bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonidine modulates the activity of the subthalamic‐supplementary motor loop: evidence from a pharmacological study combining deep brain stimulation and electroencephalography recordings in Parkinsonian patients
Authors: Spay Charlotte , Albares Marion , Lio Guillaume , Thobois Stephane , Broussolle Emmanuel , Lau Brian , Ballanger Benedicte , Boulinguez Philippe
Published: April 2018

Clonidine is an anti‐hypertensive medication which acts as an alpha‐adrenergic receptor agonist. As the noradrenergic system is likely to support cognitive functions including attention and executive control, other clinical uses of clonidine have recently gained popularity for the treatment of neuropsychiatric disorders like attention‐deficit hyperactivity disorder or Tourette syndrome, but the mechanism of action is still unclear. Here, we test the hypothesis that the noradrenergic system regulates the activity of subthalamo‐motor cortical loops, and that this influence can be modulated by clonidine. We used pharmacological manipulation of clonidine in a placebo‐controlled study in combination with subthalamic nucleus‐deep brain stimulation (STN‐DBS) in 16 Parkinson's disease patients performing a reaction time task requiring to refrain from reacting (proactive inhibition). We recorded electroencephalographical activity of the whole cortex, and applied spectral analyses directly at the source level after advanced blind source separation. We found only one cortical source localized to the supplementary motor area (SMA) that supported an interaction of pharmacological and subthalamic stimulation. Under placebo, STN‐DBS reduced proactive alpha power in the SMA, a marker of local inhibitory activity. This effect was associated with the speeding‐up of movement initiation. Clonidine substantially increased proactive alpha power from the SMA source, and canceled out the benefits of STN‐DBS on movement initiation. These results provide the first direct neural evidence in humans that the tonic inhibitory activity of the subthalamocortical loops underlying the control of movement initiation is coupled to the noradrenergic system, and that this activity can be targeted by pharmacological agents acting on alpha‐adrenergic receptors.

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Erythropoietin regulates the expression of dimeric form of acetylcholinesterase during differentiation of erythroblast
Authors: Xu Miranda L. , Luk Wilson K. W. , Bi Cathy W. C. , Liu Etta Y. L. , Wu Kevin Q. Y. , Yao Ping , Dong Tina T. X. , Tsim Karl W. K.
Published: April 2018

Acetylcholinesterase (AChE; EC 3.1.1.7) is known to hydrolyze acetylcholine at cholinergic synapses. In mammalian erythrocyte, AChE exists as a dimer (G2) and is proposed to play role in erythropoiesis. To reveal the regulation of AChE during differentiation of erythroblast, erythroblast‐like cells (TF‐1) were induced to differentiate by application of erythropoietin (EPO). The expression of AChE was increased in parallel to the stages of differentiation. Application of EPO in cultured TF‐1 cells induced transcriptional activity of ACHE gene, as well as its protein product. This EPO‐induced event was in parallel with erythrocytic proteins, for example, α‐ and β‐globins. The EPO‐induced AChE expression was mediated by phosphorylations of Akt and GATA‐1; because the application of Akt kinase inhibitor blocked the gene activation. Erythroid transcription factor also known as GATA‐1, a downstream transcription factor of EPO signaling, was proposed here to account for regulation of AChE in TF‐1 cell. A binding sequence of GATA‐1 was identified in ACHE gene promoter, which was further confirmed by chromatin immunoprecipitation (ChIP) assay. Over‐expression of GATA‐1 in TF‐1 cultures induced AChE expression, as well as activity of ACHE promoter tagged with luciferase gene (pAChE‐Luc). The deletion of GATA‐1 sequence on the ACHE promoter, pAChEΔGATA‐1‐Luc, reduced the promoter activity during erythroblastic differentiation. On the contrary, the knock‐down of AChE in TF‐1 cultures could lead to a reduction in EPO‐induced expression of erythrocytic proteins. These findings indicated specific regulation of AChE during maturation of erythroblast, which provided an insight into elucidating possible mechanisms in regulating erythropoiesis.

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Hearing vulnerability after noise exposure in a mouse model of reactive oxygen species overproduction
Authors: Morioka Shigefumi , Sakaguchi Hirofumi , Yamaguchi Taro , Ninoyu Yuzuru , Mohri Hiroaki , Nakamura Takashi , Hisa Yasuo , Ogita Kiyokazu , Saito Naoaki , Ueyama Takehiko
Published: April 2018

