bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain region‐specific neuromedin U signalling regulates alcohol‐related behaviours and food intake in rodents
Authors: Vallöf Daniel , Kalafateli Aimilia Lydia , Jerlhag Elisabet
Published: May 2019

Albeit neuromedin U (NMU) attenuates alcohol‐mediated behaviours, its mechanisms of action are poorly defined. Providing that the behavioural effects of alcohol are processed within the nucleus accumbens (NAc) shell, anterior ventral tegmental area (aVTA), and laterodorsal tegmental area (LDTg), we assessed the involvement of NMU signalling in the aforementioned areas on alcohol‐mediated behaviours in rodents. We further examined the expression of NMU and NMU receptor 2 (NMUR2) in NAc and the dorsal striatum of high compared with low alcohol‐consuming rats, as this area is of importance in the maintenance of alcohol use disorder (AUD). Finally, we investigated the involvement of NAc shell, aVTA and LDTg in the consumption of chow and palatable peanut butter, to expand the link between NMU and reward‐related behaviours. We demonstrated here, that NMU into the NAc shell, but not aVTA or LDTg, blocked the ability of acute alcohol to cause locomotor stimulation and to induce memory retrieval of alcohol reward, as well as reduced peanut butter in mice. In addition, NMU into NAc shell decreased alcohol intake in rats. On a molecular level, we found increased NMU and decreased NMUR2 expression in the dorsal striatum in high compared with low alcohol‐consuming rats. Both aVTA and LDTg, rather than NAc shell, were identified as novel sites of action for NMU's anorexigenic properties in mice based on NMU's ability to selectively reduce chow intake when injected to these areas. Collectively, these data indicate that NMU signalling in different brain areas selectively modulates different behaviours.
Double‐lumen tracheal tubes and bougies: a bench study to investigate factors that influence the risk of shearing
Authors: Luther D. G. P. , Robertson H. F. , Suchett‐Kaye I. , Birch A. , Molyneux M.
Published: May 2019

Tracheal intubation with a double‐lumen tube can be more challenging than with a single‐lumen tube. A bougie can be used to facilitate intubation. Case reports have described fragment shearing from bougies when they are removed from the tube after intubation. These fragments have the potential to cause harm. It has even been suggested that bougies and double‐lumen tubes should not be used together. We conducted a benchtop trial to investigate factors that influence the risk of shearing. We investigated three brands of double‐lumen tube (each in three sizes and both lateralities) and four brands of bougie. We simulated one intubation and 29 further insertions/removals of bougie with every bougie–double‐lumen tube combination. We inspected the inside of the tube for evidence of shearing after first, tenth and thirtieth removals. We found that brand of bougie, brand of double‐lumen tube and size of double‐lumen tube (but not its laterality) all influenced the degree of shearing. Certain bougie–double‐lumen tube combinations produced a particularly high degree of shearing, so these should be avoided.
Comparing the sterility and visibility of surgical marking pens available in Australia
Authors: O'Bryan Edward , Pollock Michaela , Joseph Samuel
Published: May 2019

Background

Surgical site marking is an important safety procedure prior to surgery. Visibility of pen marks is affected by surgical wash which increases the risk of wrong‐site surgery. Additionally, multiple patient contact with a single pen is a potential source of bacterial transmission. In this study we compare pens commonly used for surgical marking in Australia.

Methods

We conducted an unblinded, prospective cohort study comparing 12 marking pens. Six volunteers' thighs were marked with each pen. Standardized photographs were taken before and after wash with four prep solutions. Ink visibility was analysed using grayscale images, comparing the pen mark tone before and after wash. The pen tips were swabbed for culture.

Results

Red tinted 2% chlorhexidine gluconate (w/v) with 70% isopropyl alcohol (v/v) was shown to reduce pen mark visibility significantly more than the other solutions used. The Pentel N50 permanent marker and Aspen WriteSite Plus were least affected by wash. No pen tip cultured any bacteria.

Conclusions

When marking the correct site for surgery, we recommend the use of either the Pentel N50 permanent marker or Aspen Writesite Plus pen. A 2‐min interval between patient contact limits bacterial transmission.
Longitudinal outcomes in pediatric‐ and adult‐onset bipolar patients compared to healthy and schizophrenia controls
Authors: Frahm Laursen Mathilde , Valentin Jan B. , Licht Rasmus W. , Correll Christoph U. , Nielsen René E.
Published: May 2019

Objectives

Comparing outcomes of bipolar disorder (BD) with schizophrenia (SCZ) and psychiatrically healthy controls (PHC), contrasting pediatric‐onset with adult‐onset disorders.

