bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiscale Modeling of Gene–Behavior Associations in an Artificial Neural Network Model of Cognitive Development
Authors: Thomas Michael S. C. , Forrester Neil A. , Ronald Angelica
Published: April 2015

In the multidisciplinary field of developmental cognitive neuroscience, statistical associations between levels of description play an increasingly important role. One example of such associations is the observation of correlations between relatively common gene variants and individual differences in behavior. It is perhaps surprising that such associations can be detected despite the remoteness of these levels of description, and the fact that behavior is the outcome of an extended developmental process involving interaction of the whole organism with a variable environment. Given that they have been detected, how do such associations inform cognitive‐level theories? To investigate this question, we employed a multiscale computational model of development, using a sample domain drawn from the field of language acquisition. The model comprised an artificial neural network model of past‐tense acquisition trained using the backpropagation learning algorithm, extended to incorporate population modeling and genetic algorithms. It included five levels of description—four internal: genetic, network, neurocomputation, behavior; and one external: environment. Since the mechanistic assumptions of the model were known and its operation was relatively transparent, we could evaluate whether cross‐level associations gave an accurate picture of causal processes. We established that associations could be detected between artificial genes and behavioral variation, even under polygenic assumptions of a many‐to‐one relationship between genes and neurocomputational parameters, and when an experience‐dependent developmental process interceded between the action of genes and the emergence of behavior. We evaluated these associations with respect to their specificity (to different behaviors, to function vs. structure), to their developmental stability, and to their replicability, as well as considering issues of missing heritability and gene–environment interactions. We argue that gene–behavior associations can inform cognitive theory with respect to effect size, specificity, and timing. The model demonstrates a means by which researchers can undertake multiscale modeling with respect to cognition and develop highly specific and complex hypotheses across multiple levels of description.
Umbilical cord blood transplantation in adults with advanced hodgkin's disease: high incidence of post‐transplant lymphoproliferative disease
Authors: Piñana José Luis , Sanz Jaime , Esquirol Albert , Martino Rodrigo , Picardi Alessandra , Barba Pere , Parody Rocio , Gayoso Jorge , Montesinos Pau , Guidi Stefano , Terol Maria José , Moscardó Federico , Solano Carlos , Arcese William , Sanz Miguel A. , Sierra Jorge , Sanz Guillermo ,   GETH GITMO groups
Published: April 2015

We report the outcome of 30 consecutive patients with Hodgkin disease (HD) who underwent single‐unit UCBT. Most (90%) patients had failed previous autologous hematopoietic stem cell transplantation. The conditioning regimens were based on combinations of thiotepa, busulfan, cyclophosphamide or fludarabine, and antithymocyte globulin. The cumulative incidence (CI) of myeloid engraftment was 90% [95% confidence interval (C.I.), 74–98%] with a median of 18 d (range, 10–48). CI of acute graft‐versus‐host disease (GvHD) grades II–IV was 30% (95% C.I., 17–44%), while the incidence of chronic GVHD was 42% (95% C.I., 23–77%). The non‐relapse mortality (NRM) at 100 d and 4 yr was 30% (95% C.I., 13–46%) and 47% (95% C.I., 29–65%), respectively. EBV‐related post‐transplant lymphoproliferative disease (EBV‐PTLD) accounted for more than one‐third of transplant‐related death, with an estimate incidence of 26% (95% C.I., 9–44). The incidence of relapse at 4 yr was 25% (95% C.I., 9–42%). Four‐year event‐free survival (EFS) and overall survival (OS) were 28% and 30%, respectively. Despite a high NRM and an unexpected high incidence of EBV‐PTLD, UCBT in heavily pretreated HD patients is an option for patients lacking a suitable adult donor, provided the disease is not in refractory relapse.
Complex alterations in microglial M1/M2 markers during the development of epilepsy in two mouse models
Authors: Benson Melissa J. , Manzanero Silvia , Borges Karin
Published: April 2015

Objective

To characterize the changes in microglial proinflammatory M1 and antiinflammatory M2 marker expression during epileptogenesis in the chronic pilocarpine and intrahippocampal kainate models.

Methods

M1‐activated microglia express proinflammatory cytokines driving infiltration of cells, whereas M2‐activated microglia are more reparative, promoting phagocytosis of debris and expression of proteins associated with cellular stability and repair. Microglial markers were characterized as acute (3 days after status epilepticus [SE]), early chronic (21 days post‐SE), and late chronic epileptic (5–12 months post‐SE) time points. Following pilocarpine‐SE, microglial markers were assessed by flow cytometry. Quantitative real‐time polymerase chain reaction (RT‐PCR) was used to measure messenger RNA (mRNA) levels of selected M1 (interleukin [IL] 1β, tumor necrosis factor α [TNFα] cluster of differentiation [CD],CD16, and CD86), interleukin‐6 [IL‐6], interleukin‐12 [IL‐12], Fc receptors 16, and CD86) and M2 (arginase 1 [Arg1], chitinase‐3‐like protein [Ym1], found in inflammatory zone [FIZZ‐1] [FIZZ‐1], mannose receptor C type‐1 [CD206], interleukin‐4 [IL‐4], and interleukin‐10 (IL‐10)) markers in both models. Video–electroencephalography (EEG) recordings were used to quantify late chronic seizure frequency.