Previous studies have convincingly argued that reactive oxygen species (ROS) contribute to the development of several major types of sensorineural hearing loss, such as noise‐induced hearing loss (NIHL), drug‐induced hearing loss, and age‐related hearing loss. However, the underlying molecular mechanisms induced by ROS in these pathologies remain unclear. To resolve this issue, we established an in vivo model of ROS overproduction by generating a transgenic (TG) mouse line expressing the human NADPH oxidase 4 (NOX4, NOX4‐TG mice), which is a constitutively active ROS‐producing enzyme that does not require stimulation or an activator. Overproduction of ROS was detected at the cochlea of the inner ear in NOX4‐TG mice, but they showed normal hearing function under baseline conditions. However, they demonstrated hearing function vulnerability, especially at high‐frequency sounds, upon exposure to intense noise, which was accompanied by loss of cochlear outer hair cells (OHCs). The vulnerability to loss of hearing function and OHCs was rescued by treatment with the antioxidant Tempol. Additionally, we found increased protein levels of the heat‐shock protein 47 (HSP47) in models using HEK293 cells, including H2O2 treatment and cells with stable and transient expression of NOX4. Furthermore, the up‐regulated levels of Hsp47 were observed in both the cochlea and heart of NOX4‐TG mice. Thus, antioxidant therapy is a promising approach for the treatment of NIHL. Hsp47 may be an endogenous antioxidant factor, compensating for the chronic ROS overexposure in vivo, and counteracting ROS‐related hearing loss.

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Can Taxes Shape an Industry? Evidence from the Implementation of the “Amazon Tax”
Authors: BAUGH BRIAN , BEN‐DAVID ITZHAK , PARK HOONSUK
Published: April 2018

For years, online retailers have maintained a price advantage over brick‐and‐mortar retailers by not collecting sales tax at the time of sale. Recently, several states have required that online retailer Amazon collect sales tax during checkout. Using transaction‐level data, we document that households living in these states reduced their Amazon purchases by 9.4% following the implementation of the sales tax laws, implying elasticities of –1.2 to –1.4. The effect is stronger for large purchases, where purchases declined by 29.1%, corresponding to an elasticity of –3.9. Studying competitors in the electronics field, we find some evidence of substitution toward competing retailers.
Transmission of “Candidatus Phytoplasma pruni”‐related strain associated with broccoli stunt by four species of leafhoppers
Authors: Kreyci Patrícia Fabretti , Eckstein Bárbara , Lopes João Roberto Spotti , Ferreira Jacson , Bedendo Ivan Paulo
Published: April 2018

A disease known as broccoli stunt, associated with “Candidatus Phytoplasma pruni”‐related strain, has been responsible by significant economic losses in crops grown in the State of São Paulo, Brazil. Previous investigations evidenced some species of leafhoppers observed in broccoli fields as potential vectors of the phytoplasma. In this study, the six species more frequently found in broccoli crops were collected to confirm that evidence. Group of five insects of each species were confined per broccoli seedling for an inoculation access period (IAP) of 48 hr. After the IAP, each group was tested for detection of phytoplasma. Evaluation of plants was performed 60 days after inoculation based on the presence of phytoplasma in their tissues. When transmission was positive, genomic fragments corresponding to 16S rDNA were sequenced both for the infected plants and its respective group of insects. The results revealed that the species Agallia albidula, Agalliana sticticollis, Atanus nitidus and Balcluta hebe were able to transmit phytoplasma to broccoli seedlings. Based on the estimates of transmission probability by single insects (P), the highest transmission rate was observed for A. nitidus (24.2%) and the lowest for B. hebe (1.9%). The sequencing of 16S rDNA revealed complete similarity between the sequences of the phytoplasma transmitted to broccoli test plants and the sequences of the phytoplasma found in the field‐collected leafhoppers. These findings support the inclusion of those species as vectors of phytoplasmas belonging to 16SrIII group in broccolis, providing additional information to improve management of this important disease of endemic occurrence.
Nonnative Gracilaria vermiculophylla tetrasporophytes are more difficult to debranch and are less nutritious than gametophytes
Authors: Lees Lauren E. , Krueger‐Hadfield Stacy A. , Clark Andrew J. , Duermit Elizabeth A. , Sotka Erik E. , Murren Courtney J.
Published: April 2018

Theory predicts that the maintenance of haplodiplontic life cycles requires ecological differences between the haploid gametophytes and diploid sporophytes, yet evidence of such differences remain scarce. The haplodiplontic red seaweed Gracilaria vermiculophylla has invaded the temperate estuaries of the Northern Hemisphere, where it commonly modifies detrital and trophic pathways. In native populations, abundant hard substratum enables spore settlement, and gametophyte:tetrasporophyte ratios are ~40:60. In contrast, many non‐native populations persist in soft‐sediment habitats without abundant hard substratum, and can be 90%–100% tetrasporophytic. To test for ecologically relevant phenotypic differences, we measured thallus morphology, protein content, organic content, “debranching resistance” (i.e., tensile force required to remove a branch from its main axis node), and material properties between male gametophytes, female gametophytes, and tetrasporophytes from a single, nonnative site in Charleston Harbor, South Carolina, USA in 2015 and 2016. Thallus length and surface area to volume ratio differed between years, but were not significantly different between ploidies. Tetrasporophytes had lower protein content than gametophytes, suggesting the latter may be more attractive to consumers. More force was required to pull a branch from the main axis of tetrasporophytes relative to gametophytes. A difference in debranching resistance may help to maintain tetrasporophyte thallus durability relative to gametophytes, providing a potential advantage in free‐floating populations. These data may shed light on the invasion ecology of an important ecosystem engineer, and may advance our understanding of life cycle evolution and the maintenance of life cycle diversity.
The Keys to Unlocking Public Payments Data
Authors: Rahal Charles
Published: April 2018

