammatory Bowel Diseases: a European Crohn’s and Colitis Organisation [ECCO] Position Paper
Authors: Fiorino Gionata , Lytras Theodore , Younge Lisa , Fidalgo Catarina , Coenen Sofie , Chaparro Maria , Allocca Mariangela , Arnott Ian , Bossuyt Peter , Burisch Johan , Campmans-Kuijpers Marjo , de Ridder Lissy , Dignass Axel , Drohan Ciara , Feakins Roger , Gilardi Daniela , Grosek Jan , Groß Evelyn , Hart Ailsa , Jäghult Susanna , Katsanos Konstantinos , Lönnfors Sanna , Panis Yves , Perovic Marko , Pierik Marieke , Rimola Jordi , Tulchinsky Hagit , Gisbert Javier P
Published: February 2020

The management of inflammatory bowel disease [IBD] is complex, and requires tight control of disease activity, close monitoring to avoid treatment side effects, health care professionals with expertise in IBD, and an interdisciplinary, holistic approach. Despite various efforts to standardise structures, processes, and outcomes,1–8 and due to the high variability at the local, national, and international levels, there are still no clear definitions or outcome measures available to establish quality of care standards for IBD patients which are applicable in all contexts and all countries. For this reason, the European Crohn’s and Colitis Organisation [ECCO] supported the construction of a list of criteria summarising current standards of care in IBD. The list comprises 111 quality standard points grouped into three main domains [structure n = 31, process n = 42, outcomes n = 38] and is based on scientific evidence, interdisciplinary expert consensus, and patient-oriented perspectives. The list of proposed criteria is intended to represent the position of ECCO regarding the optimum quality of care that should be available to patients. Since health care systems and regulations vary considerably between countries, this list may require adaptation at local and national levels. It is recognised that not all these criteria that have been identified as optimal will be available in every unit. However, ECCO will continue its efforts to develop and coordinate projects and initiatives that will help to guarantee optimal quality of care for all IBD patients.
Strategies to improve the accuracy of lung stapling in uniportal and multiportal thoracoscopic sublobar lung resections
Authors: Sato Masaaki
Published: February 2020

The challenges in video-assisted thoracic surgery for sublobar lung resection include difficulty in tumour localization by palpation and difficulty in determining appropriate resection lines. Virtual-assisted lung mapping (VAL-MAP), a bronchoscopic preoperative multispot lung dye-marking technique, allows for both tumour localization and determination of resection lines. To facilitate stapler-based resection, the AMAGAMI or ‘incomplete grasping’ stapler technique is useful to adjust the alignment of the stapler and resection lines. However, when the lung tissue to be stapled is thick, there is unavoidable uncertainty in the staple line inside the lung. We experimentally demonstrated that up to 1 cm of slippage of lung parenchyma occurs at stapling when the stapled lung tissue is >1 cm thick. VAL-MAP 2.0 is a new generation of VAL-MAP combining multispot dye markings with intrabronchial microcoil placement, allowing for 3-dimensional lung mapping and intraoperative navigation using fluoroscopy. The uncertainty of stapling in the lung parenchyma can be partly overcome by VAL-MAP 2.0.
A Multipoint Felled-Tree Validation of Height–Age Modeled Growth Rates
Authors: Hemingway Halli , Kimsey Mark
Published: February 2020

Accurate measures of forest site productivity are essential for forest-management planning. The most common measure of site productivity is breast height–age site index (BHASI)—the expected height at a reference age. Error from including early growth in productivity estimates and limited applicability of any one BHASI model warrant development of alternative methods. Exploring alternatives may only be necessary if regional BHASI models are not accurately predicting growth rates. We compared modeled height growth rates for Rocky Mountain Douglas-fir (Pseudotsuga menziesii var. glauca) to felled-tree measurements to evaluate relative performance of a regional BHASI model. An orthogonal sampling design ensured samples were collected across a range of site factors known to influence Douglas-fir growth rates. Growth rates for each 10 m section were calculated and compared to BHASI modeled growth rates. The regional BHASI model underpredicted growth rates from breast height to 30 m. Observed growth rates from 10 to 30 m accounted for the majority of underprediction relative to BHASI modeled growth rates. An alternative multipoint method of defining site productivity is described. More research comparing BHASI and alternative methods is needed, given the growth rate error associated with one-point site productivity assessment.
Implementation of initiatives to prevent student stress: process evaluation findings from the Healthy High School study
Authors: Bonnesen Camilla Thørring , Jensen Marie P , Madsen Katrine R , Toftager Mette , Rosing Johanne A , Krølner Rikke F
Published: February 2020

