bluuebunny/crossref_metadata_2025 huggingface dataset:
Very-high-cycle fatigue crack initiation and propagation behaviours of magnesium alloy ZK60
Authors: He Chao , Liu Yongjie , Li Jiukai , Yang Kun , Wang Qingyuan , Chen Qiang
Published: December 2017

The aim of this paper is to assess the very-high-cycle fatigue (VHCF) behaviour of a magnesium alloy (ZK60). Results indicate that the fatigue crack initiates from an area consisting of many distributed facets, while the region of early crack propagation is characterised by parallel traces, based on a fractographic analysis. The significant differences in morphology around the crack initiation area result from the interaction between the deformation twinning and the plastic zone at the crack tip. In addition, the fatigue crack propagation rate around the crack initiation site is also estimated based on a modified Murakami model. It is found that the formation stage for the fatigue crack is of great importance to the fatigue failure mechanism in the VHCF regime.
Effect of Si on the partitioning of Mn between cementite and ferrite
Authors: Tu Yiyou , Huang Linghui , Zhang Qi , Zhou Xuefeng , Jiang Jianqing
Published: December 2017

The interlamellar spacings of pearlitic steels gradually increase as the isothermal transformation temperatures, correspondingly, the tensile strengths decrease, satisfying the Hall–Petch relationship. Si virtually completes its partitioning process during the eutectoid transformation. A depletion of Mn and an accumulation of Si are found in the concentration profiles of 0.95%-Si steel transformed at 793 K in the ferrite, but not in 0.22%-Si steel. It may attribute them to the Si–Mn diffusional flux couplings, which due to the strong interaction between Si and Mn atoms in the α-Fe. Transformation temperature increases to 873 K, a large amount of Mn atoms coming from ferrite cannot timely diffusion to cementite lamella core, forming a localised retention of Mn in the cementite phase side nearby the interface.

This is part of a thematic issue on Pearlitic Steel Wires.
Curcumin and its derivatives inhibit 2,3,7,8,-tetrachloro-dibenzo-p-dioxin-induced expression of drug metabolizing enzymes through aryl hydrocarbon receptor-mediated pathway
Authors: Nakai Rika , Fukuda Shun , Kawase Masaya , Yamashita Yoko , Ashida Hitoshi
Published: December 2017

Certain dioxins, including 2,3,7,8,-tetrachloro-dibenzo-p-dioxin (TCDD), are exogenous ligands for an aryl hydrocarbon receptor (AhR) and induces various drug-metabolizing enzymes. In this study, we examined the effect of curcumin on expression of drug-metabolizing enzymes through the AhR and NF-E2 related factor 2 (Nrf2) pathways. Curcumin dose-dependently inhibited TCDD-induced expression of phase I enzyme cytochrome P450 1A1 (CYP1A1) and phase II enzymes NAD(P)H:quinone oxidoreductase-1 (NQO1) and heme oxygenase 1 (HO-1) but not tert-butyl hydroquinone-induced NQO1 and HO-1, suggesting that curcumin inhibited only AhR pathway, but not Nrf2 one directly. Furthermore, we used 14 curcumin derivatives and obtained the correlation between hydrophobicity of the compounds and suppressive effect against AhR transformation. Results from the quantitative structure active correlative analysis indicated that methoxy groups and β-diketone structure possessing keto-enol tautomerism in curcumin were necessary to inhibit AhR transformation, and the addition of methyl and methoxy group(s) to the curcumin increased the inhibition effect.
Testing of Two Selective Flatfish Sorting-Grid Bycatch Reduction Devices in the U.S. West Coast Groundfish Bottom Trawl Fishery
Authors: Lomeli Mark J. M. , Wakefield W. Waldo , Herrmann Bent
Published: December 2017

In the U.S. West Coast limited-entry (LE) groundfish bottom trawl fishery, catches of stocks with restrictive harvest limits (e.g., Darkblotched Rockfish Sebastes crameri, Sablefish Anoplopoma fimbria, and Pacific Halibut Hippoglossus stenolepis) continue to hinder many fishermen's ability to fully utilize their quota shares of more abundant flatfish stocks (e.g., Dover Sole Microstomus pacificus and Petrale Sole Eopsetta jordani). We used a recapture net to examine the size-selection characteristics of two selective flatfish sorting-grid bycatch reduction devices (BRDs), which were designed to reduce catches of Pacific Halibut and non-flatfish species while retaining target flatfishes. The two devices were identical in materials and design except that the sorting-grid dimensions differed (BRD-1: 6.4- × 25.4-cm grid size; BRD-2: 6.4- × 30.5-cm grid size). The size selectivity for rockfishes, other roundfishes, Pacific Halibut, English Sole Parophrys vetulus, and Rex Sole Glyptocephalus zachirus did not differ significantly between the two designs. However, for 53–58-cm TL Arrowtooth Flounder Atheresthes stomias, 39–53-cm TL Dover Sole, and 36–49-cm TL Petrale Sole, BRD-1 retained significantly higher proportions of these length-classes than did BRD-2. Combined, the mean flatfish retention by weight (not including Pacific Halibut) was 89.3% (95% confidence interval [CI] = 87.1–91.5%) for BRD-1 and 81.7% (95% CI = 80.0–83.4%) for BRD-2. Compared to previous flatfish sorting-grid selectivity work conducted in the LE bottom trawl fishery, BRD-1 showed the ability to improve the overall retention of flatfishes while reducing catches of nontarget and constraining species.
Microglia in Alzheimer’s disease
Authors: Hansen David V. , Hanson Jesse E. , Sheng Morgan
Published: December 2017