Results

Three days post‐SE microglia in the pilocarpine model expressed M1 and M2 markers, but only M1 markers were upregulated after kainate‐induced SE. After 3 weeks, M1/M2 marker expression was largely ablated in the hippocampal formation of both models. Small mRNA level increases of CD11b, glial fibrillary acidic protein (GFAP), and IL‐1β were found in the pilocarpine model, consistent with IL‐1β contributing to spontaneous seizures, whereas mRNA levels of TNFα and Ym1 were decreased. In the late chronic phase, some M1/M2 markers, IL‐1β, TNFα, Arg1, Ym1, and CD206, resurged in the kainate, but not pilocarpine model, which may reflect and/or contribute to highly frequent seizures in kainate‐SE mice.

Significance

The common M1 upregulation acutely post‐SE may signal a role early in epileptogenesis, with a more pure “inflamed” central nervous system state after kainate‐SE, potentially contributing to the development of more frequent seizures. The difference may also be due to the contribution of peripheral inflammation after pilocarpine injection. In summary, the microglial inflammatory response during epileptogenesis is complex, varies between models, and appears to correlate with chronic seizure frequency.
Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare condition caused by mutations in ASAH1
Authors: Rubboli Guido , Veggiotti Pierangelo , Pini Antonella , Berardinelli Angela , Cantalupo Gaetano , Bertini Enrico , Tiziano Francesco Danilo , D'Amico Adele , Piazza Elena , Abiusi Emanuela , Fiori Stefania , Pasini Elena , Darra Francesca , Gobbi Giuseppe , Michelucci Roberto
Published: April 2015

Objective

To present the clinical features and the results of laboratory investigations in three patients with spinal muscular atrophy associated with progressive myoclonic epilepsy (SMA‐PME), a rare condition caused by mutations in the N‐acylsphingosine amidohydrosilase 1 (ASAH1) gene.

Methods

The patients were submitted to clinical evaluation, neurophysiologic investigations (that included wakefulness and sleep electroencephalography [EEG], video‐polygraphic recording with jerk‐locked back‐averaging, multimodal evoked potentials, and electromyography), brain magnetic resonance imaging (MRI), biochemical screening, muscle and skin biopsies, and molecular genetic analysis.

Results

The main clinical features were onset in childhood with proximal muscular weakness, generalized epilepsy with absences and myoclonic seizures, cognitive impairment of variable degree; the course was progressive with muscle wasting and uncontrolled epileptic seizures. In one patient, earlier onset before the age of 2 years was associated with a more complex clinical picture, with abnormal eye movements, progressive cognitive impairment, and a more rapid and severe course. EEG/polygraphic data were consistent with PME, demonstrating generalized spike‐and‐wave discharges, evidence of positive and negative myoclonia, and prominent photosensitivity. In one patient, transcranial magnetic stimulation showed a hyperexcitable motor cortex, whereas somatosensory evoked potentials were unaffected. Possible involvement of the central acoustic and visual pathways was suggested by abnormal auditory and visual evoked potentials. Muscle biopsies showed typical signs of neurogenic damage. Molecular genetic analysis showed mutations of the ASAH1 gene.

Significance

Our data indicate that SMA‐PME associated with ASAH1 mutations is a genetically distinct condition with specific clinical and neurophysiologic features. Further studies are warranted to explore the role of the ASAH1 gene in muscle and brain function.
Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation
Authors: Kobayashi Taeko , Iwamoto Yumiko , Takashima Kazuhiro , Isomura Akihiro , Kosodo Yoichi , Kawakami Koichi , Nishioka Tomoki , Kaibuchi Kozo , Kageyama Ryoichiro
Published: April 2015

Hairy and enhancer of split 1 (Hes1), a basic helix‐loop‐helix transcriptional repressor protein, regulates the maintenance of neural stem/progenitor cells by repressing proneural gene expression via Notch signaling. Previous studies showed that Hes1 expression oscillates in both mouse embryonic stem cells and neural stem cells, and that the oscillation contributes to their potency and differentiation fates. This oscillatory expression depends on the stability of Hes1, which is rapidly degraded by the ubiquitin/proteasome pathway. However, the detailed molecular mechanisms governing Hes1 stability remain unknown. We analyzed Hes1‐interacting deubiquitinases purified from mouse embryonic stem cells using an Hes1‐specific antibody, and identified the ubiquitin‐specific protease 27x (Usp27x) as a new regulator of Hes1. We found that Hes1 was deubiquitinated and stabilized by Usp27x and its homologs ubiquitin‐specific protease 22 (Usp22) and ubiquitin‐specific protease 51 (Usp51). Knockdown of Usp22 shortened the half‐life of Hes1, delayed its oscillation, and enhanced neuronal differentiation in mouse developing brain, whereas mis‐expression of Usp27x reduced neuronal differentiation. These results suggest that these deubiquitinases modulate Hes1 protein dynamics by removing ubiquitin molecules, and thereby regulate neuronal differentiation of stem cells.
In vivo processing and release into the circulation of GFP fusion protein in arginine vasopressin enhanced GFP transgenic rats: response to osmotic stimulation
Authors: Satoh Keita , Oti Takumi , Katoh Akiko , Ueta Yoichi , Morris John F. , Sakamoto Tatsuya , Sakamoto Hirotaka
Published: April 2015

