bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum 25 Hydroxy Vitamin D Levels in Very Low Birth Weight Infants Receiving Oral Vitamin D Supplementation
Authors: Munshi Upender K. , Graziano Pauline D. , Meunier Kara , Ludke Jennifer , Rios Angel
Published: November 2017

Background and Objective:

Vitamin D supplementation in preterm infants has been recommended by American Academy of Pediatrics (AAP); however, its efficacy and safety has not been well studied. To study 25‐hydroxy vitamin D (25OHD) levels as a marker of vitamin D status of very low birth weight infants while on vitamin D supplementation during neonatal intensive care unit hospitalization.

Methods:

Retrospective study of preterm infants with birth weight <1500 g admitted to our unit from January 2013 to December 2015 who were on oral vitamin D3 400 IU supplementation. Serum 25OHD level were checked at 4, 8, and 12 weeks of age or before discharge and the levels were stratified as deficient <20 ng/mL, insufficient 20 to 29 ng/mL, normal 30 to 60 ng/mL, high 61 to 100 ng/mL and very high >100 ng/mL.

Results:

A total of 301 infants were enrolled, 186 very low birth weight (VLBW; 1000–1499 g) infants and 115 extremely low birth weight (ELBW; <1000 g) infants. Approximately 80% of both VLBWs and ELBWs had deficient or insufficient 25OHD levels at 4 weeks of age. On oral vitamin D supplementation, VLBW infants increased their 25OHD levels significantly by 8 and 12 weeks of age, whereas ELBW infants lagged behind at 8 weeks and increased their 25OHD levels by 12 weeks of age.

Conclusions:

Eighty percent of ELBW and VLBW infants have either deficient or insufficient vitamin D status at 4 weeks of age. Vitamin D supplementation helps in improving the vitamin D levels, VLBW infants significantly more than ELBW infants. AAP recommendation appears to be safe; however, if using higher supplement dosing, 25OHD level should be monitored to avoid high and very high vitamin D levels.
Association of Response to Inhaled Nitric Oxide and Duration of Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome*
Authors: Dowell Jasmine C. , Thomas Neal J. , Yehya Nadir
Published: November 2017

Objectives:

Literature regarding appropriate use of inhaled nitric oxide for pediatric acute respiratory distress syndrome is sparse. This study aims to determine if positive response to inhaled nitric oxide is associated with decreased mortality and duration of mechanical ventilation in pediatric acute respiratory distress syndrome.

Design:

Retrospective cohort study.

Setting:

Large pediatric academic medical center.

Patients or Subjects:

One hundred sixty-one children with pediatric acute respiratory distress syndrome and inhaled nitric oxide exposure for greater than or equal to 1 hour within 3 days of pediatric acute respiratory distress syndrome onset.

Interventions:

Patients with greater than or equal to 20% improvement in oxygenation index or oxygen saturation index by 6 hours after inhaled nitric oxide initiation were classified as “responders.”

Measurements and Main Results:

Oxygenation index, oxygen saturation index, and ventilator settings were evaluated prior to inhaled nitric oxide initiation and 1, 6, 12, and 24 hours following inhaled nitric oxide initiation. Primary outcomes were mortality and duration of mechanical ventilation. Baseline characteristics, including severity of illness, were similar between responders and nonresponders. Univariate analysis showed no difference in mortality between responders and nonresponders (21% vs 21%; p = 0.999). Ventilator days were significantly lower in responders (10 vs 16; p < 0.001). Competing risk regression (competing risk of death) confirmed association between inhaled nitric oxide response and successful extubation (subdistribution hazard ratio = 2.11; 95% CI, 1.41–3.17; p < 0.001). Response to inhaled nitric oxide was associated with decreased utilization of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation and lower hospital charges (difference in medians of $424,000).

Conclusions:

Positive response to inhaled nitric oxide was associated with fewer ventilator days, without change in mortality, potentially via reduced use of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation. Future studies of inhaled nitric oxide for pediatric acute respiratory distress syndrome should stratify based on oxygenation response, given the association with favorable outcomes.
Previous Looks May Be Deceiving
Authors: Woll Christopher , Chen Lei
Published: November 2017

We describe a case of a 17-year-old boy presenting to the emergency department following a presyncopal episode with exertion. His medical history is significant for a murmur, which was determined to be benign in nature after a normal echocardiogram at 12 years of age. His workup in the emergency department included an electrocardiogram, which was significant for left ventricular hypertrophy, and a point-of-care ultrasound, which was significant for severe concentric left ventricular hypertrophy with diastolic dysfunction consistent with hypertrophic cardiomyopathy.
A Rare Case of Infantile Myofibromatosis Presenting to the Emergency Department as Undiagnosed Long Bone Fractures
Authors: McGuire Melissa A. , Hendry Phyllis L. , Hong Nancy
Published: November 2017

Infantile myofibromatosis is a disorder of mesenchymal tumors that usually presents within the first 2 years of life. Most patients initially present because of the presence of visible or palpable subcutaneous tumors. We report a case of a fussy 5-week-old infant who presented to an emergency department with bilateral femur fractures initially thought to be due to nonaccidental trauma or a metabolic bone disorder. She was ultimately diagnosed after admission with infantile myofibromatosis after taking an extensive family history and after further laboratory and radiologic evaluation. There are no previously published cases of undiagnosed infantile myofibromatosis presenting to the emergency department, especially with multiple long bone fractures.
Succession Planning in State Health Agencies in the United States: A Brief Report
Authors: Harper Elizabeth , Leider Jonathon P. , Coronado Fatima , Beck Angela J.
Published: November 2017

Objective:

Approximately 25% of the public health workforce plans to retire by 2020. Succession planning is a core capability of the governmental public health enterprise; however, limited data are available regarding these efforts in state health agencies (SHAs).