We mechanize some of the richest yet significantly under‐utilized data resources within developed, ‘Open Data' economies. We show how it is possible to scrape, parse, clean and merge tens of thousands of disaggregated public payments datasets in an attempt to bridge the methodological gap between newly available data from the administrative sphere and applications in empirical social science research. We outline techniques to unambiguously link records to various freely available institutional registers. In particular, we offer guidance on overcoming the substantial challenges of heterogeneous provision and administrative recording errors in the absence of Uniform Resource Identifiers, namely in the form of an approximate, domain‐specific ‘record‐linkage' type matching algorithm. As an illuminating example, we construct a cleaned database of 24,581,192 local government payments subject to the Local Transparency Codes which total £169.87bn in value. We overcome various challenges in a detailed examination of the procurement of services by local government from the voluntary sector: an important contemporary issue due to the rise of the ‘Big Society’ political ideology of the early 21st century. Finally, we motivate future work in this area and discuss potential international applications and practical advancements.
Foraging and feeding ecology of Platanista: an integrative review
Authors: Kelkar Nachiket , Dey Subhasis , Deshpande Kadambari , Choudhary Sunil Kumar , Dey Sushant , Morisaka Tadamichi
Published: April 2018

Limited visual perception in aquatic environments has driven the evolution of diverse sensory modalities in aquatic mammals. Dolphins largely use echolocation for prey capture in the face of limited visual and olfactory cues. Multiple foraging modes exist, although an understanding of how sensory systems are adapted to environmental and prey characteristics is limited. This is especially true for animals with extreme sensory specialisation, such as South Asian river dolphins of the genus Platanista. This taxon is effectively blind and retains plesiomorphic traits from its once‐diverse ancestors. Distributed in murky rivers of the Indus‐Ganga‐Brahmaputra basins, it is thought to use mainly echolocation for feeding on fish and shrimp.

We hypothesised that foraging modes used by Platanista differ according to prey position in the water column (at the river surface, mid‐column, and bottom) and are mediated by ecomorphology, acoustics, prey characteristics, and habitat features.

To test this, we combined a detailed review of the literature (anatomy–physiology–morphology studies, observations in captivity) with preliminary field observations and acoustics studies to investigate foraging mode selection.

Platanista displays peculiar foraging and feeding behaviours, including side swimming, rotational feeding, and grasp‐suction feeding. Feeding is restricted to small prey with low body depth. At the river surface and bottom, echolocation‐based foraging may not be efficient due to acoustic reflection or reverberation effects.

Platanista uses echolocation clicks to scan and detect prey at distances of about 20 m across the river mid‐column, possibly switching to passive listening at the surface, and electroreception at the bottom, to maximise prey capture rate and feeding success.

Platanista is remarkable for its ability to persist in some of the most intensively used and abused river basins of the world. Using echolocation, electroreception, and passive listening might reduce overall foraging costs and contribute to the adaptability of the taxon.
Shrub range expansion alters diversity and distribution of soil fungal communities across an alpine elevation gradient
Authors: Collins Courtney G. , Stajich Jason E. , Weber Sören E. , Pombubpa Nuttapon , Diez Jeffrey M.
Published: April 2018

Global climate and land use change are altering plant and soil microbial communities worldwide, particularly in arctic and alpine biomes where warming is accelerated. The widespread expansion of woody shrubs into historically herbaceous alpine plant zones is likely to interact with climate to affect soil microbial community structure and function; however, our understanding of alpine soil ecology remains limited. This study aimed to (i) determine whether the diversity and community composition of soil fungi vary across elevation gradients and to (ii) assess the impact of woody shrub expansion on these patterns. In the White Mountains of California, sagebrush (Artemisia rothrockii) shrubs have been expanding upwards into alpine areas since 1960. In this study, we combined observational field data with a manipulative shrub removal experiment along an elevation transect of alpine shrub expansion. We utilized next‐generation sequencing of the ITS1 region for fungi and joint distribution modelling to tease apart effects of the environment and intracommunity interactions on soil fungi. We found that soil fungal diversity declines and community composition changes with increasing elevation. Both abiotic factors (primarily soil moisture and soil organic C) and woody sagebrush range expansion had significant effects on these patterns. However, fungal diversity and relative abundance had high spatial variation, overwhelming the predictive power of vegetation type, elevation and abiotic soil conditions at the landscape scale. Finally, we observed positive and negative associations among fungal taxa which may be important in structuring community responses to global change.
Meta‐analysis of chromosome‐scale crossover rate variation in eukaryotes and its significance to evolutionary genomics
Authors: Haenel Quiterie , Laurentino Telma G. , Roesti Marius , Berner Daniel
Published: April 2018