Arginine vasopressin (AVP) is a neurohypophysial hormone synthesized as a part of a prepropeptide precursor containing the signal peptide, AVP hormone, AVP‐associated neurophysin II and copeptin in the hypothalamic neurosecretory neurons. A transgenic (Tg) rat line expressing the AVP‐eGFP fusion gene has been generated. To establish the AVP‐eGFP Tg rat as a unique model for an analysis of AVP dynamics in vivo, we first examined the in vivo molecular dynamics of the AVP‐eGFP fusion gene, and then the release of GFP in response to physiological stimuli. Double immunoelectron microscopy demonstrated that GFP was specifically localized in neurosecretory vesicles of AVP neurons in this Tg rat. After stimulation of the posterior pituitary with high potassium we demonstrated the exocytosis of AVP neurosecretory vesicles containing GFP at the ultrastructural level. Biochemical analyses indicated that the AVP‐eGFP fusion gene is subjected to in vivo post‐translational modifications like the native AVP gene, and is packaged into neurosecretory vesicles as a fusion protein: copeptin1–14‐GFP. Moreover, GFP release into the circulating blood appeared to be augmented after osmotic stimulation, like native AVP. Thus, here we show for the first time the in vivo molecular processing of the AVP‐eGFP fusion gene and stimulated secretion after osmotic stimulation in rats. Because GFP behaved like native AVP in the hypothalamo‐pituitary axis, and in particular was released into the circulation in response to a physiological stimulus, the AVP‐eGFP Tg rat model appears to be a powerful tool for analyzing neuroendocrine systems at the organismal level.
Response of soil carbon dioxide fluxes, soil organic carbon and microbial biomass carbon to biochar amendment: a meta‐analysis
Authors: Liu Shuwei , Zhang Yaojun , Zong Yajie , Hu Zhiqiang , Wu Shuang , Zhou Jie , Jin Yaguo , Zou Jianwen
Published: April 2015

Biochar as a carbon‐rich coproduct of pyrolyzing biomass, its amendment has been advocated as a potential strategy to soil carbon (C) sequestration. Updated data derived from 50 papers with 395 paired observations were reviewed using meta‐analysis procedures to examine responses of soil carbon dioxide (CO2) fluxes, soil organic C (SOC), and soil microbial biomass C (MBC) contents to biochar amendment. When averaged across all studies, biochar amendment had no significant effect on soil CO2 fluxes, but it significantly enhanced SOC content by 40% and MBC content by 18%. A positive response of soil CO2 fluxes to biochar amendment was found in rice paddies, laboratory incubation studies, soils without vegetation, and unfertilized soils. Biochar amendment significantly increased soil MBC content in field studies, N‐fertilized soils, and soils with vegetation. Enhancement of SOC content following biochar amendment was the greatest in rice paddies among different land‐use types. Responses of soil CO2 fluxes and MBC to biochar amendment varied with soil texture and pH. The use of biochar in combination with synthetic N fertilizer and waste compost fertilizer led to the greatest increases in soil CO2 fluxes and MBC content, respectively. Both soil CO2 fluxes and MBC responses to biochar amendment decreased with biochar application rate, pyrolysis temperature, or C/N ratio of biochar, while each increased SOC content enhancement. Among different biochar feedstock sources, positive responses of soil CO2 fluxes and MBC were the highest for manure and crop residue feedstock sources, respectively. Soil CO2 flux responses to biochar amendment decreased with pH of biochar, while biochars with pH of 8.1–9.0 had the greatest enhancement of SOC and MBC contents. Therefore, soil properties, land‐use type, agricultural practice, and biochar characteristics should be taken into account to assess the practical potential of biochar for mitigating climate change.
Effects of fat replacement and fibre addition on the texture, sensory acceptance and structure of sucrose‐free chocolate
Authors: Rezende Natália V. , Benassi Marta T. , Vissotto Fernanda Z. , Augusto Pedro P. C. , Grossmann Maria V. E.
Published: April 2015

Dietary fibre has been employed as a sucrose and fat replacement in chocolates and can influence the physical and sensory characteristics of the resulting product. Formulations of sucrose‐free chocolates were developed with the addition of inulin and β‐glucan concentrate as partial substitutes for cocoa butter using a mixture design. The effects of the combinations of the three ingredients provided for the design on the texture, microstructure and sensory acceptance of the chocolates were investigated. The substitution of cocoa butter for inulin or β‐glucan concentrate decreased the hardness of the chocolates. It was possible to replace 10 g of cocoa butter in a 100‐g control formulation with inulin and still maintain good acceptance, while this same substitution with β‐glucan resulted in less acceptable chocolate, with a mean score of 6.4 on a scale from 0 to 10. Scanning electron microscopy (SEM) was used to investigate the effects of fibre addition by observing the developed microstructure.
Viscoelastic properties and textural characterisation of high methoxyl pectin of hawthorn (Crataegus pubescens) in a gelling system
Authors: Linares‐García José Antonio , Ramos‐Ramírez Emma Gloria , Salazar‐Montoya Juan Alfredo
Published: April 2015