Methods:

We analyzed 2016 Workforce Gaps Survey data regarding succession planning in SHAs using the US Office of Personnel Management's (OPM's) succession planning model, including 6 domains and 27 activities. Descriptive statistics were calculated for all 41 responding SHAs.

Results:

On average, SHAs self-reported adequately addressing 11 of 27 succession planning activities, with 93% of SHAs adequately addressing 1 or more activities and 61% adequately addressing 1 or more activities in each domain.

Conclusions:

The majority of OPM-recommended succession planning activities are not being addressed, and limited succession planning occurs across SHAs. Greater activity in the OPM-identified succession planning domains may help SHAs contend with significant turnover and better preserve institutional knowledge.
How Can Safer Care Be Achieved? Patient Safety Officers’ Perceptions of Factors Influencing Patient Safety in Sweden
Authors: Ridelberg Mikaela , Roback Kerstin , Nilsen Per
Published: November 2017

Objective

This study aimed to survey health care professionals in Sweden on the factors that they believe have been most important in reaching the current level of patient safety and achieving safer care in the future as well as the characteristics of the county councils that have been the most successful in achieving safe care.

Methods

The study population consisted of 222 patient safety officers, that is, health care professionals with strategic positions in patient safety work in the county councils. A postal questionnaire was used for data collection.

Results

The survey response rate was 70%. The factors that were considered most important for the current level of patient safety were efforts to reduce the use of antibiotics; Swedish patient safety law; and internal discussions with the county council management, heads of health care units, health care providers, and so on. The factors that were considered most important to achieve safer care in the future were improved communication between health care practitioners and patients, improved organizational culture, improved communication, and patient safety knowledge as a compulsory component of basic education for health care practitioners.

Conclusions

Several factors rated highly for achieving the current level of patient safety are part of the government-supported financial incentive plan. Patient safety is attributed to a broad range of factors, and many solutions might contribute to improved patient safety in the future. The most successful county councils are characterized by leadership support for patient safety, well-organized patient safety work, long-term commitment to patient safety, and an organizational culture that is conducive to patient safety.
Dentists Survey on Adverse Events During Their Clinical Training
Authors: Osegueda-Espinosa Alfredo Alan , Sánchez-Pérez Leonor , Perea-Pérez Bernardo , Labajo-González Elena , Acosta-Gio A. Enrique
Published: November 2017

Background

Adverse events (AEs) begin challenging the safe practice of dentistry early when students start treating patients at dental school. We assessed the frequency with which dentists caused common AEs during their undergraduate clinical training.

Methods

A convenience sample of dentists, graduated from more than 34 dental schools in Mexico and other Spanish speaking countries, answered a confidential, self-administered questionnaire with closed-format questions on common AEs they caused and their active errors that could have led to AEs in the teaching clinics.

Results

Of 207 participants, 80% had graduated recently. As undergraduates, 79% caused AEs; 38% admitted to causing one adverse event, 41% to causing two or more, and 36% committed active errors that could have hurt patients. No significant associations between AEs and sex or type of school were observed.

Conclusions

The results indicate that dental students caused AEs or committed errors that placed patients at risk, during their clinical training.

Practical Implications

Dental schools must identify challenges to patient safety at their teaching clinics and introduce risk reduction strategies to protect their patients and foster a safety culture in dental education.
Anastomotic Leak Does Not Impact Oncologic Outcomes After Preoperative Chemoradiotherapy and Resection for Rectal Cancer
Authors: Jang Jae Hyuck , Kim Hee Cheol , Huh Jung Wook , Park Yoon Ah , Cho Yong Beom , Yun Seong Hyeon , Lee Woo Yong , Yu Jeong Il , Park Hee Chul , Park Young Suk , Park Joon Oh
Published: November 2017

Objective:

The aim of this study was to evaluate the relationship of anastomotic leakage, local recurrence, and overall survival in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection.

Background:

Little is known about the association between anastomotic leakage and oncologic outcomes after preoperative CRT.

Methods:

A total of 698 consecutive primary rectal cancer patients after preoperative CRT between April 19, 2000, and December 27, 2013, were retrospectively reviewed. Forty-seven patients who had anastomotic leakage were compared with 651 patients who had no anastomotic leakage.