Understanding the distribution of crossovers along chromosomes is crucial to evolutionary genomics because the crossover rate determines how strongly a genome region is influenced by natural selection on linked sites. Nevertheless, generalities in the chromosome‐scale distribution of crossovers have not been investigated formally. We fill this gap by synthesizing joint information on genetic and physical maps across 62 animal, plant and fungal species. Our quantitative analysis reveals a strong and taxonomically widespread reduction of the crossover rate in the centre of chromosomes relative to their peripheries. We demonstrate that this pattern is poorly explained by the position of the centromere, but find that the magnitude of the relative reduction in the crossover rate in chromosome centres increases with chromosome length. That is, long chromosomes often display a dramatically low crossover rate in their centre, whereas short chromosomes exhibit a relatively homogeneous crossover rate. This observation is compatible with a model in which crossover is initiated from the chromosome tips, an idea with preliminary support from mechanistic investigations of meiotic recombination. Consequently, we show that organisms achieve a higher genome‐wide crossover rate by evolving smaller chromosomes. Summarizing theory and providing empirical examples, we finally highlight that taxonomically widespread and systematic heterogeneity in crossover rate along chromosomes generates predictable broad‐scale trends in genetic diversity and population differentiation by modifying the impact of natural selection among regions within a genome. We conclude by emphasizing that chromosome‐scale heterogeneity in crossover rate should urgently be incorporated into analytical tools in evolutionary genomics, and in the interpretation of resulting patterns.
The hetZ gene indirectly regulates heterocyst development at the level of pattern formation in Anabaena sp. strain PCC 7120
Authors: Videau Patrick , Rivers Orion S. , Tom Sasa K. , Oshiro Reid T. , Ushijima Blake , Swenson Vaille A. , Philmus Benjamin , Gaylor Michael O. , Cozy Loralyn M.
Published: April 2018

Multicellular development requires the careful orchestration of gene expression to correctly create and position specialized cells. In the filamentous cyanobacterium Anabaena sp. strain PCC 7120, nitrogen‐fixing heterocysts are differentiated from vegetative cells in a reproducibly periodic and physiologically relevant pattern. While many genetic factors required for heterocyst development have been identified, the role of HetZ has remained unclear. Here, we present evidence to clarify the requirement of hetZ for heterocyst production and support a model where HetZ functions in the patterning stage of differentiation. We show that a clean, nonpolar deletion of hetZ fails to express the developmental genes hetR, patS, hetP and hetZ correctly and fails to produce heterocysts. Complementation and overexpression of hetZ in a hetP mutant revealed that hetZ was incapable of bypassing hetP, suggesting that it acts upstream of hetP. Complementation and overexpression of hetZ in a hetR mutant, however, demonstrated bypass of hetR, suggesting that it acts downstream of hetR and is capable of bypassing the need for hetR for differentiation irrespective of nitrogen status. Finally, protein–protein interactions were observed between HetZ and HetR, Alr2902 and HetZ itself. Collectively, this work suggests a regulatory role for HetZ in the patterning phase of cellular differentiation in Anabaena.
Pediatric ganglioglioma with an H3 K27M mutation arising from the cervical spinal cord
Authors: Okuda Tomohiro , Hata Nobuhiro , Suzuki Satoshi O , Yoshimoto Koji , Arimura Koichi , Amemiya Takeo , Akagi Yojiro , Kuga Daisuke , Oba Utako , Koga Yuhki , Ohga Shouichi , Iwaki Toru , Iihara Koji
Published: April 2018

The 2016 edition of the World Health Organization Classification of Tumors of the Central Nervous System introduced “diffuse midline glioma H3 K27M mutant” as a new diagnostic entity. These tumors predominately affect pediatric patients and arise from midline structures such as the brainstem, thalamus and spinal cord. Here, we report a rare patient with spinal ganglioglioma carrying an H3 K27M mutation. A 10‐year‐old boy presented with an intramedullary tumor in the cervical spinal cord. The lesion was partially removed and histologically diagnosed as ganglioglioma. After the remnant tumor grew within 3 months after surgery, the patient underwent radiotherapy. Genetic analyses revealed an H3F3A K27M mutation but no other genetic alterations such as IDH and BRAF mutations. This case may point to pathological heterogeneity in gliomas with H3 K27M mutations.
Economic evaluations of system‐based obesity interventions – the case for a new approach
Authors: Sonntag D. , Sweeney R. , Litaker D. , Moodie M.
Published: April 2018

System‐based interventions are of increasing interest as they seek to modify environments (e.g. socio‐cultural system, transport system or policy system) that promote development of conditions such as obesity and its related risk factors. In our commentary, we draw attention to features of the system‐based approach that may explain the relative absence of economic evaluations of the cost‐effectiveness of these interventions, needed to guide decision‐making on which to deploy. We present and discuss potentially applicable methods and alternative approaches based on our experiences in two major system‐based interventions currently underway (in Melbourne, Australia and Gaggenau, Germany) that begin to fill this gap. We feel the issues and potential solutions outlined in this commentary are important for a broad range of stakeholders (e.g. clinicians, interventionalists, policy makers) to consider as they seek to address the issue of obesity.
Rule A
Authors: Turner P. Roger , Capes Justin
Published: April 2018