The viscoelastic behaviour and texture profile of gels composed of the high methoxyl pectin in hawthorn (HMPH) were studied, and these gels were compared with commercial citrus gels (HMPC). The values of G′ (elastic component) for the HMPH and HMPC gels (1% pectin and pH 3.0) were 2567 and 1177 Pa, respectively, and the values of G″ (viscous component) were 494 and 253, respectively. Because G′ > G″, both of these gels exhibit viscoelastic solid behaviour with predominant elastic characteristics. The viscoelastic behaviours of the gels were analysed using the Burger model. The texture analysis demonstrated that the hardness of the HMPH gels was almost 10‐fold higher than that of the HMPC gels. In addition, the gumminess and chewiness of the HMPH gels were 31.2‐ and 46.1‐fold higher than those of the HMPC gels, respectively. These results could likely contribute to the utilisation of HMPH pectins.
Development of an extruded micronutrient delivery vehicle for the fortification of nixtamalised maize with chelated iron at the point of wet milling
Authors: Torres Pablo C. , Flores Fátima E. , Andrade Juan E.
Published: April 2015

The use of high‐temperature extrusion for the development of a micronutrient delivery vehicle (MDV), made of rice and maize (1:1 w/w), as part of a fortification technology for traditional nixtamalised maize (NM) masa at the point of use was evaluated. A Welly puffing extruder and a peristaltic pump were used to establish a uniform extrusion process for MDVs containing 302 ± 13 mg kg−1 of NaFeEDTA or 656 ± 8 mg kg−1 of ferrous bisglycinate. After manual premixing (30 s) of MDVs with NM (1:20 or 1:40 MDV:NM) and grinding with a pilot scale burr mill (5 min), iron distribution in masa was variable, ranging 3–21% RSD within sections of individual 2‐kg batches. Kneading (5 min) shortly after grinding resulted in uniformed iron distribution (<4% RSD). Despite the iron source and fortification level, fortified NM masa was harder and darker than control after 8‐h storage at room temperature; however, these changes require further sensory evaluation.
Changes in the physical properties of honey powder during storage
Authors: Samborska Katarzyna , Langa Elwira , Bakier Sławomir
Published: April 2015

Honey powders produced by spray drying with the addition of Arabic gum and sodium caseinate were characterised in terms of the influence of storage time on the following physical properties: particle size, moisture content, water activity, bulk density, flowability and hygroscopicity. The storage affected those properties; after 12 weeks of storage, particle size decreased (except Arabic gum powder treated as a control sample), moisture content and water activity increased, hygroscopicity decreased. Changes in bulk density, particle size and moisture content caused the rise of Hausner ratio value; however, the powders were still characterised by a very good flow properties and low cohesiveness. The colour of reconstituted powders was also affected by storage; in most of samples, the darkening, reduction in redness and yellowness were observed. Colour parameters were the most stable in powders obtained with the addition of 2% w/w of sodium caseinate.
Tetrahymena Expresses More than a Hundred Proteins with Lipid‐binding MORN Motifs that can Differ in their Subcellular Localisations
Authors: Habicht Jörn , Woehle Christian , Gould Sven B.
Published: April 2015

Proteins with membrane occupation and recognition nexus (MORN) motifs are associated with cell fission in apicomplexan parasites, chloroplast division in Arabidopsis and the motility of sperm cells. We found that ciliates are among those that encode the largest variety of MORN proteins. Tetrahymena thermophila expresses 129 MORN protein‐encoding genes, some of which are specifically up‐regulated during conjugation. A lipid‐binding assay underpins the assumption that the predominant function of MORN motifs themselves is to confer the ability of lipid binding. The localisation of four MORN candidate proteins with similar characteristics highlights the functional diversity of this group especially in ciliates.
Identification and fine mapping of quantitative trait loci for the number of vascular bundle in maize stem
Authors: Huang Cheng , Chen Qiuyue , Xu Guanghui , Xu Dingyi , Tian Jinge , Tian Feng
Published: April 2015

Studies that investigated the genetic basis of source and sink related traits have been widely conducted. However, the vascular system that links source and sink received much less attention. When maize was domesticated from its wild ancestor, teosinte, the external morphology has changed dramatically; however, less is known for the internal anatomy changes. In this study, using a large maize‐teosinte experimental population, we performed a high‐resolution quantitative trait locus (QTL) mapping for the number of vascular bundle in the uppermost internode of maize stem. The results showed that vascular bundle number is dominated by a large number of small‐effect QTLs, in which a total of 16 QTLs that jointly accounts for 52.2% of phenotypic variation were detected, with no single QTL explaining more than 6% of variation. Different from QTLs for typical domestication traits, QTLs for vascular bundle number might not be under directional selection following domestication. Using Near Isogenic Lines (NILs) developed from heterogeneous inbred family (HIF), we further validated the effect of one QTL qVb9‐2 on chromosome 9 and fine mapped the QTL to a 1.8‐Mb physical region. This study provides important insights for the genetic architecture of vascular bundle number in maize stem and sets basis for cloning of qVb9‐2.
Detecting, Preventing, and Responding to “Fraudsters” in Internet Research: Ethics and Tradeoffs
Authors: Teitcher Jennifer E. F. , Bockting Walter O. , Bauermeister José A. , Hoefer Chris J. , Miner Michael H. , Klitzman Robert L.
Published: April 2015

Research that recruits and surveys participants online is increasing, but is subject to fraud whereby study respondents — whether eligible or ineligible — participate multiple times. Online Internet research can provide investigators with large sample sizes and is cost efficient. Internet-based research also provides distance between the researchers and participants, allowing the participant to remain confidential and/or anonymous, and thus to respond to questions freely and honestly without worrying about the stigma associated with their answers. However, increasing and recurring instances of fraudulent activity among subjects raise challenges for researchers and Institutional Review Boards (IRBs). The distance from participants, and the potential anonymity and convenience of online research allow for individuals to participate easily more than once, skewing results and the overall quality of the data.
On the Justifiability of ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing
Authors: May Thomas
Published: April 2015