Results:

Of 698 patients, 47 (6.7%) patients had anastomotic leakage. Among these 47 patients, 39 (83.0%) had grade C leak that required urgent operation, while 8 (17.0%) had grade B leak that was managed expectantly or by percutaneous drainage. The median follow-up period was 47.6 months (range, 27.1 to 68.9 months). One hundred twenty (17.2%) recurrences were identified among all patients. The median overall disease-free survival was 43 months (range, 22.4 to 66.7 months). Five-year disease-free survival did not differ significantly between the 2 groups (80.5% vs 80.4%, P = 0.839). Five-year local recurrence-free survival did not differ significantly either between the 2 groups (93.7% vs 94.9%, P = 0.653). Five-year overall survival rates of patients with or without leakage were 90.9% and 86.3%, respectively (P = 0.242). Five-year cancer-specific survival rates of patients with or without leakage were 92.2% and 86.3%, respectively (P = 0.248).

Conclusion:

After preoperative CRT, an anastomotic leak is not associated with a significant increase in local recurrence or long-term survival in rectal cancer.
One-Year Outcomes of a Cohort of Renal Transplant Patients Related to BMI in a Steroid-Sparing Regimen
Authors: Bellini Maria Irene , Koutroutsos Kostas , Galliford Jack , Herbert Paul E.
Published: November 2017

Background

The prevalence of overweight and obese kidney transplant recipients (KTR) has risen in parallel to the obesity epidemic that has affected the general population over the last two decades. At present, there is an ongoing debate regarding the suitability for transplantation of obese patients.

Methods

Data were prospectively collected on consecutive single organ KTR transplanted between January 2014 and March 2016. The patients were stratified according to their body mass index (BMI) using the World Health Organization classification. As a measure of allograft function Modification of Diet in Renal Disease, estimated glomerular filtration rate was used at 3, 6, and 12 months posttransplant.

Results

We included 370 KTR: 126 of 370 women; median age, 52.7 years (range, 19-77 years), followed up for a median of 19.5 ± 8.6 months. In total, 155 (41.9%) KTR were underweight or of normal BMI at transplant, whereas 148 (40%) were overweight, and 67 (18.1%) were classified as obese (47 [12.7%] class 1, 11 [3%] class 2, 9 [2.4%] class 3). Overweight and obese KTR had a higher incidence of pretransplant diabetes (P = 0.021), but no difference was found in new-onset hyperglycemia posttransplant (P = 0.35). There was also no difference in posttransplant hospital length of stay (P = 0.386). Obese and overweight KTR had a significantly lower estimated glomerular filtration rate than underweight and normal BMI KTR at 3 and 6 months posttransplant, a finding that did not persist at 1 year follow-up. Overall, 23 patients lost their grafts, and 20 patients died during follow-up. Kaplan Meier analysis showed no difference in allograft loss between the different BMI groups (log rank P = 0.7).

Conclusions

In this single-center study, which used short-term data, overweight and obese patients were shown not to have inferior outcomes regarding renal function 1 year posttransplant.
Genome sequence analysis of emm89 Streptococcus pyogenes strains causing infections in Scotland, 2010–2016
Authors: Beres Stephen B. , Olsen Randall J. , Ojeda Saavedra Matthew , Ure Roisin , Reynolds Arlene , Lindsay Diane S. J. , Smith Andrew J. , Musser James M.
Published: November 2017

Purpose. Strains of type emm89 Streptococcus pyogenes have recently increased in frequency as a cause of human infections in several countries in Europe and North America. This increase has been molecular epidemiologically linked with the emergence of a new genetically distinct clone, designated clade 3. We sought to extend our understanding of this epidemic behavior by the genetic characterization of type emm89 strains responsible in recent years for an increased frequency of infections in Scotland.

Methodology. We sequenced the genomes of a retrospective cohort of 122 emm89 strains recovered from patients with invasive and noninvasive infections throughout Scotland during 2010 to 2016.

Results. All but one of the 122 emm89 infection isolates are of the recently emerged epidemic clade 3 clonal lineage. The Scotland isolates are closely related to and not genetically distinct from recent emm89 strains from England, they constitute a single genetic population.

Conclusions. The clade 3 clone causes virtually all-contemporary emm89 infections in Scotland. These findings add Scotland to a growing list of countries of Europe and North America where, by whole genome sequencing, emm89 clade 3 strains have been demonstrated to be the cause of an ongoing epidemic of invasive infections and to be genetically related due to descent from a recent common progenitor.
Two C++ Libraries for Counting Trees on a Phylogenetic Terrace
Authors: Biczok R. , Bozsoky P. , Eisenmann P. , Ernst J. , Ribizel T. , Scholz F. , Trefzer A. , Weber F. , Hamann M. , Stamatakis A.
Published: November 2017

Motivation

The presence of terraces in phylogenetic tree space, that is, a potentially large number of distinct tree topologies that have exactly the same analytical likelihood score, was first described by Sanderson et al, (2011). However, popular software tools for maximum likelihood and Bayesian phylogenetic inference do not yet routinely report, if inferred phylogenies reside on a terrace, or not. We believe, this is due to the unavailability of an efficient library implementation to (i) determine if a tree resides on a terrace, (ii) calculate how many trees reside on a terrace, and (iii) enumerate all trees on a terrace.

Results

In our bioinformatics programming practical we developed two efficient and independent C++ implementations of the SUPERB algorithm by Constantinescu and Sankoff (1995) for counting and enumerating the trees on a terrace. Both implementations yield exactly the same results and are more than one order of magnitude faster and require one order of magnitude less memory than a previous 3rd party python implementation.