Proliferation and activation of microglia in the brain, concentrated around amyloid plaques, is a prominent feature of Alzheimer’s disease (AD). Human genetics data point to a key role for microglia in the pathogenesis of AD. The majority of risk genes for AD are highly expressed (and many are selectively expressed) by microglia in the brain. There is mounting evidence that microglia protect against the incidence of AD, as impaired microglial activities and altered microglial responses to β-amyloid are associated with increased AD risk. On the other hand, there is also abundant evidence that activated microglia can be harmful to neurons. Microglia can mediate synapse loss by engulfment of synapses, likely via a complement-dependent mechanism; they can also exacerbate tau pathology and secrete inflammatory factors that can injure neurons directly or via activation of neurotoxic astrocytes. Gene expression profiles indicate multiple states of microglial activation in neurodegenerative disease settings, which might explain the disparate roles of microglia in the development and progression of AD pathology.
FcRn is mother’s milk to allergen tolerance
Authors: Lambrecht Bart N.
Published: December 2017

In this issue Ohsaki et al. (https://doi.org/10.1084/jem.20171163) explain how breastfeeding can prevent the onset of food allergies in offspring by instructing T reg formation via neonatal Fc receptor (FcRn)–mediated transfer and uptake of allergen-containing IgG immune complexes (Ig-ICs) by gut dendritic cells (DCs).
Integrative model of coronary flow in anatomically based vasculature under myogenic, shear, and metabolic regulation
Authors: Namani Ravi , Kassab Ghassan S. , Lanir Yoram
Published: December 2017

Coronary blood flow is regulated to match the oxygen demand of myocytes in the heart wall. Flow regulation is essential to meet the wide range of cardiac workload. The blood flows through a complex coronary vasculature of elastic vessels having nonlinear wall properties, under transmural heterogeneous myocardial extravascular loading. To date, there is no fully integrative flow analysis that incorporates global and local passive and flow control determinants. Here, we provide an integrative model of coronary flow regulation that considers the realistic asymmetric morphology of the coronary network, the dynamic myocardial loading on the vessels embedded in it, and the combined effects of local myogenic effect, local shear regulation, and conducted metabolic control driven by venous O2 saturation level. The model predicts autoregulation (approximately constant flow over a wide range of coronary perfusion pressures), reduced heterogeneity of regulated flow, and presence of flow reserve, in agreement with experimental observations. Furthermore, the model shows that the metabolic and myogenic regulations play a primary role, whereas shear has a secondary one. Regulation was found to have a significant effect on the flow except under extreme (high and low) inlet pressures and metabolic demand. Novel outcomes of the model are that cyclic myocardial loading on coronary vessels enhances the coronary flow reserve except under low inlet perfusion pressure, increases the pressure range of effective autoregulation, and reduces the network flow in the absence of metabolic regulation. Collectively, these findings demonstrate the utility of the present biophysical model, which can be used to unravel the underlying mechanisms of coronary physiopathology.
ASAR: visual analysis of metagenomes in R
Authors: Orakov Askarbek N , Sakenova Nazgul K , Sorokin Anatoly , Goryanin Igor I
Published: December 2017

Motivation

Functional and taxonomic analyses are critical steps in understanding interspecific interactions within microbial communities. Currently, such analyses are run separately, which complicates interpretation of results. Here we present the ASAR interactive tool for simultaneous analysis of metagenomic data in three dimensions: taxonomy, function, metagenome.

Results

An interactive data analysis tool for selection, aggregation and visualization of metagenomic data is presented. Functional analysis with a SEED hierarchy and pathway diagram based on KEGG orthology based upon MG-RAST annotation results is available.

Availability and implementation

Source code of the ASAR is accessible at GitHub (https://github.com/Askarbek-orakov/ASAR).
Integrating 5hmC and gene expression data to infer regulatory mechanisms
Authors: Mitrea Cristina , Wijesinghe Priyanga , Dyson Greg , Kruger Adéle , Ruden Douglas M , Drăghici Sorin , Bollig-Fischer Aliccia
Published: December 2017

Motivation

Epigenetic mechanisms are known to play a major role in breast cancer. However, the role of 5-hydroxymethylcytosine (5hmC) remains understudied. We hypothesize that 5hmC mediates redox regulation of gene expression in an aggressive subtype known as triple negative breast cancer (TNBC). To address this, our objective was to highlight genes that may be the target of this process by identifying redox-regulated, antioxidant-sensitive, gene-localized 5hmC changes associated with mRNA changes in TNBC cells.

Results

We proceeded to develop an approach to integrate novel Pvu-sequencing and RNA-sequencing data. The result of our approach to merge genome-wide, high-throughput TNBC cell line datasets to identify significant, concordant 5hmC and mRNA changes in response to antioxidant treatment produced a gene set with relevance to cancer stem cell function. Moreover, we have established a method that will be useful for continued research of 5hmC in TNBC cells and tissue samples.