Process evaluation of public health interventions is important for understanding intervention results and can help explain why interventions succeed or fail. This study evaluated implementation of a school-based intervention combining educational and environmental strategies to prevent stress among Danish high school students. We investigated dose delivered, dose received, fidelity, appreciation, barriers and facilitators at the 15 intervention schools using mixed methods and multiple data sources: questionnaires among students, teachers and school coordinators; semi-structured interviews with school coordinators; telephone interviews with student counsellors; and focus group interviews with students and teachers. Implementation varied by schools and classes. Half of the intervention schools delivered the environmental strategies. For the educational strategies, dose delivered differed according to intervention provider. Students reported a lower dose received compared with dose delivered reported by school staff. Overall, student counsellors, school coordinators and students—especially those with low perceived stress—were satisfied with the stress preventive initiatives while teacher satisfaction varied. Five main barriers and three facilitators for implementation were identified. The use of multiple data sources and data methods created new knowledge of the implementation process which is important for the interpretation of effect evaluation and development of future interventions.
Prevalence and Risk Factors of Substance Use Disorder in Inflammatory Bowel Disease
Authors: Carney Heather , Marrie Ruth Ann , Bolton James M , Patten Scott B , Graff Lesley A , Bernstein Charles N , Kowalec Kaarina
Published: February 2020

Background

Substance use disorders (SUDs) impose a substantial individual and societal burden; however, the prevalence and associated factors in persons with inflammatory bowel disease (IBD) are largely unknown. We evaluated the prevalence and risk factors of SUD in an IBD cohort.

Methods

Inflammatory bowel disease participants (n = 247) were recruited via hospital- and community-based gastroenterology clinics, a population-based IBD research registry, and primary care providers as part of a larger cohort study of psychiatric comorbidity in immune-mediated inflammatory diseases. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders IV was administered to participants to identify lifetime SUD, anxiety disorder, and major depressive disorder. Additional questionnaires regarding participants’ sociodemographic and clinical characteristics were also completed. We examined demographic and clinical factors associated with lifetime SUD using unadjusted and adjusted logistic regression modeling.

Results

Forty-one (16.6%) IBD participants met the criteria for a lifetime diagnosis of an SUD. Factors associated with elevated odds of SUD were ever smoking (adjusted odds ratio [aOR], 2.96; 95% confidence interval [CI], 1.17–7.50), male sex (aOR, 2.44; 95% CI, 1.11–5.36), lifetime anxiety disorder (aOR, 2.41; 95% CI, 1.08–5.37), and higher pain impact (aOR, 1.08; 95% CI, 1.01–1.16).

Conclusions

One in six persons with IBD experienced an SUD, suggesting that clinicians should maintain high index of suspicion regarding possible SUD, and inquiries about substance use should be a part of care for IBD patients, particularly for men, smokers, and patients with anxiety disorders and pain.
Advanced three-dimensionally engineered simulation model for aortic valve and proximal aorta procedures
Authors: Russo Marco , Koenigshofer Markus , Stoiber Martin , Werner Paul , Gross Christoph , Kocher Alfred , Laufer Guenther , Moscato Francesco , Andreas Martin
Published: February 2020

OBJECTIVES

A 3-dimensionally (3D) engineered model for simulation of aortic valve and proximal aortic procedures is a reliable tool both for training young surgeons and for simulating complex cases. To achieve a realistic simulation, the artificial model should reproduce the angles and orientations of the cardiac structures based on the patient’s anatomical condition, reproduce tissue mechanical characteristics and be easy to obtain and easy to use. The goal of the study was the production and validation of realistic training models, based on the patient’s actual anatomical characteristics, to provide training for aortic valve procedures.