Availability

The source codes are available under GNU GPL at https://github.com/terraphast

Contact

Alexandros.Stamatakis@h-its.org
No kissing in the nucleus: Unbiased analysis reveals no evidence of trans chromosomal regulation of mammalian immune development
Authors: Johanson Timothy M. , Coughlan Hannah D. , Lun Aaron T.L. , Bediaga Naiara G. , Naselli Gaetano , Garnham Alexandra L. , Harrison Leonard C. , Smyth Gordon K. , Allan Rhys S.
Published: November 2017

It has been proposed that interactions between mammalian chromosomes, or transchromosomal interactions (also known as kissing chromosomes), regulate gene expression and cell fate determination. Here we aimed to identify novel transchromosomal interactions in immune cells by high-resolution genome-wide chromosome conformation capture. Although we readily identified stable interactions incis,and also between centromeres and telomeres on different chromosomes, surprisingly we identified no gene regulatory transchromosomal interactions in either mouse or human cells, including previously described interactions. We suggest that advances in the chromosome conformation capture technique and the unbiased nature of this approach allow more reliable capture of interactions between chromosomes than previous methods. Overall our findings suggest that stable transchromosomal interactions that regulate gene expression are not present in mammalian immune cells and that lineage identity is governed bycis,nottranschromosomal interactions.
Neurogenic decisions require a cell cycle independent function of the CD25B phosphatase
Authors: Bonnet Frédéric , Roussat Mélanie , Molina Angie , Azais Manon , Belvialar Sophie , Gautrais Jacques , Pituello Fabienne , Agius Eric
Published: November 2017

A fundamental issue in developmental biology and in organ homeostasis is understanding the molecular mechanisms governing the balance between stem cell maintenance and differentiation into a specific lineage. Accumulating data suggest that cell cycle dynamics plays a major role in the regulation of this balance. Here we show that the G2/M cell cycle regulator CDC25B phosphatase is required in mammals to finely tune neuronal production in the neural tube. We show that in chick neural progenitors, CDC25B activity is both required and sufficient to stimulate neurogenic divisions and to promote neuronal differentiation. We design a mathematical model showing that within a limited period of time, cell cycle length modifications cannot account for changes in the ratio of the mode of division. Using a CDC25B point mutation that cannot interact with CDK, we show that part of CDC25B activity on neurogenic divisions is independent of its action on the cell cycle.
Diversity, stability, and reproducibility in stochastically assembled microbial ecosystems
Authors: Goyal Akshit , Maslov Sergei
Published: November 2017

Microbial ecosystems are remarkably diverse, stable, and often consist of a balanced mixture of core and peripheral species. Here we propose a conceptual model exhibiting all these emergent properties in quantitative agreement with real ecosystem data, specifically species abundance and prevalence distributions. Resource competition and metabolic commensalism drive stochastic ecosystem assembly in our model. We demonstrate that even when supplied with just one resource, ecosystems can exhibit high diversity, increasing stability, and partial reproducibility between samples.
ModellingG×Ewith historical weather information improves genomic prediction in new environments
Authors: Gillberg Jussi , Marttinen Pekka , Mamitsuka Hiroshi , Kaski Samuel
Published: November 2017

Interaction between the genotype and the environment (G×E) has a strong impact on the yield of major crop plants. Although influential, takingG×Eexplictily into account in plant breeding has remained difficult. RecentlyG×Ehas been predicted from environmental and genomic covariates, but existing works have not shown that generalization to new environments and years without access to in-season data is possible and practical applicability remains unclear. Using data from a Barley breeding program in Finland, we construct an in-silico experiment to study the viability ofG×Eprediction under practical constraints. We show that the response to the environment of a new generation of untested Barley cultivars can be predicted in new locations and years using genomic data, machine learning and historical weather observations for the new locations. Our results highlight the need for models ofG×E: non-linear effects clearly dominate linear ones and the interaction between the soil type and daily rain is identified as the main driver forG×Efor Barley in Finland. Our study implies that genomic selection can be used to capture the yield potential inG×Eeffects for future growth seasons, providing a possible means to achieve yield improvements, needed for feeding the growing population.
Bottom-up and top-down control of dispersal across major organismal groups: a coordinated distributed experiment
Authors: Fronhofer Emanuel A. , Legrand Delphine , Altermatt Florian , Ansart Armelle , Blanchet Simon , Bonte Dries , Chaine Alexis , Dahirel Maxime , De Laender Frederik , De Raedt Jonathan , di Gesu Lucie , Jacob Staffan , Kaltz Oliver , Laurent Estelle , Little Chelsea J. , Madec Luc , Manzi Florent , Masier Stefano , Pellerin Felix , Pennekamp Frank , Schtickzelle Nicolas , Therry Lieven , Vong Alexandre , Winandy Laurane , Cote Julien
Published: November 2017

Organisms rarely experience a homogeneous environment. Rather, ecological and evolutionary dynamics unfold in spatially structured and fragmented landscapes, with dispersal as the central process linking these dynamics across spatial scales. Because dispersal is a multi-causal and highly plastic life-history trait, finding general drivers that are of importance across species is challenging but highly relevant for ecological forecasting.

