bluuebunny/crossref_metadata_2025 huggingface dataset:
Mass Screening for Celiac Disease Among School-aged Children: Toward Exploring Celiac Iceberg in Saudi Arabia
Authors: Al-Hussaini Abdulrahman , Troncone Riccardo , Khormi Musa , AlTuraiki Muath , Alkhamis Wahid , Alrajhi Mona , Halal Thana , Fagih Mosa , Alharbi Sahar , Bashir Muhammed Salman , Elchentoufi Aziz
Published: July 2017

Objectives:

We conducted this mass screening study to determine the prevalence of celiac disease (CD) and characterize the celiac iceberg among Saudi pediatric population in Riyadh, the capital city of Saudi Arabia.

Methods:

During the study period (January 2014–June 2016), we have conducted a cross-sectional, mass screening, immunoglobulin A-tissue transglutaminase (TTG-IgA)-based study on 7930 Saudi students from primary and intermediate schools in Riyadh. Students with positive TTG-IgA (>20 U/L) were called in the hospital to undergo a repeat of TTG-IgA; in those with borderline positive TTG-IgA (20–60 U/L), IgA-endomyseal antibody (EMA-IgA) test was performed. Children with TTG-IgA >60 U/L and children with borderline positive TTG-IgA and positive EMA-IgA were advised to undergo upper endoscopy and intestinal biopsies.

Results:

We identified 221 students with positive TTG-IgA (2.8%). CD was diagnosed in 119 cases (1.5%, 1:67 Saudi children) (mean age 11.5 ± 2.62 years; girls 81 [68%]). Another 51 children had persistently borderline positive TTG-IgA but negative EMA (0.64%) and the remaining 51 had transiently positive TTG-IgA. We have identified 3 clinical patterns in the screening-identified cases with CD: a silent form (37%), a mild symptomatic form characterized by gastrointestinal symptoms in presence of normal growth or overweight/obesity (48%), and gastrointestinal symptoms associated with impaired growth in 15%.

Conclusions:

Our study provided evidence of a high prevalence of CD among Saudi children (1.5%), a rate that is at least twice the average prevalence rate in Europe and North America.
Cesarean Section on the Risk of Celiac Disease in the Offspring
Authors: Koletzko Sibylle , Lee Hye‐Seung , Beyerlein Andreas , Aronsson Carin A. , Hummel Michael , Liu Edwin , Simell Ville , Kurppa Kalle , Lernmark Åke , Hagopian William , Rewers Marian , She Jin‐Xiong , Simell Olli , Toppari Jorma , Ziegler Anette‐G. , Krischer Jeffrey , Agardh Daniel ,   TEDDY Study Group
Published: July 2017

Objective:

Cesarean section (C‐section) is associated with various immune‐mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort.

Methods:

From 2004 to 2010, infants from the general population who tested positive for HLA DR3‐DQ2 or DR4‐DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive, they are retested after 3 to 6 months and those persistently positive defined as CDA. Associations of C‐section with maternal (age, education level, parity, pre‐pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon rank‐sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models.

Results:

Of 6087 analyzed singletons, 1600 (26%) were born by C‐section (Germany 38%, United States 37%, Finland 18%, Sweden 16%), and the remaining were born vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) developed CD. C‐section was associated with lower risk for CDA (hazard ratio [HR] = 0.85; 95% confidence interval [CI] 0.73, 0.99 P = 0.032) and CD (HR = 0.75; 95% CI 0.58, 0.98; P = 0.034). After adjusting for country, sex, HLA‐genotype, CD in family, maternal education, and breast‐feeding duration, significance was lost for CDA (HR = 0.91; 95% CI 0.78, 1.06; P = 0.20) and CD (HR = 0.85; 95% CI 0.65, 1.11; P = 0.24). Presurgical ruptured membranes had no influence on CDA or CD development.

Conclusion:

C‐section is not associated with increased risk for CDA or CD in the offspring.
Radiation Exposure and Attributable Cancer Risk in Patients With Esophageal Atresia
Authors: Yousef Yasmine , Baird Robert
Published: July 2017

Objectives:

Cases of esophageal carcinoma have been documented in survivors of esophageal atresia (EA). Children with EA undergo considerable amounts of diagnostic imaging and consequent radiation exposure potentially increasing their lifetime cancer mortality risk. This study evaluates the radiological procedures performed on patients with EA and estimates their cumulative radiation exposure and attributable lifetime cancer mortality risk.

Methods:

Medical records of patients with EA managed at a tertiary care center were reviewed for demographics, EA subtype, and number and type of radiological investigations. Existing normative data were used to estimate the cumulative radiation exposure and lifetime cancer risk per patient.