METHODS

An anatomical model was manufactured using 3D printing and silicone casting. The digital anatomical model was obtained by segmenting computed tomography imaging. The segmented geometrical images were processed and a casting mould was designed. The mould was manufactured on a 3D printer. Silicone was cast into the mould; after curing, the finished model was ready. The realistic reproduction was evaluated by mechanical hardness tests and a survey by cardiac surgeons.

RESULTS

Six 3D silicone models were produced that represented the patient’s anatomy including aortic valve leaflets, aortic root with coronary ostia, ascending aorta and proximal arch. Aortic valve replacement was performed, and 100% of the participants evaluated the model in a survey as perfectly reproducing anatomy and surgical handling.

CONCLUSIONS

We produced a realistic, cost-effective simulator for training purposes and for simulation of complex surgical cases. The model reproduced the real angulation and orientation of the aortic structures inside the mediastinum, permitting a real-life simulation of the desired procedure. This model offers opportunities to simulate various surgical procedures.
Less NMDA Receptor Binding in Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex Associated With Reported Early-Life Adversity but Not Suicide
Authors: Underwood Mark D , Bakalian Mihran J , Johnson Virginia L , Kassir Suham A , Ellis Steven P , Mann J John , Arango Victoria
Published: February 2020

Background

Glutamate is an excitatory neurotransmitter binding to 3 classes of receptors, including the N-methyl, D-aspartate (NMDA) receptor. NMDA receptor binding is lower in major depression disorder and suicide. NMDA receptor blocking with ketamine can have antidepressant and anti-suicide effects. Early-life adversity (ELA) may cause glutamate-mediated excitotoxicity and is more common with major depression disorder and in suicide decedents. We sought to determine whether NMDA-receptor binding is altered with suicide and ELA.

Methods

A total 52 postmortem cases were organized as 13 quadruplets of suicide and non-suicide decedents matched for age, sex, and postmortem interval, with or without reported ELA (≤16 years). Tissue blocks containing dorsal prefrontal (BA8), dorsolateral prefrontal (BA9), or anterior cingulate (BA24) cortex were collected at autopsy. Psychiatrically healthy controls and suicide decedents underwent psychological autopsy to determine psychiatric diagnoses and details of childhood adversity. NMDA receptor binding was determined by quantitative autoradiography of [3H]MK-801 binding (displaced by unlabeled MK-801) in 20-µm-thick sections.

Results

[3H]MK-801 binding was not associated with suicide in BA8, BA9, or BA24. However, [3H]MK-801 binding with ELA was less in BA8, BA9, and BA24 independent of suicide (P < .05). [3H]MK-801 binding was not associated with age or postmortem interval in any brain region or group.

Conclusions

Less NMDA receptor binding with ELA is consistent with the hypothesis that stress can cause excitotoxicity via excessive glutamate, causing either NMDA receptor downregulation or less receptor binding due to neuron loss consequent to the excitotoxicity.
A numerical-analysis-focused comparison of several finite volume schemes for a unipolar degenerate drift-diffusion model
Authors: Cancès Clément , Chainais-Hillairet Claire , Fuhrmann Jürgen , Gaudeul Benoît
Published: February 2020

In this paper we consider a unipolar degenerate drift-diffusion system where the relation between the concentration of the charged species $c$ and the chemical potential $h$ is $h(c)=\log \frac{c}{1-c}$. We design four different finite volume schemes based on four different formulations of the fluxes. We provide a stability analysis and existence results for the four schemes. The convergence proof with respect to the discretization parameters is established for two of them. Numerical experiments illustrate the behaviour of the different schemes.
Novel Variants of Respiratory Syncytial Virus A ON1 Associated With Increased Clinical Severity of Bronchiolitis
Authors: Midulla Fabio , Di Mattia Greta , Nenna Raffaella , Scagnolari Carolina , Viscido Agnese , Oliveto Giuseppe , Petrarca Laura , Frassanito Antonella , Arima Serena , Antonelli Guido , Pierangeli Alessandra
Published: February 2020

Background

A study of respiratory syncytial virus-A (RSV A) genotype ON1 genetic variability and clinical severity in infants hospitalized with bronchiolitis over 6 epidemic seasons (2012–2013 to 2017–2018) was carried out.