Methods

A nationwide cohort study, including patients with an incident diagnosis of BD or SCZ registered in the Danish National Patient Registry and corresponding PHCs. Outcomes were (a) duration of hospitalization, (b) psychiatric admissions, (c) psychiatric outpatient contacts, (d) bone‐fracture‐related healthcare contacts, (e) self‐harm‐related healthcare contacts (including suicide and non‐suicidal self‐injuries), and (f) criminal charges. Incidence rate ratios (IRRs), adjusted for age at first psychiatric contact, substance abuse and parental psychiatric illness, were calculated, comparing pediatric‐onset BD (5‐17 years) and adult‐onset BD (18‐39 years) with age‐ and sex‐matched SCZ patients and PHC.

Results

Pediatric‐onset BD (n = 349) performed better than 1:1‐matched pediatric‐onset SCZ (n = 349) on all six outcomes (IRR = 0.30 for self‐harm‐related contacts (P < 0.001) to IRR = 0.86 for criminal charges (P = 0.05). Similar, but less pronounced results were observed comparing 1:1‐matched adult‐onset BD (n = 5515) with adult‐onset SCZ (n = 5515) IRR = 0.58 for psychiatric outpatient contact (P < 0.001) to IRR = 0.93 for criminal charges (P < 0.001), except for more bone‐fracture‐related contacts in adult‐onset BD (IRR = 1.13, P < 0.01). Comparing pediatric‐onset BD (n = 365) to 1:3‐matched PHC (n = 1095), only self‐harm‐related contacts differed significantly (IRR = 2.80, P < 0.001). Conversely, comparing adult‐onset BD (n = 6005) with 1:3‐matched PHC (n = 18 015), self‐harm‐related contacts (IRR = 16.68, P < 0.001), bone fractures (IRR = 1.74, P < 0.001), and criminal charges (IRR = 2.03, P < 0.001) were more common in BD.

Conclusion

BD was associated with poorer outcomes than PHC, but better outcomes than SCZ. Furthermore, outcomes were more favorable in pediatric‐onset BD when indirectly contrasted to adult‐onset BD.
Effectiveness of management zoning designed for flagship species in protecting sympatric species
Authors: Shen Xiaoli , Li Sheng , McShea William J. , Wang Dajun , Yu Jianping , Shi Xiaogang , Dong Wei , Mi Xiangcheng , Ma Keping
Published: May 2019

Flagship species have been used widely as umbrella species (i.e., species with large home range whose protection often provides protection for sympatric species) in the management of China's nature reserves. This conflation of flagship and umbrella species is best represented by the giant panda (Ailuropoda melanoleuca) and other large, endangered mammals designated as conservation targets in site selection and planning of reserves. Few empirical studies have tested the effectiveness of flagship species as surrogates for a broader range of sympatric species. Using extensive camera‐trap data, we examined the effectiveness of management zones designated to protect flagship (target) species in conserving sympatric species in 4 wildlife reserves (Gutianshan, Changqing, Laohegou, and Wolong). We tested whether the progression from peripheral to core zones was associated with an increasing habitat association for both target and sympatric species. The distribution patterns of the study species across the zones in each reserve indicated a disparity between management zones and the species’ habitat requirements. Management zone was included in the final model for all target species, and most of them had higher occurrence in core zones relative to less‐protected zones, but zone was not a predictor for most of the sympatric species. When management zone was associated with the occurrence of sympatric species, threatened species generally had higher detections in core zones, whereas common species had higher detections outside of the core zone. Our results suggested that reserve planning based on flagship species does not adequately protect sympatric species due to their specialized habitat requirements. We recommend re‐examining the effectiveness of management zoning and urge a multispecies and reserve‐wide monitoring plan to improve protection of China's wildlife.
Unpacking the ‘Emergent Farmer’ Concept in Agrarian Reform: Evidence from Livestock Farmers in South Africa
Authors: Gwiriri Lovemore C. , Bennett James , Mapiye Cletos , Burbi Sara
Published: May 2019

South Africa has historically perpetuated a dual system of freehold commercial and communal subsistence farming. To bridge these extremes, agrarian reform policies have encouraged the creation of a class of ‘emergent’, commercially oriented farmers. However, these policies consider ‘emergent’ farmers as a homogeneous group of land reform beneficiaries, with limited appreciation of the class differences between them, and do little to support the rise of a ‘middle’ group of producers able to bridge that gap. This article uses a case study of livestock farmers in Eastern Cape Province to critique the ‘emergent farmer’ concept. The authors identify three broad categories of farmers within the emergent livestock sector: a large group who, despite having accessed private farms, remain effectively subsistence farmers; a smaller group of small/medium‐scale commercial producers who have communal farming origins and most closely approximate to ‘emergent’ farmers; and an elite group of large‐scale, fully commercialized farmers, whose emergence has been facilitated primarily by access to capital and a desire to invest in alternative business ventures. On this basis the authors suggest that current agrarian reform policies need considerable refocusing if they are to effectively facilitate the emergence of a ‘middle’ group of smallholder commercial farmers from communal systems.
Laboratory diagnosis of heparin‐induced thrombocytopenia
Authors: Warkentin Theodore E.
Published: May 2019