Rule A: if it's metaphysically necessary that p, we may validly infer that no one is even partly morally responsible for the fact that p. Our principal aim in this article is to highlight the importance of this rule and to respond to two recent challenges to it. We argue that rule A is more important to contemporary theories of moral responsibility than has previously been recognized. We then consider two recent challenges to the rule and argue that neither challenge successfully undermines the rule's initial appeal.
Treatment of recurrent focal segmental glomerulosclerosis post‐kidney transplantation in Australian and New Zealand children: A retrospective cohort study
Authors: Francis Anna , Didsbury Madeleine , McCarthy Hugh , Kara Tonya
Published: April 2018

Disease recurrence affects around a third of renal transplants for children with FSGS and is associated with poor graft outcomes. Unfortunately, there are no large trials guiding treatment for recurrent FSGS. We aimed to describe current therapies and treatment response for recurrent FSGS in 4 centres in Australia and New Zealand. Data were collected on children (age <18 years) with recurrent FSGS (1990‐2015). We reviewed patient charts to obtain clinical information. Ethics approval was obtained from the relevant boards. Complete records were available on 24 patients (62% female, 54% Caucasian). Median time to first recurrence was 4 days (IQR 2‐5 days). There were 14 separate treatment regimens, involving an average of 2 agents. The most common therapies were plasma exchange (20/24 patients, 83%), cyclosporin (15/24, 63%), and methylprednisolone (9/24, 38%). Full remission was achieved in 15 (63%), partial remission in 2 (8%), and no remission in 7 (29%) patients. Of the patients with no remission, 5 lost their graft to recurrent disease and 1 to concurrent acute vascular rejection. The plethora of different treatment regimens reflects the poor evidence guiding management for recurrent FSGS. More research is needed to improve outcomes.
A falls case summary: Application of the public health nursing intervention wheel
Authors: Leahy‐Warren Patricia , Day Mary Rose , Philpott Lloyd , Glavin Kari , Gjevjon Edith Roth , Steffenak Anne Kjersti Myhrene , Nordhagen Live S. , Egge Hilde , Healy Elizabeth , Mulcahy Helen
Published: April 2018

Background

The Public Health Intervention Wheel (PHIW) is a population‐based practice model that encompasses three levels of practice (community, systems, and individual/family) and 17 public health interventions. Each intervention and practice level contributes to improving population health. Public health nurses (PHNs) provide care at the three levels of practice. Prevention of falls is a public health issue and the majority of falls happen at home. Therefore, prevention and management of falls in the community could benefit from a public health systems approach by PHNs underpinned by the PHIW.

Case Presentation

A hypothetical case is presented of a 78‐year‐old gentleman who had a fall which resulted in a fractured right acetabulum and surgery before being discharged home.

Methods

The aim of this paper was to use a case summary to illustrate PHN practice in the context of the PHIW as applied to falls management and prevention. This paper focuses on fall incidence and PHN response in Ireland and Norway. The PHIW is described and relevant interventions from the PHIW are applied to PHN practice in managing the case.

Conclusions

The PHIW model provides insight into the potential scope of public health nursing in falls, articulating PHN practice in the community.
Hemodialysis: A model for extreme physiology in a vulnerable patient population
Authors: Kooman Jeroen P. , Katzarski Krassimir , van der Sande Frank M. , Leunissen Karel M. , Kotanko Peter
Published: April 2018

Hemodialysis (HD) is a lifesaving treatment for patients with end‐stage renal disease, which is very efficient in the correction of abnormalities of the internal environment. However, this efficiency also induces significant hemodynamic, thermal, and respiratory stressors. These have parallels with the extreme physiologic demands which are normally mainly experienced by healthy subjects under adverse environmental conditions, with the difference that they must be endured by a vulnerable patient population. Hemodynamic stress induced by ultrafiltration leads to a decline in circulating blood volume, which may result in intradialytic hypotension (IDH) and changes in tissue perfusion, which may have long‐term consequences for the function of vital organs such as the brain and the heart. Pronounced declines in central venous oxygen saturation have been observed during routine HD, which are related to the circulatory stress imposed upon the patient. Apart from patient‐related factors, thermal stress induced by HD may lead to skin vasodilation, counteracting the normal hemodynamic response to hypovolemia, which has important pathophysiologic correlates in heat syncope. Lastly, respiratory stress is reflected by prolonged arterial hypoxemia during HD, which is both related to patient‐related factors, but may also be partly because of the treatment itself, especially during the first 30‐60 minutes. Whereas hypoxemia during HD is related to increased mortality, its role in the reduced tissue oxygen delivery during HD should be further defined. Treatment modifications, such as cool or temperature‐controlled HD, may reduce circulatory and thermal stress, which also may translate into a reduced risk of long‐term cardiac or cerebral damage. However, as circulatory stress is mainly time‐dependent, prolonged, or more dialysis treatment may reduce the homeostatic burden on the patient.
The Magic of the Personal Touch: Field Experimental Evidence on Money and Appreciation as Gifts*
Authors: Bradler Christiane , Neckermann Susanne
Published: April 2018