Methods

From prospectively enrolled term infants hospitalized for bronchiolitis, samples positive for RSV A ON1 (N = 139) were sequenced in the second half of the G gene. Patients’ clinical data were obtained from medical files and each infant was assigned a clinical severity score. ANOVA comparison and adjusted multinomial logistic regression were used to evaluate clinical severity score and clinical parameters.

Results

The phylogenetic analysis of 54 strains showed 3 distinct clades; sequences in the last 2 seasons differed from previous seasons. The most divergent and numerous cluster of 2017–2018 strains was characterized by a novel pattern of amino acid changes, some in antigenic sites. Several amino acid changes altered predicted glycosylation sites, with acquisition of around 10 new O-glycosylation sites. Clinical severity of bronchiolitis increased in 2016–2017 and 2017–2018 and changed according to the epidemic seasons only.

Conclusions

Amino acid changes in the hypervariable part of G protein may have altered functions and/or changed its immunogenicity, leading to an impact on disease severity.
Detection of Variants With Reduced Baloxavir Marboxil Susceptibility After Treatment of Children With Influenza A During the 2018–2019 Influenza Season
Authors: Sato Masatoki , Takashita Emi , Katayose Masahiko , Nemoto Kenji , Sakai Nobuko , Hashimoto Koichi , Hosoya Mitsuaki
Published: February 2020

During the 2018–2019 influenza seasons, we detected reduced baloxavir marboxil (baloxavir) susceptible variants with I38S or I38T amino acid substitutions on the PA subunit of influenza virus ribonucleic acid polymerase in 7 of 18 baloxavi-treated children and found that virus titer rebounded in some of these children with variants. We also found fever durations to be similar between patients with or without the variants, but the patients with variants shed the virus 3 days longer and took longer to improve clinical symptoms than those without variants.

The emergence of these variants should be monitored during future influenza seasons.
NUTRITION AND HEALTH: COMPANION ANIMAL APPLICATIONS: Functional nutrition in livestock and companion animals to modulate the immune response
Authors: Bobeck Elizabeth Ann
Published: February 2020

Advances in the understanding of how the immune system functions in response to diet have altered the way we think about feeding livestock and companion animals on both the short (weeks/months) and long-term (years) timelines; however, depth of research in each of these species varies. Work dedicated to understanding how immune function can be altered with diet has revealed additional functions of required nutrients such as vitamins D and E, omega-3 polyunsaturated fatty acids (PUFA), and minerals such as zinc, while feed additives such as phytogenics and probiotics add an additional layer of immunomodulating potential to modern diets. For certain nutrients such as vitamin D or omega-3 PUFA, inclusion above currently recommended levels may optimize immune function and reduce inflammation, while for others such as zinc, additional pharmacological supplementation above requirements may inhibit immune function. Also to consider is the potential to over-immunomodulate, where important functions such as clearance of microbial infections may be reduced when supplementation reduces the inflammatory action of the immune system. Continued work in the area of nutritional immunology will further enhance our understanding of the power of nutrition and diet to improve health in both livestock and companion animals. This review collects examples from several species to highlight the work completed to understand how nutrition can be used to alter immune function, intended or not.
Animal welfare in the U.S. slaughter industry—a focus on fed cattle
Authors: Edwards-Callaway Lily N , Calvo-Lorenzo Michelle S
Published: February 2020