In spring 2013 the American College of Medical Genetics and Genomics (ACMG) Working Group on Incidental Findings in Clinical Exome and Genome Sequencing (hereafter “Working Group”) released a report of “Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing,” the culmination of a three-year long consensus project. The Working Group recommended that a number of incidental findings, which they define as “the results of a deliberate search for pathogenic or likely pathogenic alterations in genes that are not apparently relevant to a diagnostic indication for which the sequencing test was ordered,” be returned to clinicians (and patients) independent of patient preferences. The Working Group recognized that their recommendations may violate existing ethical norms, but believe this is justified by a fiduciary duty on the part of clinicians and laboratory personnel to prevent harm by warning patients about certain findings, a duty they claim “supersedes concerns about autonomy.”
Lessons Learned from the Expansion of Naloxone Access in Massachusetts and North Carolina
Authors: Davis Corey S. , Walley Alexander Y. , Bridger Colleen M.
Published: April 2015

States are rapidly modifying law and policy to increase access to the opioid antidote naloxone, and the provision of naloxone rescue kits (NRK) for use in the event of overdose is becoming increasingly common. As of late 2014 the majority of states had passed laws increasing naloxone access, and nearly as many have modified emergency responder scope of practice protocols to permit Emergency Medical Technicians (EMTs) and law enforcement officers to administer the medication. While the text of these laws is generally similar, their implementation varies among states.

This article outlines experiences and lessons learned from two diverse states, Massachusetts and North Carolina. In Massachusetts naloxone access initiatives were well underway before formal legislative action occurred, while in North Carolina the passage of a naloxone access law served as a catalyst for the creation of new programs and facilitated the scale-up of existing ones. In both states legislative action was necessary to permit the prescription and dispensing of naloxone to the friends and family members of people who use opioids, a key legal change.
The Role of Law in Supporting Secondary Uses of Electronic Health Information
Authors: Ramanathan Tara , Schmit Cason , Menon Akshara , Fox Chanelle
Published: April 2015

For decades, health information has been collected and shared for health care delivery and public health purposes. While the “primary use” of patient data for providing direct health care services is the cornerstone of health care practice, health departments rely on data sharing for research and analysis to support disease prevention and health promotion in the population. As the U.S. health system undergoes a digital revolution, health information that was previously captured in paper form now can be captured electronically. Electronic health information (EHI) has transformed the efficiency, capacity, and functions of the U.S. health system. For this reason, there is increased attention to the “secondary use” of electronic patient data for public health uses, including disease reporting and investigation, syndromic surveillance, and patient-specific or population-level communications about health conditions and their associated risk factors. Secondary uses may also encompass clinical research, licensure, and payment for services.
The Health in All Policies (HiAP) Approach and the Law: Preliminary Lessons from California and Chicago
Authors: Polsky Claudia , Stagg Kendall , Gakh Maxim , Bozlak Christine T.
Published: April 2015

“Health in All Policies” (HiAP) is the latest manifestation of an ecological approach to public health enhancement — one that recognizes connections between health and other sectors, and that socioeconomic determinants of health are significant. HiAP is related to other holistic, prevention-oriented approaches to collective health, such as the use of Health Impact Assessments to evaluate the health externalities of pending government decisions. Yet HiAP is unique. It goes beyond evaluation of specific projects and policies, and embodies a distinct approach to cross-sectoral public health work.
From Beginning to End: The Importance of Evidence-Based Policymaking in Vaccination Mandates
Authors: Orenstein Daniel G. , Yang Y. Tony
Published: April 2015

Used appropriately, reliance on science distinguishes public health from policymaking driven more by theory and opinion and enhances trust in public health interventions. Evidence-based vaccine policymaking aims to control communicable disease by urging decision makers to base policies on the best available evidence rather than politics or personal views. The results of this approach, such as smallpox eradication, have been dramatic. Historically, mandatory childhood vaccination has been perhaps the most successful evidence-based tool in combating many epidemics. Philosophically, vaccination mandates correspond to the legal system’s dual role in codifying what society deems undesirable behavior (non-vaccination) and declaring beneficial social norms and values consistent with understandings of the social contract. Despite their effectiveness and philosophical grounding, vaccination mandates present serious legal and ethical questions. Public health policymakers have a continuing responsibility to rely on evidence not only as a basis for generating policy, but also for evaluating and improving elements of its legal design.
The effect of pre‐tectonic reaction and annealing extent on behaviour during subsequent deformation: insights from paired shear zones in the lower crust of Fiordland, New Zealand
Authors: Smith J. R. , Piazolo S. , Daczko N. R. , Evans L.
Published: April 2015