Availability and implementation

Data are available at Gene Expression Omnibus (GEO) under accession number GSE103850.
Massive stars in the Sagittarius Dwarf Irregular Galaxy
Authors: Garcia Miriam
Published: December 2017

Low metallicity massive stars hold the key to interpret numerous processes in the past Universe including re–ionization, starburst galaxies, high-redshift supernovae, and γ-ray bursts. The Sagittarius Dwarf Irregular Galaxy [SagDIG, 12+log(O/H) = 7.37] represents an important landmark in the quest for analogues accessible with 10-m class telescopes. This Letter presents low-resolution spectroscopy executed with the Gran Telescopio Canarias that confirms that SagDIG hosts massive stars. The observations unveiled three OBA-type stars and one red supergiant candidate. Pending confirmation from high-resolution follow-up studies, these could be the most metal-poor massive stars of the Local Group.
Predictability of Supine Radiographs for Determining In-Brace Correction for Adolescent Idiopathic Scoliosis
Authors: Cheung Jason Pui Yin , Yiu Karen Kar Lum , Vidyadhara Srinivasa , Chan Peggy Pui Yee , Cheung Prudence Wing Hang , Mak Kin Cheung
Published: December 2017

Study Design.

Retrospective radiographic study.

Objective.

To assess whether flexibility as revealed by the supine radiograph, predicts in-brace curve correction.

Summary of Background Data.

Currently there is no consensus regarding a standard method to assess curve flexibility and immediate brace effectiveness in treating adolescent idiopathic scoliosis (AIS). Brace fabrication methods may be variable but ideally it should achieve maximal curve correction. Curve flexibility governs the degree of curve correction in-brace and hence dynamic radiographs are commonly performed prior to brace fitting.

Methods.

This was a radiographic analysis of AIS patients treated with underarm bracing. Correlation of pre-brace, supine, and immediate in-brace Cobb angles was performed. Relationship with possible contributing factors including age, sex, body height, weight, age at menarche and Risser staging was studied. Major and minor curves were compared independently for correlation but the regression model was constructed based on the major curve only.

Results.

From 105 patients with mean age of 12.2 ± 1.2 years at brace fitting, supine Cobb angle measurement has significant correlation with immediate in-brace Cobb angle (r = 0.740). Univariate analyses showed no significant relationship with age, weight, height, date of menarche, Risser stage or pre-brace Cobb angle. Our regression model (in-brace Cobb angle = 0.809 × supine Cobb angle) had good fit of the data.

Conclusion.

Supine radiograph predictably determines the flexibility of the scoliotic curve to brace treatment. It can be used as a guideline to determine the amount of correction achievable with brace-wear. The effectiveness of the brace is dependent on the inherent flexibility of the curve rather than its size or type.

Level of Evidence: 3
Anatomical Study of a Novel Iliosacral Screw Placement for Sacrum-Pelvis in Adult Via Computed Tomography Reconstruction
Authors: Sun Xu , Li Song , Qiu Yong , Chen Zhonghui , Chen Xi , Xu Liang , Zhu Zezhang
Published: December 2017

Study Design.

This is a cross-sectional study.

Objective.

To investigate the feasibility and safety of a novel iliosacral screw placement for sacrum-pelvis in adult pelvis by computed tomography (CT) reconstruction.

Summary of Background Data.

The optimal technique of spino-pelvic fixation is still being developed and redefined. However, neither the relevant anatomic parameters nor the potential spinal canal involvement for a novel iliosacral screw placement have been clearly analyzed.

Methods.

A total of 60 adults with normal pelvis, with the age ranging from 24 to 79 years old, were included in this study. Based on three-dimensional (3D) CT reconstruction of each pelvis, virtual iliosacral screw channel was identified bilaterally, the trajectory of which was characterized with the optimal width and length from the ilium to the sacrum. The virtual iliosacral screw channel that holding the greatest width and length of osseous channel was measured by rotating the 3D pelvis. Measurements of the determined channel on either side included iliosacral-screw-related and connector-related parameters.

Results.

There was a virtual iliosacral screw channel passing through the ilium, the iliosacral joint and then into the sacrum on either side of each pelvis. The caudal angle, convergent angle, and maximal length were 16.3 ± 3.0°, 61.3 ± 5.9°, 97.0 ± 5.6 mm in male, respectively. In female, they were 16.4 ± 3.9°, 63.0 ± 5.5° and 96.2 ± 6.0 mm, respectively. The ideal direction of the connector was from posteromedial to anterolateral. The cephalad angle, divergent angle, and embedding depth of the connector were 28.0 ± 5.7°, 28.7 ± 5.9° and 19.0 ± 2.9 mm in male, respectively. In female, they were 26.7 ± 6.1°, 27.0 ± 5.5° and 16.4 ± 2.6 mm, respectively.

Conclusion.

It is safe and feasible to place the iliosacral screw when performing this novel instrumentation. Preoperative CT imaging and 3D reconstructions may help to determine the correct entry point and the trajectory of iliosacral screw.

Level of Evidence: 5
Risk Factors of Impaired Neuropsychologic Outcome in School-Aged Survivors of Neonatal Critical Illness*
Authors: Leeuwen Lisette , Schiller Raisa M. , Rietman André B. , van Rosmalen Joost , Wildschut Enno D. , Houmes Robert Jan M. , Tibboel Dick , IJsselstijn Hanneke
Published: December 2017

Objective:

Until now, long-term outcome studies have focused on general cognitive functioning and its risk factors following neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia. However, it is currently unknown which neuropsychological domains are most affected in these patients and which clinical variables can be used to predict specific neuropsychological problems. This study aimed to identify affected neuropsychological domains and its clinical determinants in survivors of neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia.