Results:

The present study included 53 patients with a mean follow‐up of 5.7 years. The overall median and maximum estimated effective radiation dose in the neonatal period was 5521.4 μSv/patient and 66638.6 μSv/patient, respectively. This correlates to a median and maximum estimated cumulative lifetime cancer mortality risk of 1:1530 and 1:130, respectively. Hence, radiation exposure in the neonatal period increased the cumulative cancer mortality risk a median of 130‐fold and a maximum of 1575‐fold in EA survivors.

Conclusions:

Children with EA are exposed to significant amounts of radiation and an increased estimated cumulative cancer mortality risk. Efforts should be made to eliminate superfluous imaging.
The Patient–Healthcare Professional Relationship and Communication in the Oncology Outpatient Setting
Authors: Prip Anne , Møller Kirsten Alling , Nielsen Dorte Lisbet , Jarden Mary , Olsen Marie-Helene , Danielsen Anne Kjaergaard
Published: July 2017

Background:

Today, cancer care and treatment primarily take place in an outpatient setting where encounters between patients and healthcare professionals are often brief.

Objective:

The aim of this study was to summarize the literature of adult patients’ experiences of and need for relationships and communication with healthcare professionals during chemotherapy in the oncology outpatient setting.

Methods:

The systematic literature review was carried out according to PRISMA guidelines and the PICO framework, and a systematic search was conducted in MEDLINE, CINAHL, The Cochrane Library, and Joanna Briggs Institute Evidence Based Practice Database.

Results:

Nine studies were included, qualitative (n = 5) and quantitative (n = 4). The studies identified that the relationship between patients and healthcare professionals was important for the patients’ ability to cope with cancer and has an impact on satisfaction of care, that hope and positivity are both a need and a strategy for patients with cancer and were facilitated by healthcare professionals, and that outpatient clinic visits framed and influenced communication and relationships.

Conclusions:

The relationship and communication between patients and healthcare professionals in the outpatient setting were important for the patients’ ability to cope with cancer.

Implications for Practice:

Healthcare professionals need to pay special attention to the relational aspects of communication in an outpatient clinic because encounters are often brief. More research is needed to investigate the type of interaction and intervention that would be the most effective in supporting adult patients’ coping during chemotherapy in an outpatient clinic.
Management of Scaphoid Fractures
Authors: Ko Jason H. , Pet Mitchell A. , Khouri Joseph S. , Hammert Warren C.
Published: July 2017

Learning Objectives:

After reading this article, the participant should be able to: 1. Understand the epidemiology, classification, and anatomy pertinent to the scaphoid. 2. Appropriately evaluate a patient with suspected scaphoid fracture, including appropriate imaging. 3. Understand the indications for operative treatment of scaphoid fractures, and be familiar with the various surgical approaches. 4. Describe the treatment options for scaphoid nonunion and avascular necrosis of the proximal pole.

The goal of this continuing medical education module is to present the preoperative assessment and the formation and execution of a surgical treatment plan for acute fractures of the scaphoid. In addition, secondary surgical options for treatment of scaphoid nonunion and avascular necrosis are discussed.
Extended Transconjunctival Lower Eyelid Blepharoplasty with Release of the Tear Trough Ligament and Fat Redistribution
Authors: Wong Chin-Ho , Mendelson Bryan
Published: July 2017

Background:

The transconjunctival lower eyelid blepharoplasty is advantageous for its quick recovery and low complication rates. Conventional techniques rely on fat removal to contour the lower eyelid. This article describes the authors’ extended transconjunctival lower eyelid blepharoplasty technique that takes dissection beyond the orbital rim to address aging changes on the midcheek.

Methods:

From December of 2012 to December of 2015, 54 patients underwent this procedure. Through a transconjunctival incision, the preseptal space was entered and excess orbital fat pads were excised. Medially, the origins of the palpebral part of the orbicularis oculi, the tear trough ligament, and orbital part of the orbicularis oculi were sequentially released, connecting the dissection with the premaxillary space. More laterally, the orbicularis retaining ligament was released, connecting the dissection with the prezygomatic space. Excised orbital fat was then grafted under the released tear trough ligament to correct the tear trough deformity. When the patients had significant maxillary retrusion, structural fat grafting was performed at the same time.

Results:

The mean follow-up was 10 months. High satisfaction was noted among the patients treated with this technique. The revision rate was 2 percent. Complication rates were low. No chemosis, prolonged swelling, lower eyelid retraction, or ectropion was seen in any patients.