In this paper, we use two field experiments in professional settings to explore the effort levels of individuals in response to gifts. We extend the literature by looking at non‐financial gifts that signal worker appreciation and gifts that combine financial and non‐financial elements with or without a personal touch. We find that while money and appreciation are individually effective, these only work well together when they are combined with a personal touch. This suggests that responses to gifts are sensitive to the presentation of the gift as well as to interpersonal elements; these are factors that have so far been largely ignored in the literature but are easy to incorporate into existing principal–agent models.
Smoothed Isotonic Estimators of a Monotone Baseline Hazard in the Cox Model
Authors: Lopuhaä Hendrik P. , Musta Eni
Published: April 2018

We consider the smoothed maximum likelihood estimator and the smoothed Grenander‐type estimator for a monotone baseline hazard rateλ0in the Cox model. We analyze their asymptotic behaviour and show that they are asymptotically normal at ratenm/(2m+1), when λ0ism≥2 times continuously differentiable, and that both estimators are asymptotically equivalent. Finally, we present numerical results on pointwise confidence intervals that illustrate the comparable behaviour of the two methods.
An Optimal Semiparametric Method for Two‐group Classification
Authors: Baek Seungchul , Komori Osamu , Ma Yanyuan
Published: April 2018

In the classical discriminant analysis, when two multivariate normal distributions with equal variance–covariance matrices are assumed for two groups, the classical linear discriminant function is optimal with respect to maximizing the standardized difference between the means of two groups. However, for a typical case‐control study, the distributional assumption for the case group often needs to be relaxed in practice. Komori et al. (Generalized t‐statistic for two‐group classification. Biometrics 2015, 71: 404–416) proposed the generalized t‐statistic to obtain a linear discriminant function, which allows for heterogeneity of case group. Their procedure has an optimality property in the class of consideration. We perform a further study of the problem and show that additional improvement is achievable. The approach we propose does not require a parametric distributional assumption on the case group. We further show that the new estimator is efficient, in that no further improvement is possible to construct the linear discriminant function more efficiently. We conduct simulation studies and real data examples to illustrate the finite sample performance and the gain that it produces in comparison with existing methods.
The analysis of left truncated bivariate data using frailty models
Authors: Wang Antai , Chandra Krishnendu , Jia Xieyang
Published: April 2018

In this paper, we study the properties of frailty models for bivariate data under fixed left truncation. It turns out that the distribution of completely observable pairs is also a member of the Archimedean copula family. We propose a new estimation strategy to analyze this type of data using the corresponding Kendall distribution. A general goodness‐of‐fit test procedure is then developed for selecting the best model. Our strategies are generalization of the methodologies proposed for left truncated data. We demonstrate our new approaches using simulations and an illustrative example and end our paper with some discussion.
“Embodying” dirty work: A review of the literature
Authors: Simpson Ruth , Simpson Alexander
Published: April 2018

This article reviews the growing literature on dirty work, i.e., work that is seen as disgusting or degrading and argues for a more “embodied” understanding of such work. It points to a tendency in the literature to focus on the nature of the task or role and on social and moral dimensions of the work at the expense of its material and embodied aspects. The latter are discussed through three, interrelated themes: “embodied suitability” whereby forms of dirty work are seen as suitable for some “working bodies” and not for others; “staining” which is presented as both a material and a symbolic process; and the role of work practices in both supporting and undermining ideological constructions around the work. The article concludes by arguing for a more comprehensive approach which includes both the material and the symbolic into accounts of such work.
Language comprehension as a multi‐label classification problem
Authors: Sering Konstantin , Milin Petar , Baayen R. Harald
Published: April 2018

The initial stage of language comprehension is a multilabel classification problem. Listeners or readers, presented with an utterance, need to discriminate between the intended words and the tens of thousands of other words they know. We propose to address this problem by pairing two networks. The first network is independently learned with the Rescorla Wagner model. The second network is based on the first network and learned with the rule of Widrow and Hoff. The first network has to recover from sublexical input features the meanings encoded in the language signal, resulting in a vector of activations over the lexicon. The second network takes this vector as input and further reduces uncertainty about the intended message. Classification performance for a lexicon with 52,000 entries is good. The model also correctly predicts several aspects of human language comprehension. By rejecting the traditional linguistic assumption that language is a (de)compositional system, and by instead espousing a discriminative approach, a more parsimonious yet highly effective functional characterization of the initial stage of language comprehension is obtained.
Sexual assault
Authors: Long Lisa , Butler Bernadette
Published: April 2018

Key content

Sexual assault is common, with one in five women aged 16–59 years having experienced sexual violence.

The choices for women regarding reporting sexual assault and referral to a sexual assault referral centre should be widely known in obstetrics and gynaecology.

Healthcare professionals should offer basic first aid, emergency contraception and screening/prophylaxis for sexually transmitted infections including HIV.

This article outlines the role of the forensic medical examination and future long‐term needs of women who have experienced sexual assault.

The basic laws regarding sexual assault are discussed.

Learning objectives

To understand the prevalence of sexual assault and its impact on women's health.

To understand the basic appropriate management of those reporting sexual assault and the different options available to women.

To be able to document findings and take early evidence.

Ethical issues

Healthcare professionals are often frightened of the disclosure. They need to be supportive and non‐judgemental.

Careful documentation of history and findings are important in view of possible legal proceedings.