Animal welfare within the U.S. slaughter industry continues to prevail as one of the top priorities for livestock producers, businesses, and consumers alike. There are federal regulations that enforce the humane transport, handling, and slaughter of cattle. The journey that cattle must make to the slaughter facility is comprised of many environmental and human factors that can positively or negatively affect animal welfare. Cattle may be exposed to multiple stressors, such as noise, unfamiliar animals and humans, temperature extremes, temporary food/water deprivation, variable transport distances and experiences, and new pen conditions. The animal caretakers involved in these processes attempt to minimize stress and discomfort for the animals, but research is needed to focus on the gaps in knowledge and to support the implementation of strategies known to enhance the human–animal interactions that occur from farm to slaughter. This literature review will provide a summary of fed cattle welfare topics, research, and industry tools that span across the beef animal’s journey from the farm/feedlot through the slaughter process. In addition, areas that have had little research focus are identified to highlight the need for future work and development of industry tools. Some of these topics include examining trailer design, the use of trailer slats during weather extremes, the welfare aspects of cattle destined for salvage slaughter, multiple preslaughter factors and interactions, abnormal mobility and nonambulatory cattle, lairage environmental conditions, new stunning methods, and the impact of a well-trained, motivated, and stable workforce on cattle and people welfare. The authors conducted a survey at the 2019 North American Meat Institute Animal Care and Handling Conference, which comprised of stakeholders within the meat packing industry, packing plant employees, and food company employees, educators, and auditors. The survey responses identified training/education and communication as areas of need in animal welfare, whereas the majority of survey responses focused on the aspects of the human–animal interaction as the top challenges for the industry. By continuously identifying, measuring, monitoring, and managing animal welfare challenges within the beef cattle slaughter industry, prioritization and execution of programs and training that improve the welfare of cattle can be achieved as animals move through this final stage of the meat production system.
Updating the Bibliography of Interbreeding among Canis in North America
Authors: vonHoldt Bridgett M , Aardema Matthew L
Published: February 2020

This bibliography provides a collection of references that documents the evolution of studies evidencing interbreeding among Canis species in North America. Over the past several decades, advances in biology and genomic technology greatly improved our ability to detect and characterize species interbreeding, which has significance for understanding species in a changing landscape as well as for endangered species management. This bibliography includes a discussion within each category of interbreeding, the timeline of developing evidence, and includes a review of past research conducted on experimental crosses. Research conducted in the early 20th century is rich with detailed records and photographs of hybrid offspring development and behavior. With the progression of molecular methods, studies can estimate historical demographic parameters and detect chromosomal patterns of ancestry. As these methods continue to increase in accessibility, the field will gain a deeper and richer understanding of the evolutionary history of North American Canis.
Bone metastasis of limb segments: Is mesometastasis another poor prognostic factor of cancer patients?
Authors: Tani Shoichiro , Morizaki Yutaka , Uehara Kosuke , Sawada Ryoko , Kobayashi Hiroshi , Shinoda Yusuke , Kawano Hirotaka , Tanaka Sakae
Published: February 2020

Objective

In contrast to acrometastasis, defined as bone metastasis to the hand or foot, the frequency and prognosis of bone metastasis of other limb segments remain unclear. To compare prognosis according to sites of bone metastasis, we defined two new terms in this study: ‘mesometastasis’ and ‘rhizometastasis’ as bone metastasis of ‘forearm or lower leg’ and ‘arm or thigh’, respectively.

Methods

A total of 539 patients who were registered to the bone metastasis database of The University of Tokyo Hospital from April 2012 to May 2016 were retrospectively surveyed. All patients who were diagnosed to have bone metastases in our hospital are registered to the database. Patients were categorized into four groups according to the most distal site of bone metastases: ‘acrometastasis’, ‘mesometastasis’, ‘rhizometastasis’ and ‘body trunk metastasis’.

Results

The frequency of rhizometastasis (22.5%) or body trunk metastasis (73.1%) was significantly higher than that of acrometastasis (2.0%) or mesometastasis (2.4%). The median survival time after diagnosis of bone metastases for each group was as follows: 6.5 months in acrometastasis, 4.0 months in mesometastasis, 16 months in rhizometastasis, 17 months in body trunk metastasis and 16 months overall. In survival curve, there was a statistically significant difference between mesometastasis and body trunk metastasis.