Heparin‐induced thrombocytopenia (HIT) is a clinical‐pathological disorder; thus, laboratory testing for the pathogenic platelet‐activating antiplatelet factor 4 (PF4)/heparin antibodies is central for diagnosis. The “iceberg” model summarizes the inter‐relationship between platelet activation assays and PF4‐dependent immunoassays, with platelet‐activating antibodies comprising a subset of anti‐PF4/heparin antibodies. The platelet serotonin‐release assay (SRA), performed by reference laboratories, has high sensitivity and specificity for HIT (~95% each), and is especially suited for detecting highly pathogenic HIT sera containing both heparin‐dependent and heparin‐independent platelet‐activating antibodies; this latter subgroup of antibodies explains “autoimmune HIT” disorders (delayed‐onset, persisting, spontaneous, heparin “flush,” fondaparinux‐associated). Recently, SRA‐negative HIT has become recognized, in which serum from some HIT patients contains subthreshold levels of platelet‐activating antibodies (by SRA) that become detectable using a PF4‐enhanced platelet activation assay. Unusual immunologic features of HIT include early antibody detectability (at onset of platelet count fall) and antibody transience (seroreversion). Widely available PF4‐dependent enzyme immunoassays (EIAs) have high sensitivity but poor specificity for HIT, although specificity is enhanced with IgG‐specific EIAs and strong positive results; unfortunately, EIA results are usually not available in real time. Automated rapid immunoassays, such as the chemiluminescence immunoassay (CLIA) and latex immunoturbidimetric assay (LIA), facilitate real‐time laboratory diagnosis. Recently available likelihood ratio (LR) data for positive (LR+) and negative (LR−) test results allow clinicians to adjust their pretest probabilities for HIT, using Bayesian analysis, into real‐time posttest probabilities that are dramatically increased (test positive) or decreased (test negative). Moreover, (semi‐)quantitative CLIA‐ and LIA‐positive results (weak, moderate, strong positive) can further refine the posttest probability of HIT.
Sensitive and accurate identification of PNH clones based on ICCS/ESCCA PNH Consensus Guidelines—A summary
Authors: Illingworth Andrea J. , Marinov Iuri , Sutherland D. Robert
Published: May 2019

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disorder resulting from the somatic mutation of the X‐linked phosphatidyl‐inositol glycan complementation Class A (PIG‐A) gene. Depending on the severity of the mutation in the PIG‐A gene, there is a partial or absolute inability to make glycosylphosphatidyl‐inositol (GPI)‐anchored proteins including complement‐defense structures such as CD55 and CD59 on RBCs and WBCs. Flow cytometric detection of PNH clones has become the gold standard and has played an increasingly important role in the diagnosis, monitoring, and clinical management of patients with PNH. Recently, a 4‐part set of Consensus Guidelines have been published by flow experts in the field to address the key assay‐specific considerations for the identification of PNH clones in RBC and WBC, how to report such data and a full validation document for the assays described. Below, we have summarized the most significant aspects of this International effort.
Flow cytometry data analysis: Recent tools and algorithms
Authors: Montante Sebastiano , Brinkman Ryan R.
Published: May 2019

Flow cytometry (FCM) allows scientists to rapidly quantify up to 50 parameters for millions of cells per sample. The bottleneck in the application of the technology is data analysis, and the high number of parameters measured by the current generation of instruments requires the use of advanced computational algorithms to make full use of their capabilities. This review summarizes the main steps ofFCMdata analysis, focusing on the use of the most recent bioinformatic tools developed for an R‐based programming environment. In particular, for each stage of the data analysis, libraries and packages currently available are listed, and a brief description of their functioning is included.
Recognition of child physical abuse by a group of Brazilian primary care health professionals
Authors: Silva‐Oliveira Fernando , Andrade Carlos Inácio , Guimarães Mariana Oliveira , Ferreira Raquel Conceição , Ferreira Efigênia Ferreira , Zarzar Patrícia Maria
Published: May 2019

Background

Child maltreatment is a complex social and public health problem.

Aim

To evaluate the frequency of the recognition by Brazilian health professionals in primary care of child physical abuse (CPA) and associated factors.

Design

A representative cross‐sectional study was conducted with dentists, nurses, family physicians, and pediatricians who participated in the network of the Family Health Strategy in the city of Belo Horizonte, Brazil. Data collection involved in the administration of a questionnaire validated for use in Brazil. Data were collected from 181 dentists, 235 nurses, 203 family physicians, and 96 pediatricians.