We here tested whether two fundamental ecological forces and main determinants of local population dynamics, top-down and bottom-up control, generally explain dispersal in spatially structured communities. In a coordinated distributed experiment spanning a wide range of actively dispersing organisms, from protozoa to vertebrates, we show that bottom-up control, that is resource limitation, consistently increased dispersal. While top-down control, that is predation risk, was an equally important dispersal driver as bottom-up control, its effect depended on prey and predator space use and whether dispersal occurred on land, in water or in the air: species that routinely use more space than their predators showed increased dispersal in response to predation, specifically in aquatic environments. After establishing these general causes of dispersal, we used a metacommunity model to show that bottom-up and top-down control of dispersal has important consequences for local population fluctuations as well as cascading effects on regional metacommunity dynamics. Context-dependent dispersal reduced local population fluctuations and desynchronized dynamics between communities, two effects that increase population and community stability.

Our study provides unprecedented insights into the generality of the positive resource dependency of dispersal as well as a robust experimental test of current theory predicting that predator-induced dispersal is modulated by prey and predator space use. Our experimental and theoretical work highlights the critical importance of the multi-causal nature of dispersal as well as its cascading effects on regional community dynamics, which are specifically relevant to ecological forecasting.
The C-terminal extension landscape of naturally presented HLA-I ligands
Authors: Guillaume Philippe , Picaud Sarah , Baumgaertner Petra , Montandon Nicole , Schmidt Julien , Speiser Daniel E , Coukos George , Bassani-Sternberg Michal , Fillipakopoulos Panagis , Gfeller David
Published: November 2017

HLA-I molecules play a central role in antigen presentation. They typically bind 9- to 12-mer peptides and their canonical binding mode involves anchor residues at the second and last positions of their ligands. To investigate potential non-canonical binding modes we collected in-depth and accurate HLA peptidomics datasets covering 54 HLA-I alleles and developed novel algorithms to analyze these data. Our results reveal frequent (442 unique peptides) and statistically significant C-terminal extensions for at least eight alleles, including the common HLA-A03:01, HLA-A31:01 and HLA-A68:01. High resolution crystal structure of HLA-A68:01 with such a ligand uncovers structural changes taking place to accommodate C-terminal extensions and helps unraveling sequence and structural properties predictive of the presence of these extensions. Scanning viral proteomes with the new C-terminal extension motifs identifies many putative epitopes and we demonstrate direct recognition by human CD8+ T cells of a C-terminally extended epitope from cytomegalovirus.
Ultra-sensitive mutation detection and genome-wide DNA copy number reconstruction by error corrected circulating tumour DNA sequencing
Authors: Mansukhani Sonia , Barber Louise J. , Moorcraft Sing Yu , Davidson Michael , Woolston Andrew , Griffiths Beatrice , Fenwick Kerry , Herman Bram , Matthews Nik , O’Leary Ben , Hulkki Sanna , De Castro David Gonzalez , Hubank Michael , Patel Anisha , Wotherspoon Andrew , Okachi Aleruchi , Rana Isma , Begum Ruwaida , Davies Matthew , Powles Thomas , von Loga Katharina , Turner Nick , Watkins David , Chau Ian , Cunningham David , Starling Naureen , Gerlinger Marco
Published: November 2017

Minimally invasive circulating free DNA (cfDNA) analysis can portray cancer genome landscapes but highly sensitive and specific genetic approaches are necessary to accurately detect mutations with often low variant frequencies. We developed a targeted cfDNA sequencing technology using novel off-the-shelf molecular barcodes for error correction, in combination with custom solution hybrid capture enrichment. Modelling based on cfDNA yields from 58 patients shows that our assay, which requires 25ng of cfDNA input, should be applicable to >95% of patients with metastatic colorectal cancer. Sequencing of a 163.3 kb target region including 32 genes detected 100% of single nucleotide variants with 0.15% variant frequency in cfDNA spike-in experiments. Molecular barcode error correction reduced false positive mutation calls by 98.6%. In a series of 28 patients with metastatic colorectal cancers, 80 out of 91 (88%) mutations previously detected by tumour tissue sequencing were called in the cfDNA. Call rates were similar for single nucleotide variants and small insertions/deletions. Mutations only called in cfDNA but not detectable in matched tumour tissue included, among others, a subclonal resistance driver mutation to anti-EGFR antibodies in theKRASgene, multiple activatingPIK3CAmutations in each of two patients (indicative of parallel evolution), andTP53mutations originating from clonal haematopoiesis. Furthermore, we demonstrate that cfDNA off-target read analysis allows the reconstruction of genome wide copy number aberration profiles from 71% of these 28 cases. This error-corrected ultra-deep cfDNA sequencing assay with a target region that can be readily customized enables broad insights into cancer genomes and evolution.
De Novo Mutations Resolve Disease Transmission Pathways in Clonal Malaria
Authors: Redmond Seth N , MacInnis Bronwyn M , Bopp Selina , Bei Amy K , Ndiaye Daouda , Hartl Daniel L , Wirth Dyann F , Volkman Sarah K , Neafsey Daniel E
Published: November 2017