Conclusion:

The extended transconjunctival lower blepharoplasty using the midcheek soft-tissue spaces is a safe and effective approach for treating patients presenting with eye bags and tear trough deformity.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Chemical Burns of the Eye
Authors: Ramponi Denise R.
Published: July 2017

Chemical burns of the eye are one of the most common eye injuries. The extent of the ocular surface damage is influenced by the type, temperature, volume, and pH of the corrosive substance and duration of exposure. Limbal ischemia found on eye assessment is the primary determinant of eventual visual outcome. Eye irrigation must be instituted immediately at the scene of exposure and continued in the emergency department to reduce visual impairment. Traditionally lactated Ringer's and normal saline have been used as irrigation fluids, although one systematic review demonstrates similar outcomes with other irrigation fluids. The Morgan Lens is a device that can be utilized to allow the provider to perform “hands free” eye irrigation. Complications of chemical burns are more common with alkali burns as these substances destroy the corneal epithelium and allow this corrosive base substance to penetrate deeper into the cornea.
Metatarsal Stress Fractures
Authors: Ramponi Denise R. , Hedderick Viki , Maloney Susan C.
Published: July 2017

Metatarsal stress fractures are also called “march fractures” or “marcher's foot.” They most commonly occur in the distal second and third metatarsals. The second and third metatarsals receive the majority of stress during ambulation and are less mobile compared with the other metatarsals. The predominant risk factor is excessive overuse with repetitive motions with little recovery time such as marching activities in the military. Any element that has a detrimental effect on bone density can predispose an individual to stress fractures. There is often a delay of 2 or more weeks from the onset of symptoms until visible fractures are able to be seen on radiographs. Initial treatment strategies involve rest, ice, nonweight bearing, and avoidance of exercise to prevent fracture displacement, nonunion, and other complications. Orthopedic referral will guide definitive care.
Assessment of clonal kinetics reveals multiple trajectories of dendritic cell development
Authors: Lin Dawn , Kan Andrey , Gao Jerry , Crampin Edmund , Hodgkin Philip D. , Naik Shalin H.
Published: July 2017

A thorough understanding of cellular development is incumbent on assessing the complexities of fate and kinetics of individual clones within a population. Here, we develop a system for robust periodical assessment of lineage outputs of thousands of transient clones and establishment ofbona fidecellular trajectories. We appraise the development of dendritic cells (DCs) from barcode-labeled hematopoietic stem and progenitor cells (HSPCs) by serially measuring barcode signatures, and visualize this multidimensional data using novel developmental interpolated t-distributed stochastic neighborhood embedding (Di-SNE) time-lapse movies. We identify multiple cellular trajectories of DC development that are characterized by distinct fate bias and expansion kinetics, and determine that these are intrinsically programmed. We demonstrate that conventional DC and plasmacytoid DC trajectories are largely separated already at the HSPC stage. This framework allows systematic evaluation of clonal dynamics and can be applied to other steady-state or perturbed developmental systems.
Maternal alcohol consumption during pregnancy and offspring epigenome-wide DNA methylation: findings from six general population-based birth cohorts
Authors: Sharp Gemma C , Arathimos Ryan , Reese Sarah E , Page Christian M , Felix Janine , Küpers Leanne K , Rifas-Shiman Sheryl L , Liu Chunyu ,   The Cohorts for Heart and Aging Research in Genomic Epidemiology plus (CHARGE +) methylation alcohol working group, Burrows Kimberley , Zhao Shanshan , Magnus Maria C , Duijts Liesbeth , Corpeleijn Eva , DeMeo Dawn L , Litonjua Augusto , Baccarelli Andrea , Hivert Marie-France , Oken Emily , Snieder Harold , Jaddoe Vincent , Nystad Wenche , London Stephanie J , Relton Caroline L , Zuccolo Luisa
Published: July 2017

Some evidence suggests that light-to-moderate alcohol consumption during pregnancy is associated with adverse outcomes in the offspring, but the precise biological mechanisms underlying such associations are currently unknown. Epigenetic modifications have been suggested as one potential explanation.

Within the Pregnancy and Childhood Epigenetics (PACE) consortium, we performed meta-analysis to combine information from six population-based birth cohort studies to investigate DNA methylation at over 450,000 sites in the cord blood of newborns differentially exposed to alcoholin utero. We were primarily interested in the effects of sustained consumption throughout pregnancy (data available for five cohorts, 3,075 mother-child pairs), which represents a prolonged prenatal exposure to alcohol, but we also explored binge-drinking and timing-specific exposures. In addition to looking for differential methylation at individual CpG sites, we also used two different methods, Comb-P and DMRcate, to identify differentially methylated regions (DMRs).