Granulite facies pargasite orthogneiss is partially to completely reacted to garnet granulite either side of narrow (<20 mm) felsic dykes, in Fiordland, New Zealand, forming ~10–80 mm wide garnet reaction zones. The metamorphic reaction changed the abundance of minerals, and their shape and grain size distribution. The extent of reaction and annealing (temperature‐related coarsening and nucleation) is greatest close to the dykes, whereas further away the reaction is incomplete. As a consequence, grain size and the abundance of garnet decreases away from the felsic dykes over a few centimetres. The aspect ratios of clusters of S1 pyroxene and pargasite in the orthogneiss, which are variably reacted to post‐S1 garnet, decrease from high in the host, to near equidimensional close to the dyke. Post‐reaction deformation localized in the fine‐grained partially reacted areas. This produced a pattern of ‘paired’ shear zones located at the outer parts of the garnet reaction zone. Our study shows that grain size sensitive deformation occurs where the grain size is sufficiently reduced by metamorphic reaction. The weakening of the rock due to the change in grain size distribution outweighs the addition of nominally stronger garnet to the assemblage.
Fever, abdominal distension and hepatomegaly
Authors: Shao Ya‐Nan , Tang Lan‐Fang
Published: April 2015

See Answer
Total tract nutrient digestion and milk fatty acid profile of dairy cows fed diets containing different levels of whole raw soya beans
Authors: Venturelli B. C. , de Freitas Júnior J. E. , Takiya C. S. , de Araújo A. P. C. , Santos M. C. B. , Calomeni G. D. , Gardinal R. , Vendramini T. H. A. , Rennó F. P.
Published: April 2015

Whole oilseeds such as soya beans have been utilized in dairy rations to supply additional fat and protein. However, antinutritional components contained in soya beans, such as trypsin inhibitors and haemagglutinins (lectins) may alter digestibility of nutrients and consequently affect animal performance. The objective of the present experiment was to quantify the effect of different levels of whole raw soya beans in diets of dairy cows on nutrient intake, total tract digestion, nutrient balances and milk yield and composition. Sixteen mid to late‐lactation cows (228 ± 20 days in milk; mean ± SD) were used in four replicated 4 × 4 Latin square design experiment with 21‐d periods. Cows were assigned to each square according to milk yield and DIM. The animals were randomly allocated to treatments: control (without soya beans addition; CO), WS9, WS18 and WS27, with addition of 9%, 18% and 27% of whole raw soya bean in diet on a dry matter (DM) basis respectively. All diets contained identical forage and concentrate components and consisted of maize silage and concentrate based on ground corn and soya beans at a ratio of 60:40. There were no differences in OM, CP, NDF and NEL intakes (kg/day and MJ/day) among the treatments (p > 0.05). However, DM and NFC intakes were negatively affected (p = 0.04 and p < 0.01, respectively) and ether extract (EE) intake was positively affected (p < 0.01). Total tract digestion increased linearly with whole raw soya beans for EE (p < 0.01) and NDF (p = 0.01). The excretion (kg/day) of digested soya beans grains increased linearly according to addition of whole raw soya beans. However, the nutritive characteristics of excreted grains were not altered. Milk (kg), milk lactose (kg) and protein (kg) yield decreased linearly (p < 0.01, p < 0.01 and p = 0.04, respectively) milk fat content (%) increased linearly (p < 0.01) with whole raw soya beans inclusion. Increasing addition of whole raw soya beans affected milk fatty acid profile with a linear decrease of cis‐9‐trans 11CLA and total saturated FA; and linear increase of total unsaturated and C18:3 FA. Energy balance was positively affected (p = 0.03) by whole raw soya beans as well as efficiency of NEL milk/DE intake (p = 0.02). Nitrogen balance and microbial protein synthesis were not affected by whole raw soya beans. Increasing doses of whole raw soya beans decreased dry matter intake and milk yield, however, led to an increase of unsaturated acids in milk and higher milk fat concentration.
Notational Variants and Invariance in Linguistics
Authors: Johnson Kent
Published: April 2015

This article argues that the much‐maligned ‘notational variants’ of a given formal linguistic theory play a role similar to alternative numerical measurement scales. Thus, they can be used to identify the invariant components of the grammar; i.e., those features that do not depend on the choice of empirically equivalent representation. Treating these elements as the ‘meaningful’ structure of language has numerous consequences for the philosophy of science and linguistics. I offer several such examples of how linguistic theorizing can profit from adopting a measurement‐theoretic viewpoint. The first concerns a measurement‐theoretic response to a famous criticism of Quine's. Others follow from issues of simplicity in the current biolinguistics program. An unexpected similarity with behaviorist practices is also uncovered. I then argue that managable and useful steps can be taken in this area.
Sensory Substitution is Substitution
Authors: Martin Jean‐Rémy , Le Corre François
Published: April 2015

Sensory substitution devices (SSDs) make use of one substituting modality (e.g. touch) to get access to environmental information normally accessed through another modality (e.g. vision). Based on behavioural and neuroimaging data, some authors have claimed that using a vision‐substituting device results in visual perception. Reviewing these data, we contend that this claim is untenable. We argue (i) that the kind of information processed by a SSD is metamodal, so that it can be accessed through any sensory modality and (ii) that the phenomenology associated with the use of a SSD is best described in terms of spatial phenomenology, only.
Aspergillus nidulans flippase DnfA is cargo of the endocytic collar and plays complementary roles in growth and phosphatidylserine asymmetry with another flippase, DnfB
Authors: Schultzhaus Zachary , Yan Huijuan , Shaw Brian D.
Published: April 2015