Results

Among the 715 health professionals, 499 (69.8%) had some type of postgraduate degree and 414 (57.9%) recognized suspected or proved cases of CPA. The recognition was associated with occupation, as pediatricians recognized 14.11‐fold [OR = 14.11 (95% CI: 3.73 to 53.43)] more cases of CPA compared with dentists. The recognition was also associated with a longer period of time working in the city [OR = 2.79 (95% CI: 1.24 to 6.29)].

Conclusion

The recognition of cases was positively associated with the longer working time in the municipal network and with pediatricians. The dentist was the category that was least associated with the recognition of CPA.
Longitudinal examination of pancreatic β‐cell function in Japanese individuals
Authors: Fujikawa Rumi , Ito Chikako , Kira Sakurako , Misumi Munechika
Published: May 2019

Aims/Introduction

We carried out a retrospective, longitudinal analysis of β‐cell function between a diabetes mellitus group, including those that progressed to diabetes mellitus during the follow‐up period, and a diabetic type with glycated hemoglobin (HbA1c) <6.5 group, including those that progressed to a diabetic type during the follow‐up period. β‐Cell function was assessed using homeostasis model of assessment of β‐cell function.

Materials and Methods

The relationship between the duration of diabetes mellitus or the diabetic type and pancreatic β‐cell function was compared between the diabetes mellitus group (1,817) and diabetic type with HbA1c <6.5 group (1,843) using results from an oral glucose tolerance test. Linear mixed effects models were used to analyze repeated measurements of oral glucose tolerance tests.

Results

The slope of the regression line of β‐cell function for the duration of the diabetes mellitus group was −2.2%/year before the diagnosis. The slope differed after the diagnosis, and the difference was 1.3. The slope of the diabetic type group was −1.2%/year, and no significant difference was observed in the slope before and after the diagnosis. β‐Cell function at the onset was 54.3% in the diabetic type group and 40.6% in the diabetes mellitus group, and the slope of the regression line was significantly higher in the diabetes mellitus group. We divided the diabetes mellitus and diabetic type with HbA1c <6.5 groups into obese and non‐obese participants. β‐Cell function declined more with obesity.

Conclusions

Subsequent declines in β‐cell function were faster in the diabetes mellitus group than that in the diabetic type with HbA1c <6.5 group, and increased with obesity.
Synthetic testosterone derivatives modulate rat P2X2 and P2X4 receptor channel gating
Authors: Sivcev Sonja , Slavikova Barbora , Rupert Marian , Ivetic Milorad , Nekardova Michaela , Kudova Eva , Zemkova Hana
Published: May 2019

P2X receptors (P2XRs) are ATP‐gated cationic channels that are allosterically modulated by numerous compounds, including steroids and neurosteroids. These compounds may both inhibit and potentiate the activity of P2XRs, but sex steroids such as 17β‐estradiol or progesterone are reported to be inactive. Here, we tested a hypothesis that testosterone, another sex hormone, modulates activity of P2XRs. We examined actions of native testosterone and a series of testosterone derivatives on the gating of recombinant P2X2R, P2X4R and P2X7R and native channels expressed in pituitary cells and hypothalamic neurons. The 17β‐ester derivatives of testosterone rapidly and positively modulate the 1 µM ATP‐evoked currents in P2X2R‐ and P2X4R‐expressing cells, but not agonist‐evoked currents in P2X7R‐expressing cells. In general, most of the tested testosterone derivatives are more potent modulators than endogenous testosterone. The comparison of chemical structures and whole‐cell recordings revealed that their interactions with P2XRs depend on the lipophilicity and length of the alkyl chain at position C‐17. Pre‐treatment with testosterone butyrate or valerate increases the sensitivity of P2X2R and P2X4R to ATP by several fold, reduces the rate of P2X4R desensitization, accelerates resensitization, and enhances ethidium uptake by P2X4R. Native channels are also potentiated by testosterone derivatives, while endogenously expressed GABA receptors type A are inhibited. The effect of ivermectin, a P2X4R‐specific allosteric modulator, on deactivation is antagonized by testosterone derivatives in a concentration‐dependent manner. Together, our results provide evidence for potentiation of particular subtypes of P2XRs by testosterone derivatives and suggest a potential role of ivermectin binding site for steroid‐induced modulation.