We found no strong evidence of association between any of our alcohol exposure measures and DNA methylation at any individual CpG site. Using Comb-P, we identified 19 DMRs in the offspring of mothers who drank throughout pregnancy compared to the offspring of mothers who gave up drinking at the start of pregnancy, but these were not validated using DMRcate.

In this multi-cohort study of the general population we found no evidence that maternal alcohol consumption during pregnancy is associated with offspring cord blood DNA methylation, which is in stark contrast to the multiple, strong associations that previous studies have found for maternal smoking. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure and a more global assessment of genomic DNA methylation might show evidence of association.
c-Myc Represses Transcription of the Epstein-Barr Virus Latent Membrane Protein 1 Early After Primary B Cell Infection
Authors: Price Alexander M. , Messinger Joshua E. , Luftig Micah A.
Published: July 2017

Recent evidence has shown that the EBV oncogene LMP1 is not expressed at high levels early after EBV-infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased fifty-fold between seven days post infection and the LCL state. Metabolic labeling of nascently transcribed mRNA indicated this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to early-infected B cells. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc expression both in LCLs and early after primary B-cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B-cell infection directly represses LMP1 transcription.

IMPORTANCE

EBV is a highly successful pathogen that latently infects greater than 90% of adults worldwide and is also causally associated with a number of B-cell malignancies. EBV expresses a set of viral oncoproteins and non-coding RNAs during the latent life cycle with the potential to promote cancer. Critical among these is the viral latent membrane protein, LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here, we show that the transcription of LMP1 can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV-encoded oncogenes will allow us to better treat cancers that rely on these viral products for survival.
Acute stress induces long-lasting alterations in the dopaminergic system of female mice
Authors: Wichmann Romy , Vander Weele Caitlin M. , Yosafat Ariella S. , Schut Evelien H.S. , Verharen Jeroen P. H. , Sridharma Suganya , Siciliano Cody A. , Izadmehr Ehsan M. , Farris Kathryn M. , Wildes Craig P. , Kimchi Eyal Y. , Tye Kay M.
Published: July 2017

Stress is a risk factor for many neuropsychiatric disorders, and the mesolimbic dopamine (DA) pathway is a crucial node of vulnerability. Despite the high prevalence of stress-related neuropsychiatric disorders in women, preclinical knowledge on the impact of stress on neural circuitry has predominantly been acquired in males. Here, we examine how a non-social stressor impacts the effect of DA neurotransmission on social and reward-related behaviors in female mice. Acute stress exposure attenuated the anti-social effects of photoinhibiting ventral tegmental area (VTA) DA neurons and transformed photoactivation of these cells into an anti-social signal. Fast-scan cyclic voltammetry (FSCV) revealed an enhancement in optogenetically-induced DA release after stress. 60 days after stress, mice showed distinct patterns of intra-cranial self-stimulation of VTA DA neurons. Our results reveal the impact stress exerts on females and show that neural and behavioral changes induced by acute stress exposure are still present months later.
Experimental evolution and genome data analysis ofCandida albicansreveals cryptic bacteria in single yeast colonies
Authors: Carmo Ferreira Bruno Danielle do , Fernanda Bartelli Thais , Ronqui Rodrigues Camila , Briones Marcelo R. S.
Published: July 2017

At least 25% of patients with positiveCandida albicansbloodstream infection also have one or more bacterial species associated with the infection. These polymicrobial infections are usually caused by coagulase-negative staphylococci, most commonlyStaphylococcus epidermidisand are associated with significantly worse clinical outcomes as compared to monomicrobial infections. Here we show bacteria are present inC. albicanscultures started from isolated single colony platting. These co-evolving bacteria can only be detected by the use of specific selective medium and/or long periods of incubation from 8 days up to 48 weeks (approximately 4,000 generations), used in experimental evolution methods. The detection of these co-evolving bacteria is highly dependent on the type of enzyme used for 16S rRNA gene amplification and is often missed in clinical laboratory analysis because of short incubation periods, media and temperatures, used in mycology clinical routine, that are unfavorable for bacterial growth. In this study, we identified bacteria in cultures of differentC. albicansisolates from long term, continuous growth by molecular analysis and microscopy. Also, we confirmed the presence of these co-evolving bacteria by identification ofS. epidermidisgenome segments in sequencing reads of theC. albicansreference strain SC5314 genome sequencing project raw data deposited in GenBank. This result rules out the possibility of laboratory specific contamination. Also, we show that the presence of associated bacteria correlates with antifungal resistance alterations observed in growth under hypoxia. Our findings show the intense interaction betweenC. albicansyeasts and bacteria and have direct implications in yeast clinical procedures, especially concerning patient treatment.
Anin vivobinding assay for RNA-binding proteins based on repression of a reporter gene
Authors: Katz Noa , Cohen Roni , Solomon Oz , Kaufmann Beate , Eden Noa , Atar Orna , Yakhini Zohar , Goldberg Sarah , Amit Roee
Published: July 2017