Conclusions

Our findings suggest that ‘mesometastasis’ could be another poor prognostic factor in cancer patients and that patients with mesometastasis should receive appropriate treatments according to their expected prognosis.
Regulatory changes after the enforcement of the new Clinical Trials Act in Japan
Authors: Nakamura Kenichi , Shibata Taro
Published: February 2020

Objective

To describe changes in Japanese clinical trial regulations after the implementation of the Clinical Trials Act in April 2018.

Methods

First, how to apply multiple regulations after the enforcement of Clinical Trials Act was described. Second, the changes in the number of clinical trials in the National Cancer Center Hospital under each regulation were compared before and after the implementation of Clinical Trials Act. Third, new requirements imposed by Clinical Trials Act and their influences were discussed.

Results

In April 2018, Clinical Trials Act was enacted and academic clinical trials were classified into the following three categories: (i) investigator-initiated registration-directed trial under the Pharmaceuticals and Medical Devices Act; (ii) clinical trial under Clinical Trials Act; and (iii) clinical trial under the Ethical Guidelines. While 90% (205/227) of interventional studies were conducted under the Ethical Guidelines before the implementation of Clinical Trials Act in 2018, 46% (94/204) were subject to Clinical Trials Act in 2019 at the National Cancer Center Hospital. Under the Clinical Trials Act, investigators receive a scientific/ethical review by a certified review board (CRB). The identification of investigators in charge is mandated and they are required to submit the conflict of interest management plan to CRB. After the CRB review, the principal investigator must submit the trial plan to the government, and the content is uploaded to the newly established clinical trial registry site, the Japan Registry of Clinical Trials.

Conclusions

The enforcement of the new Clinical Trials Act was supposed to improve the reliability of academic clinical trials in Japan; however, the financial and administrative burden may reduce clinical trial activity in the years to come.
Fabry Disease With Concomitant Lewy Body Disease
Authors: Del Tredici Kelly , Ludolph Albert C , Feldengut Simone , Jacob Christian , Reichmann Heinz , Bohl Jürgen R , Braak Heiko
Published: February 2020

Although Gaucher disease can be accompanied by Lewy pathology (LP) and extrapyramidal symptoms, it is unknown if LP exists in Fabry disease (FD), another progressive multisystem lysosomal storage disorder. We aimed to elucidate the distribution patterns of FD-related inclusions and LP in the brain of a 58-year-old cognitively unimpaired male FD patient suffering from predominant hypokinesia. Immunohistochemistry (CD77, α-synuclein, collagen IV) and neuropathological staging were performed on 100-µm sections. Tissue from the enteric or peripheral nervous system was unavailable. As controls, a second cognitively unimpaired 50-year-old male FD patient without LP or motor symptoms and 3 age-matched individuals were examined. Inclusion body pathology was semiquantitatively evaluated. Although Lewy neurites/bodies were not present in the 50-year-old individual or in controls, severe neuronal loss in the substantia nigra pars compacta and LP corresponding to neuropathological stage 4 of Parkinson disease was seen in the 58-year-old FD patient. Major cerebrovascular lesions and/or additional pathologies were absent in this individual. We conclude that Lewy body disease with parkinsonism can occur within the context of FD. Further studies determining the frequencies of both inclusion pathologies in large autopsy-controlled FD cohorts could help clarify the implications of both lesions for disease pathogenesis, potential spreading mechanisms, and therapeutic interventions.
A unique case of a double common bile duct with ectopic drainage into the gastric antrum: a case report and review of the literature on double duct variants
Authors: Kuan Li Lian , Isherwood John , Pollard Cristina , Dennison Ashley
Published: February 2020

Variants of hepatic duct anomalies are widely discussed in the literature. Duplication producing a double and/or aberrant extrahepatic bile duct is one of the rarest congenital variants that have been sparingly reported. A 71-year-old female presented with right-sided abdominal pain. Computerized tomography demonstrated an enhancing soft tissue thickening in the gastric pylorus with extension into the left lobe of the liver and invasion of the left intrahepatic bile ducts and dilatation of the left intra- and extrahepatic biliary tract. Further examination led to a diagnosis of a double common bile duct with ectopic drainage into the gastric antrum. Recognition of this rare anomaly is of great importance because of the implications in respect of concomitant pathology, the potential short- and long-term sequelae and crucially for operative planning. Failing to appreciate the extent of anomalies may result in significant complications with the attendant morbidity.
The plant MBF1 protein family: a bridge between stress and transcription
Authors: Jaimes-Miranda Fabiola , Chávez Montes Ricardo A
Published: February 2020