Sharing of information with other professionals may need to be considered without having the client's consent to protect vulnerable adults, adolescents and general public.
Latent therapeutic demand model for the immunoglobulin replacement therapy of primary immune deficiency disorders in the USA
Authors: Stonebraker J. S. , Hajjar J. , Orange J. S.
Published: April 2018

Background and Objectives

Our research aim is to model latent therapeutic demand (LTD) for the immunoglobulin replacement therapy (IgGRT) of primary immune deficiency disorders (PIDDs) in the USA. Given the high level of variability of IgGRT use and major differences among American and European practices in the management of patients with PIDDs, we develop a USA‐specific LTD model for common variable immune deficiency (CVID), hyper IGM syndrome, severe combined immune deficiency, Wiskott–Aldrich syndrome and X‐linked agammaglobulinemia (XLA).

Methods and Materials

We use decision analysis methods to model the underlying IgGRT demand for PIDDs by assessing USA‐specific epidemiology and treatment. Data for the epidemiology and treatment variables were obtained from the medical literature, USIDNET and Immune Deficiency Foundation. The uncertainty surrounding the variables was modelled using probability distributions and evaluated using Monte Carlo simulation.

Results

The mean treatment dose from USIDNET and European Society for Immunodeficiencies (ESID) was significantly different for treating CVID, and the number of annual infusions from USIDNET and ESID was significantly different for treating CVID and XLA. The mean and standard deviation of LTD for all PIDDs is 105·1 ± 88·5 g per 1000 population, with CVID contributing the most to LTD.

Conclusion

Estimating country‐specific LTD is important to ensure an adequate supply of IgGRT and an optimal treatment for patients with PIDDs and for improving national healthcare policymaking and production planning.
Prolonged prenatal hypoxia selectively disrupts collecting duct patterning and postnatal function in male mouse offspring
Authors: Walton Sarah L , Singh Reetu R , Little Melissa H , Bowles Josephine , Li Joan , Moritz Karen M
Published: April 2018

Key points

In the present study, we investigated whether hypoxia during late pregnancy impairs kidney development in mouse offspring, and also whether this has long‐lasting consequences affecting kidney function in adulthood.

Hypoxia disrupted growth of the kidney, particularly the collecting duct network, in juvenile male offspring. By mid‐late adulthood, these mice developed early signs of kidney disease, notably a compromised response to water deprivation.

Female offspring showed no obvious signs of impaired kidney development and did not develop kidney disease, suggesting an underlying protection mechanism from the hypoxia insult.

These results help us better understand the long‐lasting impact of gestational hypoxia on kidney development and the increased risk of chronic kidney disease.

Prenatal hypoxia is a common perturbation to arise during pregnancy, and can lead to adverse health outcomes in later life. The long‐lasting impact of prenatal hypoxia on postnatal kidney development and maturation of the renal tubules, particularly the collecting duct system, is relatively unknown. In the present study, we used a model of moderate chronic maternal hypoxia throughout late gestation (12% O2 exposure from embryonic day 14.5 until birth). Histological analyses revealed marked changes in the tubular architecture of male hypoxia‐exposed neonates as early as postnatal day 7, with disrupted medullary development and altered expression of Ctnnb1 and Crabp2 (encoding a retinoic acid binding protein). Kidneys of the RARElacZ line offspring exposed to hypoxia showed reduced β‐galactosidase activity, indicating reduced retinoic acid‐directed transcriptional activation. Wild‐type male mice exposed to hypoxia had an early decline in urine concentrating capacity, evident at 4 months of age. At 12 months of age, hypoxia‐exposed male mice displayed a compromised response to a water deprivation challenge, which was was correlated with an altered cellular composition of the collecting duct and diminished expression of aquaporin 2. There were no differences in the tubular structures or urine concentrating capacity between the control and hypoxia‐exposed female offspring at any age. The findings of the present study suggest that prenatal hypoxia selectively disrupts collecting duct patterning through altered Wnt/β‐catenin and retinoic acid signalling and this results in impaired function in male mouse offspring in later life.
A distributed subband valley fusion (DSVF) method for low frequency broadband target localization
Authors: Wang Lu , Yang Yixin , Liu Xionghou
Published: April 2018

A distributed subband valley fusion method is proposed in this paper for target localization for a multi-array fusion system. Instead of employing two-step processing like the traditional bearings-only target localization (BOTL) methods, the target location estimate is directly obtained from the intersection of the estimated bearing line of each array, which is automatically produced after applying a subband valley energy detection process to the reciprocal of the steered response power over predefined grid points. Bearing information at all frequencies and ranges are used to generate the bearing line and the intersection structure, leading to higher localization accuracy in comparison with the BOTL methods. In multiple-target situations, the data association problem is solved by distinguishing true targets from the ghost ones from the power and the number of bearing lines at the corresponding intersection grid point. The method is subsequently tested by the SWellEx-96 shallow water experiment data set. Simulation and experimental results demonstrate the localization accuracy of the proposed method.
An Ecological Exploration of Facilitators to Participation in a Mosque-Based Physical Activity Program for South Asian Muslim Women
Authors: Abdulwasi Munira , Bhardwaj Meena , Nakamura Yuka , Zawi Maha , Price Jennifer , Harvey Paula , Banerjee Ananya Tina
Published: April 2018