We employ a reporter assay and Selective 2′-hydroxyl acylation analysed by primer extension sequencing (SHAPE-seq) to study translational regulation by RNA-binding proteins, in bacteria. We designed 82 constructs, each with a single hairpin based on the binding sites of the RNA-binding coat proteins of phages MS2, PP7, GA, and Qβ, at various positions within the N-terminus of a reporter gene. In the absence of RNA-binding proteins, the translation level depends on hairpin location, and exhibits a three-nucleotide periodicity. For hairpin positions within the initiation region, we observe strong translational repression in the presence of its cognate RNA-binding protein.In vivo SHAPE-seqresults for a representative construct indicate that the repression phenomenon correlates with a wide-swath of protection, including the hairpin and extending past the ribosome binding site. Consequently, our data suggest that the protection provided by the RBP-hairpin complex inhibits ribosomal initiation. Finally, utilizing the repression phenomenon for quantifying protein-RNA binding affinityin vivo, we both observe partially contrasting results to previousin vitroandin situstudies, and additionally, show that this method can be used in a high-throughput assay for a quantitative study of protein-RNA bindingin vivo.
Facilitation of motor excitability during listening to spoken sentences is not modulated by noise or semantic coherence
Authors: Panouillères Muriel T.N. , Boyles Rowan , Chesters Jennifer , Watkins Kate E. , Möttönen Riikka
Published: July 2017

Comprehending speech can be particularly challenging in a noisy environment and in the absence of semantic context. It has been proposed that the articulatory motor system would be recruited especially in difficult listening conditions. However, it remains unknown how signal-to-noise ratio (SNR) and semantic context affect the recruitment of the articulatory motor system when listening to continuous speech. The aim of the present study was to address the hypothesis that involvement of the articulatory motor cortex increases when the intelligibility and clarity of the spoken sentences decreases, because of noise and the lack of semantic context. We applied Transcranial Magnetic Stimulation (TMS) to the lip and hand representations in the primary motor cortex and measured motor evoked potentials from the lip and hand muscles, respectively, to evaluate motor excitability when young adults listened to sentences. In Experiment 1, we found that the excitability of the lip motor cortex was facilitated during listening to both semantically anomalous and coherent sentences in noise, but neither SNR nor semantic context modulated the facilitation. In Experiment 2, we replicated these findings and found no difference in the excitability of the lip motor cortex between sentences in noise and clear sentences without noise. Thus, our results show that the articulatory motor cortex is involved in speech processing even in optimal and ecologically valid listening conditions and that its involvement is not modulated by the intelligibility and clarity of speech.
A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging
Authors: Zeighami Yashar , Fereshtehnejad Seyed-Mohammad , Dadar Mahsa , Collins D. Louis , Postuma Ronald B. , Mišić Bratislav , Dagher Alain
Published: July 2017

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even inde novopatients.
Multiplexed nanopore sequencing of HLA-B locus in Māori and Polynesian samples
Authors: Ton K.N.T. , Cree S.L. , Gronert-Sum S.J. , Merriman T.R. , Stamp L.K. , Kennedy M.A
Published: July 2017

The human leukocyte antigen (HLA) system is a gene family that encodes the human major histocompatibility complex (MHC). HLA-B is the most polymorphic gene in the MHC class I region, comprised of 4,765 HLA-B alleles (IPD-IMGT/HLA Database Release 3.28). Many HLA-B alleles have been associated with adverse drug reactions and disease risks, and we are interested in developing efficient methods for analysis of HLA alleles in this context. Here we describe an approach to HLA-B typing using multiplexed next generation sequencing on the MinION™ nanopore sequencer (Oxford Nanopore Technologies), combined with data analysis with the SeqNext-HLA software package (JSI Medical Systems GmbH, Ettenheim, Germany). The nanopore sequencer offers the advantages of long-read capability and single molecule reads, which can facilitate effective haplotyping. We developed this method using reference samples of known HLA-B type as well as individuals of New Zealand Māori or Pacific Island (Polynesian) descent, because HLA-B diversity in these populations is not well understood. We demonstrate here that nanopore sequencing of barcoded, pooled, 943 bp polymerase chain reaction (PCR) amplicons of 49 DNA samples, on one R9.4 flowcell (Oxford Nanopore Technologies), generated ample read depth for all samples. Sequence analysis using SeqNext-HLA software assigned HLA-B alleles to all samples at high-resolution with very little ambiguity. Our PCR-based next generation sequencing method is a scaleable and efficient approach for genotyping HLA-B and potentially any other HLA locus. Finally, we report our findings on HLA-B genotypes of this cohort, which adds to our understanding of HLA-B allele frequencies among Māori and Polynesian people.
INO80 Chromatin Remodelling Coordinates Metabolic Homeostasis with Cell Division
Authors: Gowans Graeme J. , Schep Alicia N. , Wong Ka Man , King Devin A. , Greenleaf William J. , Morrison Ashby J.
Published: July 2017

Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of allS.cerevisiaegenes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the Yeast Metabolic Cycle (YMC). Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here we demonstrate that the INO80 chromatin-remodelling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin in order to restrict proliferation to metabolically optimal states.
Designing an intuitive web application for drug discovery scientists
Authors: Karamanis Nikiforos , Carvalho-Silva Denise , Cham Jennifer A. , Fumis Luca , Hasan Samiul , Hulcoop David , Koscielny Gautier , Maguire Michael , Newell William , Ong ChuangKee , Papa Eliseo , Pierleoni Andrea , Pignatelli Miguel , Pundir Sangya , Rowland Francis , Vamathevan Jessica , Watkins Xavier , Barrett Jeffrey C. , Dunham Ian
Published: July 2017

Although a scientific web application that is intuitive can help scientists utilize data more easily and advance their research, there is little guidance on how to design such an application in the academic literature. We discuss how we designed an intuitive application for bench scientists working in drug discovery following an approach that can be applied to the design and development of scientific resources in a broad range of disciplines.
Comparison of decision-related signals in sensory and motor preparatory responses of neurons in Area LIP
Authors: Shushruth S. , Mazurek Mark , Shadlen Michael N.
Published: July 2017

Neurons in the lateral intraparietal area (LIP) of Macaques exhibit both sensory and oculomotor preparatory responses. During perceptual decision making, the preparatory responses have been shown to track the state of the evolving evidence leading to the decision. The sensory responses are known to reflect categorical properties of visual stimuli, but it is not known if these responses also track evolving evidence. We compared sensory and oculomotor-preparatory responses in the same neurons during a direction discrimination task when either the discriminandum (random dot motion) or an eye movement choice-target was in the neuron’s response field. Both configurations elicited task related activity, but only the motor preparatory responses reflected evidence accumulation. The results are consistent with the proposal that evolving decision processes are supported by persistent neural activity in the service of actions or intentions, as opposed to high order representations of stimulus properties.

SIGNIFICANCE STATEMENT

Perceptual decision making is the process of choosing an appropriate motor action based on perceived sensory information. Association areas of the cortex play an important role in this sensory-motor transformation. The neurons in these areas show both sensory- and motor-related activity. We show here that, in the macaque parietal association area LIP, signatures of the process of evidence accumulation that underlies the decisions are predominantly reflected in the motor-related activity. This finding supports the proposal that perceptual decision making is implemented in the brain as a process of choosing between available motor actions rather than as a process of representing the properties of the sensory stimulus.
Synthesis and crystal structures of [Ph3PCH2PPh3]I2 dichloromethane disolvate and [Ph3PCH2PPh3](BI4)2
Authors: Ganguly Rakesh , Jevtovic Violeta
Published: July 2017

Reaction of BI3 with carbodiphosphorane, C(PPh3)2, gives a mixture of the dicationic compounds, methylenebis(triphenylphosphonium) diiodide dichloromethane disolvate, C37H32P2
2+·2I−·2CH2Cl2 or [Ph3PCH2PPh3]I2·2CH2Cl2 (I), methylenebis(triphenylphosphonium) bis(tetraiodoborate), C37H32P2
2+·2BI4
− or [Ph3PCH2PPh3](BI4)2 (II). Solvents are the source of the protons at the ylidic C atom. The P—C—P angle is 124.1 (2)° for (I) and 121.7 (3)° for (II), while the two P—C bond lengths are 1.804 (4) and 1.807 (5) Å in (I), and 1.817 (5) and 1.829 (5) Å in (II). In the crystal of (I), the protons of the central P—CH2—P C atom exhibit weak C—H...I hydrogen bonds with the respective anions. The anions in turn are linked to the dichloromethane solvent molecules by C—H...I hydrogen bonds. In the crystal of (II), one of the BI4
− anions is linked to a phenyl H atom via a weak C—H...I hydrogen bond.
N-[4-(4-Fluorophenyl)-1,3-thiazol-2-yl]-3-(4-methoxyphenyl)-4-methylbenzamide
Authors: Archana K. , Lakshmithendral K. , Saravanan K. , Kabilan S. , Selvanayagam S.
Published: July 2017