Detecting de novo mutations in viral and bacterial pathogens enables researchers to reconstruct detailed networks of disease transmission and is a key technique in genomic epidemiology. However these techniques have not yet been applied to the malaria parasite, Plasmodium falciparum, in which a larger genome, slower generation times, and a complex life cycle make them difficult to implement. Here we demonstrate the viability of de novo mutation studies in P. falciparum for the first time. Using a set of clinical samples and novel methods of sequencing, library preparation, and genotyping, we have genotyped low-complexity regions of the genome with a high degree of accuracy. Despite its slower evolutionary rate compared to bacterial or viral species, de novo mutation can be detected in P. falciparum across timescales of just 1-2 years and evolutionary rates in low-complexity regions of the genome can be up to twice that detected in the rest of the genome. The increased mutation rate allows the identification of separate clade expansions that cannot be found using previous genomic epidemiology approaches and could be a crucial tool for mapping residual transmission patterns in disease elimination campaigns and reintroduction scenarios.
EditR: A novel base editing quantification software using Sanger sequencing
Authors: Kluesner Mitchell G. , Nedveck Derek A. , Lahr Walker S. , Garbe John R. , Abrahante Juan E. , Webber Beau R. , Moriarity Branden S.
Published: November 2017

CRISPR/Cas9-Cytidine deaminase fusion enzymes - termed Base Editors – allow targeted editing of genomic deoxcytidine to deoxthymidine (C→T) without the need for double stranded break induction. Base editors represent a paradigm-shift in gene editing technology, due to their unprecedented efficiency to mediate targeted, single-base conversion; however, current analysis of base editing outcomes rely on methods that are either imprecise or expensive and time consuming. To overcome these limitations, we developed a simple, cost effective, and accurate program to measure base editing efficiency from fluorescence-based Sanger sequencing, termed EditR. We provide EditR as a free online tool or downloadable desktop application requiring a single Sanger sequencing file and guide RNA sequence (baseeditr.com). EditR is more accurate than enzymatic assays, and provides added insight to the position, type and efficiency of base editing. Collectively, we demonstrate that EditR is a robust, inexpensive tool that will facilitate the broad application of base editing technology, thereby fostering further innovation in this burgeoning field.
A theory of multineuronal dimensionality, dynamics and measurement
Authors: Gao Peiran , Trautmann Eric , Yu Byron , Santhanam Gopal , Ryu Stephen , Shenoy Krishna , Ganguli Surya
Published: November 2017

In many experiments, neuroscientists tightly control behavior, record many trials, and obtain trial-averaged firing rates from hundreds of neurons in circuits containing billions of behaviorally relevant neurons. Di-mensionality reduction methods reveal a striking simplicity underlying such multi-neuronal data: they can be reduced to a low-dimensional space, and the resulting neural trajectories in this space yield a remarkably insightful dynamical portrait of circuit computation. This simplicity raises profound and timely conceptual questions. What are its origins and its implications for the complexity of neural dynamics? How would the situation change if we recorded more neurons? When, if at all, can we trust dynamical portraits obtained from measuring an infinitesimal fraction of task relevant neurons? We present a theory that answers these questions, and test it using physiological recordings from reaching monkeys. This theory reveals conceptual insights into how task complexity governs both neural dimensionality and accurate recovery of dynamic portraits, thereby providing quantitative guidelines for future large-scale experimental design.
TCGA-Assembler 2: Software Pipeline for Retrieval and Processing of TCGA/CPTAC Data
Authors: Wei Lin , Jin Zhilin , Yang Shengjie , Xu Yanxun , Zhu Yitan , Ji Yuan
Published: November 2017

Motivation

The Cancer Genome Atlas (TCGA) program has produced huge amounts of cancer genomics data providing unprecedented opportunities for research. In 2014, we developed TCGA-Assembler (Zhu et al, 2014), a software pipeline for retrieval and processing of public TCGA data. In 2016, TCGA data were transferred from the TCGA data portal to the Genomic Data Commons (GDC), which is supported by a different set of data storage and retrieval mechanisms. In addition, new proteomics data of TCGA samples have been generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) program, which were not available for downloading through TCGA-Assembler. It is desirable to acquire and integrate data from both GDC and CPTAC.

Results

We develop TCGA-Assembler 2 (TA2) to automatically download and integrate data from GDC and CPTAC. We make substantial improvement on the functionality of TA2 to enhance user experience and software performance. TA2 together with its previous version have helped more than 2,000 researchers from 64 countries to access and utilize TCGA and CPTAC data in their research. Availability of TA2 will continue to allow existing and new users to conduct reproducible research based on TCGA and CPTAC data.