Background: This descriptive qualitative study informed by an ecological framework explored factors influencing South Asian Muslim women’s decisions to participate in a mosque-based physical activity intervention. Methods: Individual, face-to-face, semistructured interviews were conducted in English, Hindi, or Urdu with 12 South Asian Muslim women at their home or mosque in Ontario, Canada. All interviews were audio-recorded, transcribed verbatim and managed, sorted, and analyzed for themes through a process of descriptive analysis. Results: The participants described as follows: (1) intrapersonal facilitators, which included their feelings, beliefs, and motivations to continue with this intervention; (2) interpersonal facilitators detailing the support that they had received from others during the intervention; and (3) environmental facilitators, which highlighted convenience and access to physical activity opportunities in a local community setting. Conclusion: This intervention displayed how South Asian Muslim women were motivated to continue with the mosque-based physical activity intervention due to interpersonal, intrapersonal, and environmental facilitators. The findings can be used to increase further understanding of how mosques may provide culturally and religiously sensitive contexts for physical activity interventions for South Asian Muslim women.
Imidacloprid Decreases Honey Bee Survival Rates but Does Not Affect the Gut Microbiome
Authors: Raymann Kasie , Motta Erick V. S. , Girard Catherine , Riddington Ian M. , Dinser Jordan A. , Moran Nancy A.
Published: April 2018

Accumulating evidence suggests that pesticides have played a role in the increased rate of honey bee colony loss. One of the most commonly used pesticides in the United States is the neonicotinoid imidacloprid. Although the primary mode of action of imidacloprid is on the insect nervous system, it has also been shown to cause changes in insects' digestive physiology and alter the microbiota of
Drosophila melanogaster
larvae. The honey bee gut microbiome plays a major role in bee health. Although many studies have shown that imidacloprid affects honey bee behavior, its impact on the microbiome has not been fully elucidated. Here, we investigated the impact of imidacloprid on the gut microbiome composition, survivorship, and susceptibility to pathogens of honey bees. Consistent with other studies, we show that imidacloprid exposure results in an elevated mortality of honey bees in the hive and increases the susceptibility to infection by pathogens. However, we did not find evidence that imidacloprid affects the gut bacterial community of honey bees. Our
in vitro
experiments demonstrated that honey bee gut bacteria can grow in the presence of imidacloprid, and we found some evidence that imidacloprid can be metabolized in the bee gut environment. However, none of the individual bee gut bacterial species tested could metabolize imidacloprid, suggesting that the observed metabolism of imidacloprid within
in vitro
bee gut cultures is not caused by the gut bacteria. Overall, our results indicate that imidacloprid causes increased mortality in honey bees, but this mortality does not appear to be linked to the microbiome.

IMPORTANCE
Growing evidence suggests that the extensive use of pesticides has played a large role in the increased rate of honey bee colony loss. Despite extensive research on the effects of imidacloprid on honey bees, it is still unknown whether it impacts the community structure of the gut microbiome. Here, we investigated the impact of imidacloprid on the gut microbiome composition, survivorship, and susceptibility to pathogens of honey bees. We found that the exposure to imidacloprid resulted in an elevated mortality of honey bees and increased the susceptibility to infection by opportunistic pathogens. However, we did not find evidence that imidacloprid affects the gut microbiome of honey bees. We found some evidence that imidacloprid can be metabolized in the bee gut environment
in vitro
, but because it is quickly eliminated from the bee, it is unlikely that this metabolism occurs in nature. Thus, imidacloprid causes increased mortality in honey bees, but this does not appear to be linked to the microbiome.
Resistance of Bacteria to Biocides
Authors: Maillard Jean-Yves
Published: April 2018

Biocides and formulated biocides are used worldwide for an increasing number of applications despite tightening regulations in Europe and in the United States. One concern is that such intense usage of biocides could lead to increased bacterial resistance to a product and cross-resistance to unrelated antimicrobials including chemotherapeutic antibiotics. Evidence to justify such a concern comes mostly from the use of health care-relevant bacterial isolates, although the number of studies of the resistance characteristics of veterinary isolates to biocides have increased the past few years. One problem remains the definition of “resistance” and how to measure resistance to a biocide. This has yet to be addressed globally, although the measurement of resistance is becoming more pressing, with regulators both in Europe and in the United States demanding that manufacturers provide evidence that their biocidal products will not impact on bacterial resistance. Alongside
in vitro
evidence of potential antimicrobial cross-resistance following biocide exposure, our understanding of the mechanisms of bacterial resistance and, more recently, our understanding of the effect of biocides to induce a mechanism(s) of resistance in bacteria has improved. This article aims to provide an understanding of the development of antimicrobial resistance in bacteria following a biocide exposure. The sections provide evidence of the occurrence of bacterial resistance and its mechanisms of action and debate how to measure bacterial resistance to biocides. Examples pertinent to the veterinary field are used where appropriate.