In the title compound, C24H19FN2O2S, the dihedral angle between the fluorophenyl and thiazole rings is 12.8 (1)°. In the crystal, molecules are linked via strong N—H...O hydrogen bonds, forming C(11) chains propagating along [001]. In addition, C—H...O interactions are observed in this structure, forming C(10) chains propagating along [001].
A revisit to stock market contagion and portfolio hedging strategies
Authors: Singh Amanjot , Singh Manjit
Published: July 2017

Purpose

This paper aims to attempt to re-capture the stock market contagion effect from the US to the BRIC equity markets during the recent global financial crisis in a multivariate framework. Apart from this, the study also identifies optimal portfolio hedging strategies to minimize the underlying portfolio risk during the period undertaken for the purpose of study.

Design/methodology/approach

To account for the dynamic interactions, the study uses vector autoregression (p) dynamic conditional correlation (DCC)-asymmetric generalized autoregressive conditional heteroskedastic (1,1) model in a multivariate framework, coupled with a monthly heat map relating to the co-movement between the US and the BRIC equity markets during the period 2007-2009. Finally, by following the studies, Hammoudeh et al. (2010) and Syriopoulos et al. (2015), the time-varying optimal portfolio hedge ratios and weights are computed.

Findings

The results report a contagion impact of the US subprime crisis (following the collapse of the Lehman Brothers) on the Indian and Russian stock markets only. On the other hand, a higher degree of interdependence between the US and Brazilian market has been observed. The US and Chinese equity markets indicate a relatively lower level of interdependence among themselves. The optimal hedge ratios are found to be most effective for a portfolio comprising the US and Chinese stocks even during the crisis period. A US investor should invest approximately 30 cents in the Indian market and rest of the 70 cents in the US market in a US$1 portfolio to minimize the portfolio risk without lowering the expected returns. During the crisis period (2007-2009), the optimal portfolio weights indicate a higher weightage to the BRIC stocks.

Practical implications

The results support the construction of optimal US–BRIC stock portfolios and provide an insight to the investors and policy makers both domestic as well as international, with regard to the contagion impact and interdependence, especially during a crisis period.

Originality/value

The study uses a DCC model in a multivariate framework instead of bivariate, wherein all the markets are factored into a single interaction framework across a very long period (2004-2014). Second, a heat map of monthly correlation combinations has been created for the period 2007-2009, to comprehend the contagion impact or interdependence among the markets. Finally, the study ascertains time-varying optimal hedge ratios and portfolio weights for a two asset portfolio, from a US investor viewpoint, making the study first of its kind in all the perspectives.
Legal source, institutional quality and FDI flows in Africa
Authors: Bokpin Godfred A. , Mensah Lord , Asamoah Michael E.
Published: July 2017

Purpose

This paper aims to find out how the legal system interacts with other institutions in attracting Foreign Direct Investment (FDI) into Africa.

Design/methodology/approach

The authors use annual panel data of 49 African countries over the period 1980 to 2011, and use the system generalized method of moments (GMM) estimation technique and pooled panel data regression.

Findings

The authors find that the source of a country’s legal system deters FDI inflow as institutions alone cannot bring in the needed quantum of FDI. In terms of trading blocs, it was found that there is negative significant relationship between institutional quality and FDI for South African Development Community (SADC) as well as Economic Community of West Africa States (ECOWAS) countries.

Practical implications

For policy implications, the results suggest that reliance on institutions alone cannot project the continent to attract the needed FDI.

Originality/value

Empiricists have devoted considerable effort to estimating the relationship between institutions and FDI on the African continent, but this paper seeks to ascertain the effect of legal systems and institutional quality within African specific trade and regional blocks.
Management challenges in British Columbia’s healthcare system
Authors: Greenwald Howard Peter
Published: July 2017

Purpose

The purpose of this paper is to identify the operational and management challenges in a globally budgeted, regionalized healthcare system and their implications for public service.

Design/methodology/approach

Concentrating on British Columbia’s regional health authorities (RHAs) and hospitals, this study utilized data from interviews of key informants, documents (histories, legislation, agreements between RHAs and provincial government, and RHA organizational charts), news reports, and participant observation at board meetings.

Findings

Challenges encountered by the managers include accommodating powerful stakeholders (elected officials, providers, and organized publics), adhering to fixed budgets, obtaining capital from public sources, and adjusting to government turnover. In response, the managers engage in balancing priorities of stakeholders, shifting of resources within and across sites and operating units, and working strategically with the capital allocation process. Responses of managers to these challenges have promoted stability but raise concerns about attaining the system’s goals.