Design:

Prospective follow-up study.

Setting:

Tertiary university hospital.

Patients:

Sixty-five 8-year-old survivors of neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia.

Interventions:

None.

Measurements and Main Results:

Intelligence, attention, memory, executive functioning and visuospatial processing were evaluated using validated tests and compared with Dutch reference data. Assessed risk factors of outcome were illness severity indicators, number of anesthetic procedures in the first year of life, and growth at 1 year. Patients had average intelligence (mean intelligence quotient ± sd, 95 ± 16), but significantly poorer sustained attention (mean z score ± sd, –2.73 ± 2.57), verbal (immediate, –1.09 ± 1.27; delayed, –1.14 ± 1.86), and visuospatial memory (immediate, –1.48 ± 1.02; delayed, –1.57 ± 1.01; recognition, –1.07 ± 3.10) than the norm. Extracorporeal membrane oxygenation–treated congenital diaphragmatic hernia patients had significantly lower mean intelligence quotient (84 ± 12) than other neonatal extracorporeal membrane oxygenation patients (94 ± 10) and congenital diaphragmatic hernia patients not treated with extracorporeal membrane oxygenation (100 ± 20). Maximum vasoactive-inotropic score was negatively associated with delayed verbal (B = –0.02; 95% CI, –0.03 to –0.002; p = 0.026) and visuospatial memory (B = –0.01; 95% CI, –0.02 to –0.001; p = 0.024).

Conclusions:

We found memory and attention deficits in 8-year-old neonatal extracorporeal membrane oxygenation and congenital diaphragmatic hernia survivors. The maximum dose of vasoactive medication was negatively associated with verbal and visuospatial memory, which may suggest an effect of early cerebral hypoperfusion in determining these abnormalities.
Endoscopic Corneal Neurotization: Technique and Initial Experience
Authors: Leyngold Ilya , Weller Christopher , Leyngold Mark , Tabor Mark
Published: December 2017

Purpose:

The authors describe a minimally invasive surgical technique to re-establish corneal sensibility in a patient with neurotrophic keratopathy with the supraorbital nerve harvested endoscopically.

Methods:

Pedicled contralateral supraorbital nerve was harvested endoscopically through small eyelid crease and scalp incisions and transferred to the affected eye.

Results:

Endoscopic corneal neurotization was successfully performed with restoration of corneal sensibility and corneal epithelial integrity.

Conclusions:

The use of an endoscope allows for a minimally invasive approach to successful corneal neurotization with the supraorbital nerve.
Induction of chronic migraine phenotypes in a rat model after environmental irritant exposure
Authors: Kunkler Phillip Edward , Zhang LuJuan , Johnson Philip Lee , Oxford Gerry Stephen , Hurley Joyce Harts
Published: December 2017

Air pollution is linked to increased emergency department visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a transient receptor potential channel ankyrin-1 (TRPA1) agonist, or room air by inhalation for 4 days before meningeal blood flow measurements, periorbital cutaneous sensory testing, or other behavioral testing. Touch-induced c-Fos expression in trigeminal nucleus caudalis was compared in animals exposed to room air or acrolein. Spontaneous behavior and olfactory discrimination was examined in open-field testing. Acrolein inhalation exposure produced long-lasting potentiation of blood flow responses to a subsequent TRPA1 agonist and sensitized cutaneous responses to mechanical stimulation. C-Fos expression in response to touch was increased in trigeminal nucleus caudalis in animals exposed to acrolein compared with room air. Spontaneous activity in an open-field and scent preference behavior was different in acrolein-exposed compared with room air–exposed animals. Sumatriptan, an acute migraine treatment blocked acute blood flow changes in response to TRPA1 or transient receptor potential vanilloid receptor-1 agonists. Pretreatment with valproic acid, a prophylactic migraine treatment, attenuated the enhanced blood flow responses observed after acrolein inhalation exposures. Environmental irritant exposure yields an animal model of chronic migraine in which to study mechanisms for enhanced headache susceptibility after chemical exposure.
Gait Deviations Associated With Concussion: A Systematic Review
Authors: Manaseer Thaer S. , Gross Douglas P. , Dennett Liz , Schneider Kathryn , Whittaker Jackie L.
Published: December 2017

Background:

Gait deviations resulting from concussion are important to consider in the diagnosis, treatment progression, and return to activity after a concussion.

Objective:

To identify quantifiable gait deviations associated with concussion across populations and time since injury.

Methods and Materials:

Six electronic databases were systematically searched from January 1974 to September 2016. Studies selected included original data, had an analytic design, and reported a quantifiable gait parameter in individuals who had sustained a concussion as defined by the American Congress of Rehabilitation Medicine or related definitions. Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines were followed. Two independent authors assessed study quality [Downs and Black (DB) criteria] and level of evidence (Oxford Center of Evidence-Based Medicine Model).

Results:

Of 2650 potentially relevant articles, 21 level 4 studies were included. The median DB score was 12/33 (range 10-16). Heterogeneity in gait parameters and timing of postconcussion testing precluded meta-analysis. There is consistent level 4 evidence of increased medial-lateral center-of-mass displacement, and inconsistent level 4 evidence of decreased gait velocity after concussion. Further, there is preliminary level 4 evidence that gait deficits may exist beyond the typical 10-day recovery period and return to activity.