Open Science Badges

This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

image
Callosal septa express guidance cues and are paramedian guideposts for human corpus callosum development
Authors: Culjat Marko , Milošević Nataša Jovanov
Published: May 2019

The early development and growth of the corpus callosum are supported by several midline transient structures in mammals that include callosal septa (CS), which are present only in the second half of gestation in humans. Here we provide new data that support the guidance role of CS in corpus callosum development, derived from the analysis of 46 postmortem fetal brains, ranging in age from 16 to 40 post conception weeks (PCW). Using immunohistochemical methods, we show the expression pattern of guidance cues ephrinA4 and neogenin, extracellular protein fibronectin, as well as non‐activated microglia in the CS. We found that the dynamic changes in expression of guidance cues, cellular and extracellular matrix constituents in the CS correlate well with the growth course of the corpus callosum at midsagittal level. The CS reach and maintain their developmental maximum between 20 and 26 PCW and can be visualized as hypointense structures in the ventral callosal portion with ex vivo (in vitro) T2‐weighted 3T magnetic resonance imaging (MRI). The maximum of septal development overlaps with an increase in the callosal midsagittal area, whereas the slow, gradual resolution of CS coincides with a plateau of midsagittal callosal growth. The recognition of CS existence in human fetal brain and the ability to visualize them by ex vivoMRI attributes a potential diagnostic value to these transient structures, as advancement in imaging technologies will likely also enable in vivoMRI visualization of the CS in the near future.
How do stomata respond to water status?
Authors: Buckley Thomas N.
Published: May 2019

Stomatal responses to humidity, soil moisture and other factors that influence plant water status are critical drivers of photosynthesis, productivity, water yield, ecohydrology and climate forcing, yet we still lack a thorough mechanistic understanding of these responses. Here I review historical and recent advances in stomatal water relations. Clear evidence now implicates a metabolically mediated response to leaf water status (‘hydroactive feedback’) in stomatal responses to evaporative demand and soil drought, possibly involving abscisic acid production in leaves. Other hypothetical mechanisms involving vapor and heat transport within leaves may contribute to humidity, light and temperature responses, but require further theoretical clarification and experimental validation. Variation and dynamics in hydraulic conductance, particularly within leaves, may contribute to water status responses. Continuing research to fully resolve mechanisms of stomatal responses to water status should focus on several areas: validating and quantifying the mechanism of leaf‐based hydroactive feedback, identifying where in leaves water status is actively sensed, clarifying the role of leaf vapor and energy transport in humidity and temperature responses, and verifying foundational but minimally replicated results of stomatal hydromechanics across species. Clarity on these matters promises to deliver modelers with a tractable and reliable mechanistic model of stomatal responses to water status.
Virtual simulation training: Imaged experience of dementia
Authors: Slater Paul , Hasson Felicity , Gillen Patricia , Gallen Anne , Parlour Randal
Published: May 2019

Background and objectives

The need to provide an empathic response to the care of people with dementia has long been advocated. Virtual reality‐based programmes continue to gain momentum across health sectors, becoming an innovative tool that provides staff with the opportunity to experience a dementia‐like experience within a relatively short time frame. The purpose of this study is to explore the impact of an interactive training experience on moral, emotive, behavioural and cognitive elements of empathy.

Research design and methods

A qualitative exploratory design was adopted employing purposive sampling to identify participants, aged over 18 years, who participated in the Virtual Dementia Tour (VDT®) programme. Interviews were conducted over a two‐month period, and qualitative thematic analysis was used to analyse the data.

Results

The four components (moral, emotive, behavioural and cognitive) of empathy were reflected in findings. Overall the interactive training programme was perceived as useful, and emotionally, it provided an opportunity to “imagine what it is to live with dementia,” enabling a cognitive, moral and behavioural reflection to occur, enhancing the empathic state.

Discussion

In this study, the VDT® provides a different way of learning, with participants reporting the emergence of an empathic response. Results suggest that the emotional response laid the foundations to the behavioural or cognitive (objective and subjective) reaction which was underpinned by a moral reaction.

Implications for practice

Virtual reality programmes are one step in the process for healthcare professionals caring empathetically for people with dementia; however, further research is required.
Policy dismantling at EU level: Reaching the limits of ‘an ever‐closer ecological union’?
Authors: Gravey Viviane , Jordan Andrew J.
Published: May 2019

Having explained their adoption, analysts are now trying to understand how EU environmental policies have subsequently evolved over time. In 2003, David Vogel famously speculated that having overtaken the US in the environmental race to the top, EU policies would also eventually succumb to policy gridlock, that is, neither expanding nor dismantling. Empirical research has since confirmed that EU policy expansion is in decline, but less is known about why dismantling has also been very limited. This article breaks new ground by reconfiguring dismantling—a concept developed for national policy systems—to explain the various dismantling strategies deployed at EU level (1992 to 2016). It finds that the absence of significant dismantling is due both to the symbolic nature of early dismantling attempts and the failure of more recent attempts to build coalitions that overcome institutional obstacles to policy change in the EU.
Copy number of the X‐linked genes TLR7 and CD40L influences innate and adaptive immune responses
Authors: Sarmiento Luis , Svensson Johan , Barchetta Ilaria , Giwercman Aleksander , Cilio Corrado M.
Published: May 2019