Availability

http://www.compgenome.org/TCGA-Assembler/

Contact

koaeraser@gmail.com or zhuyitan@gmail.com
TNER: A Novel Background Error Suppression Method for Mutation Detection in Circulating Tumor DNA
Authors: Deng Shibing , Lira Maruja , Huang Stephen , Wang Kai , Valdez Crystal , Kinong Jennifer , Rejto Paul A , Bienkowska Jadwiga , Hardwick James , Xie Tao
Published: November 2017

The use of ultra-deep, next generation sequencing of circulating tumor DNA (ctDNA) holds great promise for early detection of cancer as well as a tool for monitoring disease progression and therapeutic responses. However, the low abundance of ctDNA in the bloodstream coupled with technical errors introduced during library construction and sequencing complicates mutation detection. To achieve high accuracy of variant calling via better distinguishing low frequency ctDNA mutations from background errors, we introduce TNER (Tri-Nucleotide Error Reducer), a novel background error suppression method that provides a robust estimation of background noise to reduce sequencing errors. It significantly enhances the specificity for downstream ctDNA mutation detection without sacrificing sensitivity. Results on both simulated and real healthy subjects’ data demonstrate that the proposed algorithm consistently outperforms a current, state of the art, position-specific error polishing model, particularly when the sample size of healthy subjects is small. TNER is publicly available at https://github.com/ctDNA/TNER.
Crystal structure of the formal 20 electron zirconocene pentafulvene complex Cp2Zr(η5,η1-adamantylidenepentafulvene):toluene:n-hexane = 1:0.125:0.125
Authors: Fischer Malte , Schmidtmann Marc , Beckhaus Rüdiger
Published: November 2017

The crystal structure of a solvated zirconocene pentafulvene complex with a bulky adamantylidene substitution pattern, namely (η5,η1-adamantylidenepentafulvene)bis(η5-cyclopentadienyl)zirconium(IV)–toluene–n-hexane (8/1/1), [Zr(C15H18)(C5H5)2]·0.125C7H8·0.125C6H14, is reported. Reducing zirconocene dichloride with magnesium results in the formation of a low-valent zirconocene reagent that reacts readily with adamantylidenepentafulvene to give the aforementioned complex. Single crystal X-ray diffraction proves the dianion-like η5:η1binding mode of the fulvene ligand to the central ZrIVatom. The asymmetric unit contains four independent molecules of [η5:η1-adamantylidenepentafulvene]bis[(η5)-cyclopentadienyl]zirconium(IV), together with half a molecule of toluene disordered with half a molecule ofn-hexane (the solvent molecules have no direct influence on the complex). In each of the four complex molecules, the central ZrIVatom has a distorted tetrahedral coordination environment. The measured crystal consisted of two domains with a refined ratio of 0.77:0.23.
Participation and Chinese non-government organization accountability
Authors: Zhong Ling , Fisher Karen R.
Published: November 2017

Purpose

As transition countries shift to a mixed welfare system, the accountability of non-government organizations (NGOs) becomes critical to quality services. Yet, poor financial and managerial practices of some NGOs in China have led to distrust from citizens. The purpose of this paper is to use a democratic accountability framework to examine citizen participation in NGOs as an approach to understand an angle of this distrust. Does the Chinese language academic literature about NGO accountability engage with concepts of participation in NGO governance, management and service use?

Design/methodology/approach

The method was content analysis of a search of words and concepts relating to NGOs, participation and accountability in the available Chinese language literature on NGO accountability through the newly developed search engine Wenjin Search of the National Library of China.

Findings

The analysis found that most Chinese literature only emphasizes problems of accountability, causes and regulatory solutions. When the literature includes participation, it refers to it as a platform for civil society, rather than a process of accountability within an NGO.

Research limitations/implications

Searching by keywords in one search engine may not be exhaustive. The results probably reflect most of the current research of Chinese scholars, considering the depth of the search engine.

Practical implications

Formal NGOs are relatively new in the Chinese political landscape; and government regulations are largely administrative and unenforced. At conceptual and political levels, the absence of discussion about other forms of accountability ignores questions about public dissatisfaction with NGO performance and the public’s willingness to contribute to NGO effectiveness, and civic engagement.

Originality/value

An implication is that until Chinese NGO research also incorporates democratic accountability concepts, it will continue to ignore the internal and external drivers from citizens for NGO change. Transition country NGOs that encourage participation have the potential to engender greater accountability in the organization, community and in state relations.
GoodYarn: building mental health literacy in New Zealand’s rural workforce
Authors: Morgaine Kate , Thompson Louise , Jahnke Katie , Llewellyn Rebecca
Published: November 2017

Purpose

“GoodYarn” is a skills-based workshop that focusses on building mental health literacy in rural communities, members of which are known to experience geographic, attitudinal and service configuration barriers to accessing mental health services. The purpose of this paper is to evaluate the impact of the GoodYarn project on raising mental health literacy in the rural community.

Design/methodology/approach

GoodYarn is primarily for farmers, their families and farm workers, as well as the “farmer facing” workforce. The focus on mental health literacy aligns with the mental health promotion approach of using methods that foster supportive environments. By raising the mental health literacy of those not directly needing help, but in positions to help those that do – such as employers, rural professionals and rural support industries who are well placed to perceive stressors in farmers – GoodYarn builds a community with the knowledge and skills to identify and approach those experiencing mental distress or illness, and direct them to appropriate support and services. All participants in the GoodYarn workshops (n=430) were invited to complete a questionnaire at the end of the workshop. All participants answered the questionnaire, with over 80 per cent answering all questions.