Conclusion:

These findings suggest that individuals who have suffered a concussion may sway more in the frontal plane, and walk slower compared to healthy controls. Consensus about the most important gait parameters for concussion diagnosis and clinical management are lacking. Further, high-quality prospective cohort studies evaluating changes in gait from time of concussion to return to activity, sport, recreation and/or work are needed.
Disruption of the gut-liver axis in the pathogenesis of acute-on-chronic liver failure
Authors: Zhang Tao , Sun Kewei , Wang Ya , Huang Lei , Lang Ren , Jiang Wei
Published: December 2017

Acute-on-chronic liver failure (ACLF) is characterized by organ failure mediated by acute decompensation of cirrhosis. Recent studies have highlighted the importance of the gut-liver axis (GLS) and its association with ACLF pathogenesis. In this review, we discuss the mechanisms related to the alteration of the GLA and their involvement in ACLF pathogenesis and suggest some possible therapeutic options that could modulate the GLA dysfunction. This knowledge may provide information useful for the design of therapeutic strategies for gut dysbiosis and its complications in ACLF.
Successful Treatment of Mediastinal γδ T-Cell Lymphoblastic Lymphoma in a 3-Year-Old Girl by Allogeneic Cord Blood Transplantation
Authors: Hori Daiki , Kobayashi Ryoji , Suzuki Daisuke , Sano Hirozumi , Kiyokawa Nobutaka , Kobayashi Kunihiko
Published: December 2017

A 3-year-old girl presenting with a huge mediastinal tumor and massive pleural effusion, was diagnosed with stage III γδ T-cell lymphoblastic lymphoma (γδ T-LBL) by flow cytometry of effusion cells. Four courses of chemotherapy achieved complete remission, and 5/6 HLA allele-matched cord blood transplantation was performed with success. The patient remains in first complete remission >16 months after transplantation. γδ T-LBL is very rare, especially that of mediastinal origin, and is acknowledged as having an extremely poor clinical outcome. The present case study is the first to report the successful treatment of mediastinal γδ T-LBL in a toddler.
Posterior Reversible Encephalopathy Syndrome: Risk Factors and Impact on the Outcome in Children With Acute Lymphoblastic Leukemia Treated With Nordic Protocols
Authors: Banerjee Joanna S. , Heyman Mats , Palomäki Maarit , Lähteenmäki Päivi , Arola Mikko , Riikonen Pekka V. , Möttönen Merja I. , Lönnqvist Tuula , Taskinen Mervi H. , Harila-Saari Arja H.
Published: December 2017

Posterior reversible encephalopathy syndrome (PRES) in children with acute lymphoblastic leukemia has been increasingly recognized as a clinicoradiological entity. Our aim was to describe the incidence of PRES in pediatric patients with ALL, identify its risk factors, and examine its prognostic importance. For this research, we conducted a systematic, retrospective review of the patient records in a population-based series of children with acute lymphoblastic leukemia (n=643) treated in Finland from 1992 to 2008. Of the patients with ALL, 4.5% (n=29) developed radiologically confirmed PRES, of which 28 cases occurred during induction. Hypertension (P=0.006; odds ratio [OR], 4.10, confidence interval [CI], 1.50-11.25), constipation (P=0.001; OR, 5.60; CI, 2.02-15.52), and >14 days of alkalinization (P=0.017; OR, 3.27; CI, 1.23-8.68) were significant independent risk factors for PRES. One-third of the patients developed epilepsy. Relapses occurred significantly more often in those patients with PRES (P=0.001), which was associated with worse overall survival (P=0.040; 5-year survival=75.9% [60.3%-91.4%] vs. 88.4% [85.8%-90.9%]). Using NOPHO-ALL 92/2000 protocols, PRES is a significant early complication of therapy in ALL, and was associated with a poorer prognosis and significant neurological morbidity.
Spontaneous Regression in a Patient With Infantile Fibrosarcoma
Authors: Sait Sameer Farouk , Danzer Enrico , Ramirez Daniel , LaQuaglia Michael P. , Paul Meyers
Published: December 2017

Infantile fibrosarcoma usually presents as a rapidly growing mass on the extremities or trunk. We describe spontaneous regression in a 5-month-old female infant with biopsy proven, molecularly confirmed, right leg infantile fibrosarcoma currently at 26 months of age with no signs of local recurrence. Previously reported cases of spontaneous regression are reviewed, suggesting a benign clinical course in some cases. Although evidence for spontaneous regression is anecdotal in this rare tumor type, physicians should weigh the risks and benefits of surgery and chemotherapy against watchful waiting.
Nurses' Use of Positive Deviance When Encountering Electronic Health Records-Related Unintended Consequences
Authors: Bristol Alycia A. , Nibbelink Christine W. , Gephart Sheila M. , Carrington Jane M.
Published: December 2017