The number of the X chromosome–linked genes has been previously suggested to influence immune responses and the development of autoimmune diseases. In the present study, we aimed at evaluating the level of expression of CD40L (an X‐linked gene involved in adaptive immunity) and TLR7 (an X‐linked gene involved in innate immunity) in a variety of different karyotypes. Those included males, females and patients with X chromosome aneuploidy. Healthy females (46, XX; n = 10) and healthy males (46, XY; n = 10) were compared to females with Turner syndrome (TS) (45, X; n = 11) and males with Klinefelter syndrome (KS) (47, XXY; n = 5). Stimulation of peripheral blood mononuclear cells (PBMCs) with PMA and ionomycin resulted in higher percentage of CD3 + CD40L+ T cells (P < 0.001) and higher level expression of CD40L in T cell (P < 0.001) in female and KS patients compared with male and TS patients. TLR7‐mediated IFN‐alpha production by HLADR + CD3− CD19− cells was significantly upregulated in healthy women compared with healthy males, TS and KS patients (P < 0.001). TLR7 agonist‐stimulated PBMCs from healthy females and KS patients expressed significantly higher levels of TLR7 mRNA than those from male and TS patients (P < 0.05). The increased expression of the X‐linked genes TLR7 and CD40L in healthy females and KS patients suggests that the presence of two X chromosomes plays a major role in enhancing both innate and adaptive immune responses. These results may contribute to the explanation of sex‐based differences in immune biology and the sex bias in predisposition to autoimmune diseases.
Quality wars in the North
Authors: Choi Yoonho , Choi Eun Kwan
Published: May 2019

This paper investigates two stylised facts about quality wars between Northern firms and a Southern copycat firm in the North. First, due to low wage, a foreign or Southern copycat firm may enter the market of a developed economy inhabited by a high‐quality firm and a low‐quality domestic copycat. When the products of the high‐quality firm and the foreign copycat are vertically differentiated, the foreign copycat firm may choose an intermediate quality between the quality levels of domestic high‐ and low‐quality firms. In the second scenario where the products of the high‐quality firm and the foreign copycat are horizontally differentiated, the quality of the foreign copycat may surpass that of the domestic high‐quality firm. As the wage gap between the developed and developing countries widens, the foreign copycat is more likely to survive in the markets of developed economies.
Gata3 is required for the functional maturation of inner hair cells and their innervation in the mouse cochlea
Authors: Bardhan Tanaya , Jeng Jing‐Yi , Waldmann Marco , Ceriani Federico , Johnson Stuart L. , Olt Jennifer , Rüttiger Lukas , Marcotti Walter , Holley Matthew C.
Published: May 2019

Key points

The physiological maturation of auditory hair cells and their innervation requires precise temporal and spatial control of cell differentiation.

The transcription factor gata3 is essential for the earliest stages of auditory system development and for survival and synaptogenesis in auditory sensory afferent neurons.

We show that during postnatal development in the mouse inner ear gata3 is required for the biophysical maturation, growth and innervation of inner hair cells; in contrast, it is required only for the survival of outer hair cells.

Loss of gata3 in inner hair cells causes progressive hearing loss and accounts for at least some of the deafness associated with the human hypoparathyroidism, deafness and renal anomaly (HDR) syndrome.

The results show that gata3 is critical for later stages of mammalian auditory system development where it plays distinct, complementary roles in the coordinated maturation of sensory hair cells and their innervation.

The zinc finger transcription factor gata3 regulates inner ear development from the formation of the embryonic otic placode. Throughout development, gata3 is expressed dynamically in all the major cochlear cell types. Its role in afferent formation is well established but its possible involvement in hair cell maturation remains unknown. Here, we find that in heterozygous gata3 null mice (gata3+/−) outer hair cells (OHCs) differentiate normally but their numbers are significantly lower. In contrast, inner hair cells (IHCs) survive normally but they fail to acquire adult basolateral membrane currents, retain pre‐hearing current and efferent innervation profiles and have fewer ribbon synapses. Targeted deletion of gata3 driven by otoferlin‐cre recombinase (gata3fl/flotof‐cre+/−) in IHCs does not affect OHCs or the number of IHC afferent synapses but it leads to a failure in IHC maturation comparable to that observed in gata3+/− mice. Auditory brainstem responses in gata3fl/flotof‐cre+/− mice reveal progressive hearing loss that becomes profound by 6–7 months, whilst distortion product otoacoustic emissions are no different to control animals up to this age. Our results, alongside existing data, indicate that gata3 has specific, complementary functions in different cell types during inner ear development and that its continued expression in the sensory epithelium orchestrates critical aspects of physiological development and neural connectivity. Furthermore, our work indicates that hearing loss in human hypoparathyroidism, deafness and renal anomaly (HDR) syndrome arises from functional deficits in IHCs as well as loss of function from OHCs and both afferent and efferent neurons.
Particulate methane monooxygenase contains only mononuclear copper centers
Authors: Ross Matthew O. , MacMillan Fraser , Wang Jingzhou , Nisthal Alex , Lawton Thomas J. , Olafson Barry D. , Mayo Stephen L. , Rosenzweig Amy C. , Hoffman Brian M.
Published: May 2019