Endocytosis and exocytosis are strictly segregated at the ends of hyphal cells of filamentous fungi, with a collar of endocytic activity encircling the growing cell tip, which elongates through directed membrane fusion. It has been proposed that this separation supports an endocytic recycling pathway that maintains polar localization of proteins at the growing apex. In a search for proteins in the filamentous fungus Aspergillus nidulans that possess an NPFxD motif, which signals for endocytosis, a Type 4 P‐Type ATPase was identified and named DnfA. Interestingly, NPFxD is at a different region of DnfA than the same motif in the Saccharomyces cerevisiae ortholog, although endocytosis is dependent on this motif for both proteins. DnfA is involved in asexual sporulation and polarized growth. Additionally, it is segregated within the Spitzenkörper from another Type 4 P‐type ATPase, DnfB. Next, the phosphatidylserine marker GFP::Lact‐C2 was expressed in growing hyphae, which revealed that this phospholipid is enriched on the cytosolic face of secretory vesicles. This distribution is affected by deleting either dnfA or dnfB. These findings provide evidence for the spatial and temporal segregation of Type4‐ATPases in filamentous fungi, and the asymmetric distribution of phosphatidylserine to the Spitzenkörper in A. nidulans.
A conserved proline residue in Dothideomycete Avr4 effector proteins is required to trigger a Cf‐4‐dependent hypersensitive response
Authors: Mesarich Carl H. , Stergiopoulos Ioannis , Beenen Henriek G. , Cordovez Viviane , Guo Yanan , Karimi Jashni Mansoor , Bradshaw Rosie E. , de Wit Pierre J. G. M.
Published: April 2015

CfAvr4, a chitin‐binding effector protein produced by the Dothideomycete tomato pathogen Cladosporium fulvum, protects the cell wall of this fungus against hydrolysis by secreted host chitinases during infection. However, in the presence of the Cf‐4 immune receptor of tomato, CfAvr4 triggers a hypersensitive response (HR), which renders the pathogen avirulent. Recently, several orthologues of CfAvr4 have been identified from phylogenetically closely related species of Dothideomycete fungi. Of these, DsAvr4 from Dothistroma septosporum also triggers a Cf‐4‐dependent HR, but CaAvr4 and CbAvr4 from Cercospora apii and Cercospora beticola, respectively, do not. All, however, bind chitin. To identify the region(s) and specific amino acid residue(s) of CfAvr4 and DsAvr4 required to trigger a Cf‐4‐dependent HR, chimeric and mutant proteins, in which specific protein regions or single amino acid residues, respectively, were exchanged between CfAvr4 and CaAvr4 or DsAvr4 and CbAvr4, were tested for their ability to trigger an HR in Nicotiana benthamiana plants transgenic for the Cf‐4 immune receptor gene. Based on this approach, a single region common to CfAvr4 and DsAvr4 was determined to carry a conserved proline residue necessary for the elicitation of this HR. In support of this result, a Cf‐4‐dependent HR was triggered by mutant CaAvr4 and CbAvr4 proteins carrying an arginine‐to‐proline substitution at this position. This study provides the first step in deciphering how Avr4 orthologues from different Dothideomycete fungi trigger a Cf‐4‐dependent HR.
Does every transcript originate from a gene?
Authors: Raabe Carsten A. , Brosius Jürgen
Published: April 2015

Outdated gene definitions favored regions corresponding to mature messenger RNAs, in particular, the open reading frame. In eukaryotes, the intergenic space was widely regarded nonfunctional and devoid of RNA transcription. Original concepts were based on the assumption that RNA expression was restricted to known protein‐coding genes and a few so‐called structural RNA genes, such as ribosomal RNAs or transfer RNAs. With the discovery of introns and, more recently, sensitive techniques for monitoring genome‐wide transcription, this view had to be substantially modified. Tiling microarrays and RNA deep sequencing revealed myriads of transcripts, which cover almost entire genomes. The tremendous complexity of non‐protein‐coding RNA transcription has to be integrated into novel gene definitions. Despite an ever‐growing list of functional RNAs, questions concerning the mass of identified transcripts are under dispute. Here, we examined genome‐wide transcription from various angles, including evolutionary considerations, and suggest, in analogy to novel alternative splice variants that do not persist, that the vast majority of transcripts represent raw material for potential, albeit rare, exaptation events.
Asthma and allergy in children with and without prior measles, mumps, and rubella vaccination
Authors: Timmermann Clara Amalie Gade , Osuna Christa Elyse , Steuerwald Ulrike , Weihe Pál , Poulsen Lars K. , Grandjean Philippe
Published: April 2015

Background

The existing literature on the association between measles vaccination and subsequent risk of allergic disease is inconclusive. The aim of this study was, therefore, to determine whether measles, mumps, and rubella (MMR) vaccination administered in early childhood was associated with asthma and allergic diseases at ages 5, 7 and 13 yrs in a birth cohort.

Methods

In the Faroe Islands, 640 children were followed from birth. Follow‐up examinations at ages 5, 7 and 13 yrs included a physical examination and a maternal questionnaire about the child's health. At age 7, total and grass‐specific IgE was quantified in the child's serum, and at age 13, the children underwent skin prick tests (SPT). The child's vaccination card was reviewed at examinations.

Results

At age 5, 533 of 555 children had been vaccinated for MMR. After confounder adjustment, we found early life MMR vaccination to be associated with a two‐third reduction in the odds of asthma (OR: 0.33, 95% CI: 0.12; 0.90) and hypersensitivity/allergy (OR: 0.32, 95% CI: 0.11; 0.88) at age 5, and the substantially decreased odds of asthma were replicated at age 13 (OR: 0.22, 95% CI: 0.08; 0.56). At age 7, serum total IgE was reduced by 62.8% (CI 95%: −84.3%; −11.9%) in the vaccinated children. MMR vaccination was not significantly associated with allergic rhinoconjuctivitis symptoms, eczema, or SPT reactions at age 13.