As organizations adopt electronic health records (EHRs), nurses frequently encounter system barriers and difficulty performing role expectations. This article describes nurses' experiences with unintended consequences emerging from the use of an EHR. In some situations, nurses were positively deviant when encountering unintended consequences relating to EHRs to accomplish patient care or protect patient safety. Nurses engaged in work-arounds to provide patient care when the EHR did not meet their needs, sometimes in positively deviant ways. Qualitative data were collected from 5 open-ended questions at the end of a quantitative survey. Analysis included coding of responses and organization of processes in line with the triangle model, a human factors framework, to identify overarching themes. Five themes emerged: (1) User support after implementation of EHR; (2) User satisfaction with EHR; (3) Communication for patient care, quality, and safety; (4) Effort to complete tasks; and (5) Areas for improvement. Nurses' ability to adopt positive deviance as they experience unintended consequences offers opportunities for organizations to engage nursing perspectives in improving the EHR and engineer it to be more resilient to nursing work.
Genome-based transmission modeling separates imported tuberculosis from recent transmission within an immigrant population
Authors: Ayabina Diepreye , Rønning Janne O , Alfsnes Kristian , Debech Nadia , Brynildsrud Ola B , Arnesen Trude , Norheim Gunnstein , Mengshoel Anne-Torunn , Rykkvin Rikard , Dahle Ulf R , Colijn Caroline , Eldholm Vegard
Published: December 2017

Background

In many countries tuberculosis incidence is low and largely shaped by immigrant populations from high-burden countries. This is the case in Norway, where more than 80 per cent of TB cases are found among immigrants from high-incidence countries. A variable latent period, low rates of evolution and structured social networks make separating import from within-border transmission a major conundrum to TB-control efforts in many low-incidence countries.

Methods

Clinical Mycobacterium tuberculosis isolates belonging to an unusually large genotype cluster associated with people born in the Horn of Africa, have been identified in Norway over the last two decades. We applied modeled transmission based on whole-genome sequence data to estimate infection times for individual patients. By contrasting these estimates with time of arrival in Norway, we estimate on a case-by-case basis whether patients were likely to have been infected before or after arrival.

Results

Independent import was responsible for the majority of cases, but we estimate that about a quarter of the patients had contracted TB in Norway.

Conclusions

This study illuminates the transmission dynamics within an immigrant community. Our approach is broadly applicable to many settings where TB control programs can benefit from understanding when and where patients acquired tuberculosis.
A clustering neural network model of insect olfaction
Authors: Pehlevan Cengiz , Genkin Alexander , Chklovskii Dmitri B.
Published: December 2017

A key step in insect olfaction is the transformation of a dense representation of odors in a small population of neurons - projection neurons (PNs) of the antennal lobe - into a sparse representation in a much larger population of neurons -Kenyon cells (KCs) of the mushroom body. What computational purpose does this transformation serve? We propose that the PN-KC network implements an online clustering algorithm which we derive from the k-means cost function. The vector of PN-KC synaptic weights converging onto a given KC represents the corresponding cluster centroid. KC activities represent attribution indices, i.e. the degree to which a given odor presentation is attributed to each cluster. Remarkably, such clustering view of the PN-KC circuit naturally accounts for several of its salient features. First, attribution indices are nonnegative thus rationalizing rectification in KCs. Second, the constraint on the total sum of attribution indices for each presentation is enforced by a Lagrange multiplier identified with the activity of a single inhibitory interneuron reciprocally connected with KCs. Third, the soft-clustering version of our algorithm reproduces observed sparsity and overcompleteness of the KC representation which may optimize supervised classification downstream.
Rice blast resistance gene Pii is controlled by a pair of NBS-LRR genes Pii-1 and Pii-2
Authors: Takagi Hiroki , Abe Akira , Uemura Aiko , Oikawa Kaori , Utsushi Hiroe , Yaegashi Hiroki , Kikuchi Hideko , Shimizu Motoki , Abe Yoshiko , Kanzaki Hiroyuki , Saito Hiromasa , Terauchi Ryohei , Fujisaki Koki
Published: December 2017

Nucleotide-binding, leucine-rich repeat receptors (NLRs) are conserved cytosolic receptors that recognize pathogen effectors and trigger immunity in plants. Recent studies indicate that NLRs function in pairs. Rice resistance gene Pii has been known to confer resistance against rice blast pathogen Magnaporthe oryzae carrying AVR-Pii. Previously we reported isolation of Pii gene from the rice cultivar Hitomebore (Takagi et al. 2013). To further understand rice components required for Pii-mediated resistance, we screened 5,600 mutant lines of Hitomebore cultivar and identified two mutants that lost Pii resistance without any changes in Pii gene sequence. Application of MutMap-Gap, the whole genome sequencing-based method of mutation identification, to the two mutants revealed that they have mutations in another NLR gene located close to Pii. The F1 plants derived from a cross of the two mutants showed pii phenotype, demonstrating that the newly identified NLR gene is indeed a component of Pii resistance. We thus designate the previously isolated Pii gene as Pii-1 and the newly isolated NLR gene as Pii-2.
Altering brain dynamics with transcranial random noise stimulation
Authors: van der Groen Onno , Wenderoth Nicole , Mattingley Jason B.
Published: December 2017