How many metals to oxidize methane?

Methane is an important fuel, but there are few direct transformations to partially oxidized products. Bacteria use metalloenzymes to catalyze methane oxidation to methanol, a reaction of industrial interest. Understanding the metal sites that enable this reaction may inspire new biomimetic catalysts. Ross
et al.
used spectroscopic measurements to assign two monocopper sites in the enzyme particulate methane monooxygenase. These results differ in part from previous proposals for the location and nuclearity of the metal sites and will prompt rethinking about how this metalloenzyme catalyzes methane oxidation.

Science
, this issue p.
566
Building upon foundations for evidence-based policy
Authors: Hahn Robert
Published: May 2019

Can government culture evolve under a promising new law?
Why coal ash and tailings dam disasters occur
Authors: Santamarina J. Carlos , Torres-Cruz Luis A. , Bachus Robert C.
Published: May 2019

Knowledge gaps and management shortcomings contribute to catastrophic dam failures
Comment on “Activation of methane to CH
3
+
: A selective industrial route to methanesulfonic acid”
Authors: Roytman Vladislav A. , Singleton Daniel A.
Published: May 2019

Díaz-Urrutia and Ott (Reports, 22 March 2019, p. 1326) report a selective conversion of methane to methanesulfonic acid that is proposed to occur by a cationic chain reaction in which CH
3
+
adds to sulfur trioxide (SO
3
) to form CH
3
–S(O)
2
O
+
. This mechanism is not plausible because of the solvent reactivity of CH
3
+
, the non-nucleophilicity of the sulfur atom of SO
3
, and the high energy of CH
3
–S(O)
2
O
+
.
Functional Characterization of a Miniature Inverted Transposable Element at the Origin of
mcr-5
Gene Acquisition in Escherichia coli
Authors: Kieffer Nicolas , Nordmann Patrice , Millemann Yves , Poirel Laurent
Published: May 2019

Plasmid-mediated colistin resistance of the mobile colistin resistance (MCR) type is a growing concern in
Enterobacteriaceae
since it has been described worldwide in humans and animals. Here, we identified a series of MCR-producing
Escherichia coli
isolates corresponding to two different clones (represented by isolates PS1 and PS8b) producing MCR-1 and MCR-5, respectively, obtained from pig fecal samples in France.
It is good to feel better, but better to feel good: whether a patient finds treatment ‘successful’ or not depends on the questions researchers ask
Authors: Roos Ewa M , Boyle Eleanor , Frobell Richard B , Lohmander L Stefan , Ingelsrud Lina Holm
Published: May 2019

Introduction

In sports physiotherapy, medicine and orthopaedic randomised controlled trials (RCT), the investigators (and readers) focus on the difference between groups in change scores from baseline to follow-up. Mean score changes are difficult to interpret (‘is an improvement of 20 units good?’), and follow-up scores may be more meaningful. We investigated how applying three different responder criteria to change and follow-up scores would affect the ‘outcome’ of RCTs. Responder criteria refers to participants’ perceptions of how the intervention affected them.

Methods

We applied three different criteria—minimal important change (MIC), patient acceptable symptom state (PASS) and treatment failure (TF)—to the aggregate Knee injury and Osteoarthritis Outcome Score (KOOS4) and the five KOOS subscales, the primary and secondary outcomes of the KANON trial (ISRCTN84752559). This trial included young active adults with an acute ACL injury and compared two treatment strategies: exercise therapy plus early reconstructive surgery, and exercise therapy plus delayed reconstructive surgery, if needed.

Results

MIC: At 2 years, more than 90% in the two treatment arms reported themselves to be minimally but importantly improved for the primary outcome KOOS4. PASS: About 50% of participants in both treatment arms reported their KOOS4follow-up scores to be satisfactory. TF: Almost 10% of participants in both treatment arms found their outcomes so unsatisfactory that they thought their treatment had failed. There were no statistically significant or meaningful differences between treatment arms using these criteria.