Conclusions

MMR vaccination early in life may have a protective effect against allergy at least up to age 7 and against asthma through age 13 yrs.
Toward predicting metastatic progression of melanoma based on gene expression data
Authors: Li Yuanyuan , Krahn Juno M. , Flake Gordon P. , Umbach David M. , Li Leping
Published: April 2015

Primary and metastatic melanoma tumors share the same cell origin, making it challenging to identify genomic biomarkers that can differentiate them. Primary tumors themselves can be heterogeneous, reflecting ongoing genomic changes as they progress toward metastasizing. We developed a computational method to explore this heterogeneity and to predict metastatic progression of the primary tumors. We applied our method separately to gene expression and to microRNA (miRNA) expression data from ~450 primary and metastatic skin cutaneous melanoma (SKCM) samples from the Cancer Genome Atlas (TCGA). Metastatic progression scores from RNA‐seq data were significantly associated with clinical staging of patients’ lymph nodes, whereas scores from miRNA‐seq data were significantly associated with Clark's level. The loss of expression of many characteristic epithelial lineage genes in primary SKCM tumor samples was highly correlated with predicted progression scores. We suggest that those genes/miRNAs might serve as putative biomarkers for SKCM metastatic progression.
Carrots or Sticks? Improving Social and Environmental Compliance at Suppliers Through Incentives and Penalties
Authors: Porteous Angharad H. , Rammohan Sonali V. , Lee Hau L.
Published: April 2015

Firms are increasingly looking to eradicate social and environmental non‐compliances at their suppliers in response to increasing regulations, consumer demand, potential for supply chain disruptions, and to improve their social, environmental, and economic supply chain performance. This study develops a model of the relationship between the buyer's supplier incentives and penalties for the supplier's social and environmental compliance, and the outcomes in terms of reduction in supplier social and environmental violations as well as the buyer's own operating costs. This model is tested empirically through analysis of a dataset of opinion‐based survey responses from practitioners at 334 companies across 17 industries. The analysis finds specific penalties and incentives that are positively associated with reduced supplier violations and reduced buyer operating costs. In particular, offering suppliers incentives of increased business and training for improving social and environmental performance is strongly associated with a reduction in both violations and operating costs.
Reducing Hospital Readmissions by Integrating Empirical Prediction with Resource Optimization
Authors: Helm Jonathan E. , Alaeddini Adel , Stauffer Jon M. , Bretthauer Kurt M. , Skolarus Ted A.
Published: April 2015

Hospital readmissions present an increasingly important challenge for health‐care organizations. Readmissions are expensive and often unnecessary, putting patients at risk and costing $15 billion annually in the United States alone. Currently, 17% of Medicare patients are readmitted to a hospital within 30 days of initial discharge with readmissions typically being more expensive than the original visit to the hospital. Recent legislation penalizes organizations with a high readmission rate. The medical literature conjectures that many readmissions can be avoided or mitigated by post‐discharge monitoring. To develop a good monitoring plan it is critical to anticipate the timing of a potential readmission and to effectively monitor the patient for readmission causing conditions based on that knowledge. This research develops new methods to empirically generate an individualized estimate of the time to readmission density function and then uses this density to optimize a post‐discharge monitoring schedule and staffing plan to support monitoring needs. Our approach integrates classical prediction models with machine learning and transfer learning to develop an empirical density that is personalized to each patient. We then transform an intractable monitoring plan optimization with stochastic discharges and health state evolution based on delay‐time models into a weakly coupled network flow model with tractable subproblems after applying a new pruning method that leverages the problem structure. Using this multi‐methodologic approach on two large inpatient datasets, we show that optimal readmission prediction and monitoring plans can identify and mitigate 40–70% of readmissions before they generate an emergency readmission.
Material Offshoring: Alternate Measures
Authors: Baldwin John R. , Gu Wulong , Sydor Aaron , Yan Beiling
Published: April 2015

Industry measures of offshoring of material inputs are often generated using the proportionality assumption applied to aggregate import data—that the import share of each commodity used in the production process for a particular industry is similar to the import share of a commodity for the total economy. This note compares estimates of offshoring for the Canadian manufacturing sector derived using this assumption to four alternatives: two measures that use direct measures of firm‐based imports, and two hybrid measures that use both input and import information. These indirect measures are compared to survey estimates that directly assess import intensity in the production process in an effort to evaluate which indirect method yields more reasonable offshoring measures.
Police and Thieves in the Stadium: Measuring the (Multiple) Effects of Football Matches on Crime
Authors: Marie Olivier
Published: April 2015

Large sporting events affect criminal behaviour via three channels: fan concentration, self-incapacitation and police displacement. I exploit information on football matches for London teams linked to detailed recorded crime data at the area level to estimate these effects empirically. I find that only property crime increases in the communities hosting matches but not violent offences. There is a negative away game attendance effect on crime which is due to voluntary incapacitation of potential offenders attending a match. Police displacement during home games increases property crime by 7 percentage points for every extra 10000 supporters in areas that are left underprotected.