Random noise can enhance the detectability of weak signals in nonlinear threshold systems, a phenomenon known as stochastic resonance (SR). This concept is not only applicable to single threshold systems but can also be applied to dynamical systems with multiple attractor states, such as observed during the phenomenon of binocular rivalry. Binocular rivalry can be characterized by marginally stable attractor states between which the brain switches in a spontaneous, stochastic manner. The switches are thought to be driven by a combination of neuronal adaptation and noise. Here we used a computational model to predict the effect of noise on perceptual dominance durations when either low-contrast or high-contrast stimuli are presented. Subsequently we compared the model prediction to a series of three experiments where we measured binocular rivalry dynamics when noise (zero-mean Gaussian white noise) was added either to the visual stimulus (Exp. 1) or directly to the visual cortex (Exp. 2 and Exp. 3) by applying transcranial Random Noise Stimulation (tRNS 1mA, 100-640 Hz zero mean Gaussian white noise). We found that adding noise significantly reduced the mixed percept duration (Exp. 1 and Exp. 2). This effect was only present for low-contrast but not for high-contrast visual stimuli which is in line with the model predictions. Our results demonstrate that both central and peripheral noise can influence state-switching dynamics of binocular rivalry under specific conditions (e.g. low visual contrast stimuli), in line with a SR-mechanism.
Biological Self-organisation and Markov blankets
Authors: Palacios Ensor Rafael , Razi Adeel , Parr Thomas , Kirchhoff Michael , Friston Karl
Published: December 2017

Biological self-organisation is a process of spontaneous pattern formation; namely the emergence of coherent and stable systemic configurations that distinguish themselves from their environment. This process can occur at various spatial scales: from the microscopic (giving rise to cells) to the macroscopic (the emergence of organisms). Self-organisation at each level is essential to account for the hierarchical organisation of living organisms (organelles within cells, within tissues, within organs, etc.). In this paper, we pursue the idea that Markov blankets – statistical boundaries separating states that are external to a system from its internal states – emerge at every possible level of the description of the (living) system. Through simulations, we show that the concept of a Markov blanket is fundamental in defining biological systems and underwrites the nature and form of interactions between successive levels of hierarchical structure. We demonstrate the validity of our argument using simulations, based on the normative principle of variational free energy minimisation. Specifically, we adopt a top-down approach to provide a proof of concept for the claim that the self-organisation of Markov blankets (and blankets of blankets) underwrites the self-evidencing, autopoietic behaviour of living systems.
BLINK: A Package for Next Level of Genome Wide Association Studies with Both Individuals and Markers in Millions
Authors: Huang Meng , Liu Xiaolei , Zhou Yao , Summers Ryan M. , Zhang Zhiwu
Published: December 2017

Big data, accumulated from biomedical and agronomic studies, provides the potential to identify genes controlling complex human diseases and agriculturally important traits through genome-wide association studies (GWAS). However, big data also leads to extreme computational challenges, especially when sophisticated statistical models are employed to simultaneously reduce false positives and false negatives. The newly developed Fixed and random model Circulating Probability Unification (FarmCPU) method uses a bin method under the assumption that Quantitative Trait Nucleotides (QTNs) are evenly distributed throughout the genome. The estimated QTNs are used to separate a mixed linear model into a computationally efficient fixed effect model (FEM) and a computationally expensive random effect model (REM), which are then used iteratively. To completely eliminate the computationally expensive REM, we replaced REM with FEM by using Bayesian information criteria. To eliminate the requirement that QTNs be evenly distributed throughout the genome, we replaced the bin method with linkage disequilibrium information. The new method is called Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK). Both real and simulated data analyses demonstrated that BLINK improves statistical power compared to FarmCPU, in addition to a remarkable improvement in computing time. Now, a dataset with half million markers and one million individuals can be analyzed within five hours, compared with one week using FarmCPU.
Physico-chemical properties of co-formulation of insulin with pramlintide
Authors: da Silva Dayana Cabral , Lima Luís Maurício T. R.
Published: December 2017

Since the discovery of amylin its use has been discouraged by the inadequacy of the protocol involving multiple injections in addition to insulin. While a combined fixed-dose formulation is thus highly desirable, it has long been limited due to incompatibility as historically documented. We have investigated the compatibility of regular and fast-acting insulin analogues (Aspart, AspB28, and LisPro, LysB28ProB29) with the amylin analogue pramlintide. Insulin interacts with pramlintide, forming heterodimers as probed by electrospray ionization - ion mobility spectrometry-mass spectrometry. While their interaction is likely to delay the amyloid aggregation of pramlintide in phosphate-buffered solution pH 7.0, they do not prevent aggregation at this condition. At acidic sodium acetate solution pH 5.0, combination of pramlintide and the fast-acting insulin analogues become stable against amyloid aggregation. The co-formulated product at high concentration of both pramlintide (600 μg/mL,150 μM) and LisPro insulin (50 IU/mL, 300 μM) showed also stability against amyloid aggregation. These data indicate a potential for the development of a co-formulation of fast-acting LisPro insulin with pramlintide, which could bring benefits for the combined therapy.

Abbreviations

IAPP,

islet amyloid polypeptide;

ESI-IMS-MS,

Electrospray Ionization–Ion Mobility Spectrometry–Mass Spectrometry.
Defining Major Depressive Disorder Cohorts Using the EHR: Multiple Phenotypes Based on ICD-9 Codes and Medication Orders
Authors: Ingram Wendy Marie , Baker Anna M. , Bauer Christopher R. , Brown Jason P. , Goes Fernando S. , Larson Sharon , Zandi Peter P.
Published: December 2017

Background

Major Depressive Disorder (MDD) is one of the most common mental illnesses and a leading cause of disability worldwide. Electronic Health Records (EHR) allow researchers to conduct unprecedented large-scale observational studies investigating MDD, its disease development and its interaction with other health outcomes. While there exist methods to classify patients as clear cases or controls, given specific data requirements, there are presently no simple, generalizable, and validated methods to classify an entire patient population into varying groups of depression likelihood and severity.