Practical implications

Management challenges and potential patterns of response should be considered in assessing the options for health system reforms. Many countries periodically reorganize their healthcare systems, and recognition of potential management challenges can contribute to the achievement of objectives sought in these reforms.

Originality/value

Although studies have demonstrated that management affects the implementation of public programs in several areas, little research has focused on the relationships between features of health systems, management responses, and potential outcomes.
A4A relationships
Authors: Polese Francesco , Pels Jaqueline , Tronvoll Bård , Bruni Roberto , Carrubbo Luca
Published: July 2017

Purpose

The purpose of this paper is to investigate the characteristics of actors that allow them to relate to others actors in the system through shared intentionality (orientation) and the nature of the A4A relationship and the results that such interactions bring to the emergent system based on this shared purpose (finality).

Design/methodology/approach

The topic is approached by theoretical analysis and conceptual development of three integrative frameworks: the sociological perspective, service-dominant logic and a particular perspective of system thinking: the viable system approach (vSa).

Findings

The A4A relationships involve value co-creation based on actors integrating their resources and acting with intentionality to obtain value by providing benefits to other parties and by belonging to the emergent viable system; actor acts for other actors directly involved in the relationship generating positive effects for the whole system in which it is contextualized.

Research limitations/implications

Future empirical research might better support findings.

Social implications

Many social implications deriving from an augmented role of actors engaged within social relationships in co-creation exchanges. From the title of the paper A4A over on the manuscript describes numerous social inferences of actors in co-creation.

Originality/value

A4A is a relationship formed by actors that interact for the benefit of the whole system in which are involved. They find own benefit from the benefit created for the system in which they live and act. In A4A relationships the value of the single actor comes from the participation to the viability of the whole system.
The viable decision maker for CAS survival: how to change and adapt through fitting process
Authors: Carrubbo Luca , Iandolo Francesca , Pitardi Valentina , Calabrese Mario
Published: July 2017

Purpose

The purpose of this paper is to investigate the decision-making process in the management of the complex adaptive systems (CAS), particularly focusing on the dimensions that affect the individual decision maker (DM) when passing from decision to behavior in fitting processes. Although the importance of the general process of fitting in terms of organizational design has been highlighted in earlier studies, a closer focus on the DM perspective is required.

Design/methodology/approach

Starting from the theoretical frameworks of viable systems approach (vSa) and addressing the evolving concepts of change and adaptation in CAS, the work takes the DM perspective and investigates the dimensions involved in the paths that lead complex decisions into behaviors, when referring to fitting processes. The paper reviews the vSa and the concept of CAS, deepening the decision making in fitting processes. Then, the paper proceeds to discuss the schemes and the categories that affect, at different levels, the decision and behavioral choices by proposing an interpretative framework.

Findings

The paper proposes a general framework useful to recognize/identify which are the elements/dimensions that have to be considered when organizations change in pursuing survival. The findings of the paper also show how adopting a vSa as a meta-model can be insightful to the understanding of service systems and useful in fully comprehending decision-making processes and behavior in complex adaptive system.

Originality/value

The originality of this paper lies in exploring the decision making process in CAS, adopting a closer perspective on the single DM through the lens of the vSa.
Measuring customer value co-creation behavior
Authors: Tommasetti Aurelio , Troisi Orlando , Vesci Massimiliano
Published: July 2017

Purpose

In line with the precepts of service-dominant logic (SDL), the purpose of this paper is to devise a measurement framework of customer value co-creation practices during the service process.

Design/methodology/approach

Answering the call of McColl-Kennedy et al. (2012), the present study develops a general conceptual model for the measurement of customer value co-creation behavior, in line with the procedure elaborated by Churchill (1979). In particular, the paper focuses on the first stage of the protocol, corresponding to the specification of the domain of the construct.

Findings

The study shows that the scale for measuring behavioral processes in customer value co-creation has an implicit hierarchical structure based on eight activities to ensure adequate semantic coverage of the concept: cerebral activities, cooperation, information research and collation, the combination of complementary activities, changes in habits, co-production, co-learning, and connection. Moreover, the work highlights that the analysis of customer value co-creation behavior leads to three diverse steps of value co-creation and various levels of interaction.

Originality/value

By systematizing the construct of customer value co-creation behavior within a comprehensive framework, the conceptual model attempts to fill a gap evidenced by previous research in order to show that actions performed by users during the value co-creation process strictly conform to SDL assumptions. Moreover, the framework underpinning the practical application of SDL principles could benefit future practitioners and suggest interesting implications for future research.