The Multiprotein Bridging Factor 1 (MBF1) proteins are transcription co-factors whose molecular function is to form a bridge between transcription factors and the basal machinery of transcription. MBF1s are present in most archaea and all eukaryotes, and numerous reports show that they are involved in developmental processes and in stress responses. In this review we summarize almost three decades of research on the plant MBF1 family, which has mainly focused on their role in abiotic stress responses, in particular the heat stress response. However, despite the amount of information available, there are still many questions that remain about how plant MBF1 genes, transcripts, and proteins respond to stress, and how they in turn modulate stress response transcriptional pathways.
Use of Lean Six Sigma to Improve Access to Care in a Surgical Subspecialty Clinic
Authors: Flanary James T , Rocco Nicholas R , Dougherty Timothy , Christman Matthew S
Published: February 2020

Introduction

At the Naval Medical Center San Diego urology clinic, patients reported waiting for greater than 1 month for an initial consult. A Lean Six Sigma approach was used to improve access to care (ATC) and decrease variation in access by improving scheduling.

Methods

A Define-Measure-Analyze-Improve-Control approach was used. Delay to new patient visits was identified as the focus of intervention. The scheduling template was changed from a fixed stream to a modified wave based on simulation software analysis of appointment cycle times. Appointment length was adjusted based on cycle time analysis, and two rooms per clinician were used instead of one. The ratio of initial consults relative to established follow-ups and procedures was adjusted upward to better balance with the historic demand.

Results

Statistically significant improvement was seen in ATC and compliance with the Defense Health Agency (DHA) standard that new consults be seen within 28 days. Average days for a new consult to be seen were reduced by 7.2 days in the pediatric urology clinic (P < 0.0001) and 6.4 days in the adult urology clinic (P < 0.0001). Compliance with the Defense Health Agency 28-day ATC standard increased from a baseline of 69.2% to 88.9% and 61.7% to 84.4%, respectively, in the pediatric and adult clinics (P < 0.001 for both). Patient satisfaction was maintained at or above the goal threshold throughout the project.

Conclusions

An Lean Six Sigma model was used to improve timeliness of care for our patients, improving the overall quality of their healthcare experience. Simulation software can be used to model the clinic throughput and test alternative scheduling templates. ATC was significantly improved and patient satisfaction was maintained at or above goal thresholds.
Arp 70: an interacting galaxy with extreme outflows
Authors: Camps-Fariña A , Beckman J E , Font J , del Moral-Castro I , Sanchez S F , Borlaff A
Published: February 2020

We analysed a Fabry–Pérot (FP) cube of the interacting pair of galaxies Arp 70, which was obtained from the CeSAM public repository of FP data. On the larger galaxy Arp 70b, we detected the spectral signature of two different outflows, one located in the centre and the other associated with a giant H ii region in the arm region. The central outflow is especially prominent, with the flux of the secondary peaks in the emission-line profiles due to the outflowing gas being similar to that of the main peak. We used an archive fibre spectrum from SDSS to confirm this detection in H α as well as in the [N ii] line and, in addition, to perform diagnostics on the nature of the ionization. The emission at the centre is consistent with a low-ionization nuclear emission-line region and a weak active galactic nucleus. Using the spatial distribution of the profiles in the FP cube, we estimated the shape of the outflow which is consistent with two cones of expanding material, one approaching and the other receding from us, and used this to estimate the physical parameters of the outflow, finding energies of order 1057 erg and masses of order 108 M⊙. On the giant H ii region, we found a very large expanding superbubble with a diameter of ∼5 kpc. The bubble has an energy of order 1054 erg and a mass of about 4 × 107 M⊙. We discuss the possible origins for both of these features and whether they could be associated with the interaction between the galaxies.