Methods

We have tested a simple, pragmatic electronic phenotype algorithm that classifies patients into one of five mutually exclusive, ordinal groups, varying in depression phenotype. Using data from an integrated health system on 278,026 patients from a 10-year study period we have tested the convergent validity of these constructs using measures of external validation, including patterns of psychiatric prescriptions, symptom severity, indicators of suicidality, comorbidity, mortality, health care utilization, and polygenic risk scores for MDD.

Results

We found consistent patterns of increasing morbidity and/or adverse outcomes across the five groups, providing evidence for convergent validity.

Limitations

The study population is from a single rural integrated health system which is predominantly white, possibly limiting its generalizability.

Conclusion

Our study provides initial evidence that a simple algorithm, generalizable to most EHR data sets, provides categories with meaningful face and convergent validity that can be used for stratification of an entire patient population.
Microfluidic isoform sequencing shows widespread splicing coordination in the human transcriptome
Authors: Tilgner Hagen , Jahanbani Fereshteh , Gupta Ishaan , Collier Paul , Wei Eric , Rasmussen Morten , Snyder Michael
Published: December 2017

Understanding transcriptome complexity is crucial for understanding human biology and disease. Technologies such as Synthetic long-read RNA sequencing (SLR-RNA-seq) delivered 5 million isoforms and allowed assessing splicing coordination. Pacific Biosciences and Oxford Nanopore increase throughput also but require high input amounts or amplification. Our new droplet-based method, sparse isoform sequencing (spISO-seq), sequences 100k–200k partitions of 10–200 molecules at a time, enabling analysis of 10–100 million RNA molecules. SpISO-seq requires less than 1 ng of input cDNA, limiting or removing the need for prior amplification with its associated biases. Adjusting the number of reads devoted to each molecule reduces sequencing lanes and cost, with little loss in detection power. The increased number of molecules expands our understanding of isoform complexity. In addition to confirming our previously published cases of splicing coordination (e.g.,BIN1), the greater depth reveals many new cases, such asMAPT. Coordination of internal exons is found to be extensive among protein coding genes: 23.5%–59.3% (95% confidence interval) of highly expressed genes with distant alternative exons exhibit coordination, showcasing the need for long-read transcriptomics. However, coordination is less frequent for noncoding sequences, suggesting a larger role of splicing coordination in shaping proteins. Groups of genes with coordination are involved in protein–protein interactions with each other, raising the possibility that coordination facilitates complex formation and/or function. We also find new splicing coordination types, involving initial and terminal exons. Our results provide a more comprehensive understanding of the human transcriptome and a general, cost-effective method to analyze it.
What jesus says to public administration
Authors: Lance deHaven-Smith
Published: December 2017

This essay argues that the teachings and ethos of Jesus are needed in public administration to address a potentially fatal weakness in modern industrial republics. The latter are increasingly prone to domestic tyranny and international imperialism, because the values that once constrained them, and which once were thought to be self-evident, have been traced to Christian doctrines discredited by science. The first half of the essay chronicles the failure of the West either to live well without these values, or to find an alternative foundation for them. The second half of the essay shows that this dilemma can be overcome by differentiating the teachings of Jesus from the doctrines of Christianity
The virtues of politics in fearful times
Authors: Spicer Michael W.
Published: December 2017

While many warn about the failures of politics, this article argues that politics serves to resolve conflicts of interests and values among us in a manner that limits the use of violence and also protects and fosters value pluralism and freedom. Public administration scholars often look to science to improve governance but science cannot resolve our many conflicting ends and values, nor can it take proper account of the freedom and resulting sheer unpredictability that we have come to experience within our own tradition of politics. It is argued that the practice of politics requires not a science of governance, but simply a certain kind of toleration, namely a willingness to hear the other side and to engage in practices of adversary argument. Implications for the "politics of fear" are also discussed.
Examining absenteeism in the public and non-profit sectors
Authors: Edwards Vickie L.
Published: December 2017

Using the Steers and Rhodes (1978) model of absenteeism behavior, this paper examines ability to attend and attendance motivation factors for public and non-profit managers. Attendance motivation factors utilized in this study include public service motivation, job satisfaction, and organizational commitment. T-tests and OLS regressions suggest that there are significant differences between absenteeism in the public and non-profit sectors and between genders. The results also suggest that organizational commitment, especially in terms of stakeholdership, is negatively associated with absenteeism. Perceptions of flexibility are found to be positively associated with the number of days missed.
Training top civil servants in turbulent environments: An ongoing struggle for curriculum
Authors: Halley Alexis A.
Published: December 2017

This article provides a historical literature review and exploratory descriptive case study of one U.S. Federal agencyʼs efforts to design an appropriate government-wide leadership development curriculum for incumbent top or senior civil servants. The U.S. Federal Executive Institute was founded in 1968, it spans the 20th and 21st centuries, it illustrates changes in the compact that exists between government and its top civil servants over time, and it illustrates challenges this agency confronts addressing the task of interagency leadership development. The main findings are three continuities and three discontinuities between curriculum development then and now. Conclusions outline issues for future interdisciplinary research to inform the intellectual roots for 21st century curricula aligned to emerging roles and the challenges top career executives actually confront.