Findings

Participant feedback affirmed the utility of GoodYarn as an effective vehicle to facilitate the discussion of mental illness in rural farming communities of New Zealand. GoodYarn had a significant positive impact on the three immediate workshop indicators of awareness, confidence and knowledge (p<0.001 for all three indicators). Further, the high level of concordance in workshop outcomes across various organisations’ delivery indicates programme consistency and quality has been maintained throughout the upscaling of the programme.

Originality/value

The uptake of the GoodYarn programme by rural organisations and communities at a national level, and the positive evaluation results, provide encouragement that building mental health literacy in the rural workforce is a promising mental health promotion strategy.
Social entrepreneurship: the role of national leadership culture
Authors: Coker Kesha K. , Flight Richard L. , Valle Kelly N.
Published: November 2017

Purpose

Social entrepreneurship has emerged as an important realm of entrepreneurship during the last decade. Research on what motivates social entrepreneurial activity continues to be of interest in the field. Given the integral role of the social entrepreneur, one area identified as deserving more attention is the leadership traits of the social entrepreneur. This paper addresses this gap by presenting a conceptual model on the role of national leadership culture on social entrepreneurship.

Design/methodology/approach

As part of the social fabric of a country, national leadership culture is viewed as a social contextual factor that can either enhance or hinder social entrepreneurial activity. As its broader conceptual base, this paper relies on institutional theory, marketing systems and leadership theory. At the heart of the proposed conceptual model are six leadership dimensions from the Global Leadership and Organizational Behavior Effectiveness (GLOBE) theoretical model: charismatic/value-based, team-oriented, participative, self-protective, humane-oriented and autonomous. These leadership dimensions are central to the propositions that accompany the proposed conceptual model.

Findings

Implications of this research for entrepreneurial marketing and public policy are presented. Since this research is conjectural, future directions for empirical research on national leadership culture in social entrepreneurship are discussed.

Originality/value

The conceptual model is the first to examine the role of national leadership culture on social entrepreneurship. The research adds value to the growing body of research on social entrepreneurship in its social context. It answers the call in the literature to examine leadership as it pertains to the individual entrepreneur’s pre-disposition to engage in social entrepreneurial activity.
Dynamic capabilities in aged care service innovation: the role of social assistive technologies and consumer-directed care strategy
Authors: Khaksar Seyed Mohammad Sadegh , Shahmehr Fatemeh S. , Khosla Rajiv , Chu Mei Tai
Published: November 2017

Purpose

By developing a conceptual model, the purpose of this paper is to improve the understanding of the role of social assistive technologies in facilitating the process of service innovation in care providing organisations to adopt the principles of the consumer-directed care strategy and reduce perceived consumer vulnerability.

Design/methodology/approach

Using a cross-sectional survey method, the authors collected data through a survey questionnaire distributed among 335 aged caregivers and specialists. The conceptual model and its 11 research hypotheses were examined using confirmatory factor analysis in structural equation modelling. The rival and mediation models were also estimated.

Findings

The conceptual model was validated and eight of eleven hypotheses were supported. It was found that dynamic capabilities are crucial to developing service innovation concept in care providing organisations. In this way, social assistive technologies play a facilitating role to promote the consumer-directed care strategy throughout care providing organisations and allow care providers to enhance wellbeing of vulnerable older people based on their socio-economic status. From the lens of aged care providers, it was also found that the consumer-directed care strategy implemented in aged care facilities may help reduce consumer vulnerability among older people especially when they use social assistive technologies in their service settings.

Practical implications

This study suggests aged care service providers should boost dynamic service innovation capabilities to improve the need for social assistive technologies in aged care facilities with respect to the importance of the consumer-directed care strategy.

Originality/value

This study contributes to the development and validation of a conceptual model for the use of social assistive technologies to sustain service innovation in aged care business models and enhance the consumer-directed care strategy’s performance to better understand consumer vulnerability among older people.
Helpless helpers: primary care therapist self-efficacy working with intimate partner violence and ageing women
Authors: Watson Carlie , Carthy Nikki , Becker Sue
Published: November 2017

Purpose

The purpose of this paper is to explore primary care psychological therapists’ experiences of working with mid-life and older women presenting with intimate partner violence (IPV) and develop a theoretical framework using a grounded theory approach to identify the experiences of those practitioners working with this phenomenon.

Design/methodology/approach

Interviews with 17 practitioners were conducted. The data analysis was informed by a grounded theory approach, which requires three states of data coding: open, axial and selective. Data codes were thematically sorted into causal, contextual, strategic, intervening, interactional and consequential conditions.

Findings

A core state of therapist helplessness was uncovered. The framework demonstrates that psychological therapists can doubt their ability to work meaningfully with women over 45 years of age experiencing IPV. To avoid the core state of helplessness, therapists use strategies such as avoiding asking questions about partner violence, making assumptions of how patients interpret their own experiences, addressing symptoms rather than the root cause and going above and beyond in attempts to rescue patients. The consequence of therapists’ helplessness often results in burnout.

Research limitations/implications

The framework identifies barriers in working effectively with IPV and women in the mid-to older-aged populations.

Originality/value

This study is the first to suggest a framework that is grounded in practitioner experience with capability to transfer to a range of professionals working with mid-to older-aged women such as forensic, medical and specialist psychologists.