Conclusion

We applied change criteria as well as cross-sectional follow-up criteria to interpret trial outcomes with more clinical focus. We suggest researchers apply MIC, PASS and TF thresholds to enhance interpretation of KOOS and other patient-reported scores. The findings from this study can improve shared decision-making processes for people with an acute ACL injury.
Exploring psychiatrists’ perspectives of working with patients with dissociative seizures in the UK healthcare system as part of the CODES trial: a qualitative study
Authors: Jordan Harriet , Feehan Sarah , Perdue Iain , Murray Joanna , Goldstein Laura H
Published: May 2019

Objective

There is currently limited research exploring healthcare professionals’ (HCPs) experiences of working with patients with dissociative seizures (DS). Existing studies do not focus on the role of psychiatrists in treating this complex condition. The objective of this study was to gain an understanding of UK-based psychiatrists’ experiences of the DS patient group. Against the backdrop of a UK-wide randomised controlled trial (RCT), the focus was broadened to encompass issues arising in everyday practice with the DS patient group.

Design, participants and methods

A qualitative study using semistructured interviews was undertaken with 10 psychiatrists currently working with DS patients within the context of a large RCT investigating treatments for DS. Thematic analysis was used to identify key themes and subthemes.

Setting

The psychiatrists were working in Liaison or Neuropsychiatry services in England.

Results

The key themes identified were other HCPs’ attitudes to DS and the challenges of the DS patient group. There is a clear knowledge gap regarding DS for many HCPs and other clinical services can be reluctant to take referrals for this patient group. Important challenges posed by this patient group included avoidance (of difficult emotions and help), alexithymia and interpersonal difficulties. Difficulties with alexithymia meant DS patients could struggle to identify triggers for their seizures and to express their emotions. Interpersonal difficulties raised included difficulties in attachment with both HCPs and family members.

Conclusions

A knowledge gap for HCPs regarding DS has been identified and needs to be addressed to improve patient care. Given the complexity of the patient group and that clinicians from multiple disciplines will come into contact with DS patients, it is essential for any educational strategy to be implemented across the whole range of specialties, and to account for those already in practice as well as future trainees.

Trial registration number

ISRCTN05681227;NCT02325544; Pre-results.
Ultrasonic strain elastography for detecting abnormalities in the supraspinatus tendon: an intra- and inter-rater reliability study
Authors: Brage K , Hjarbaek John , Kjaer Per , Ingwersen Kim G , Juul-Kristensen Birgit
Published: May 2019

Objectives

The reliability of ultrasonic strain elastography (SEL) used to detect abnormalities in the supraspinatus tendon is unclear. Thus, the aim of this study was to investigate the reliability of SEL in the supraspinatus tendon.

Design

An intra-rater and inter-rater reliability study.

Setting

A single-centre study conducted at the University of Southern Denmark.

Participants

Twenty participants with shoulder pain and MRI-verified supraspinatus tendinosis and 20 asymptomatic participants (no MRI).

Primary and secondary outcome measures

Raw values (RAW) and ratios (deltoid muscle (DELT) and gel pad (GEL) as reference tissues) were calculated and mean values of measurements from three regions of the supraspinatus tendon were reported. Colour scale ratings and number of yellow/red lesions from the three areas were also included.

Results

Intra-rater reliability showed intraclass correlation coefficients (ICCs) for RAW, DELT and GEL: 0.97 (minimal detectable change (MDC): 0.28 (6.36% of the mean)), 0.89 (MDC: 2.91 (20.37%)) and 0.73 (MDC: 1.61 (58.82%)), respectively. The ICCs for inter-rater reliability were 0.89 (MDC: 0.47 (10.53%)), 0.78 (MDC: 3.69 (25.51%)) and 0.70 (MDC: 1.75 (62.63%)), respectively.

For colour scale ratings, intra-rater reliability (linear weighted kappa) ranged from 0.76 to 0.79, with the inter-rater reliability from 0.71 to 0.81. For the number of lesions, intra-rater reliability ranged from 0.40 to 0.82 and inter-rater reliability from 0.24 to 0.67.

Conclusions

Intra-rater and inter-rater reliability were excellent for raw values and for ratios with deltoid muscle as the reference tissue, and good for ratios with gel pad as the reference tissue. The reliability of colour scale ratings was substantial-to-almost perfect, and for the number of lesions fair-to-almost perfect.

Although high reliability was found, validity and responsiveness of these elastographic methods needs further investigation.

Ethics approval

The study protocol was approved by the Ethics Committee for the Region of South Denmark (S-20160115) and reported to the Danish Data Protection Agency (2014-41-3266).
Type of sedation and the need for unplanned interventions during ERCP: analysis of the clinical outcomes research initiative national endoscopic database (CORI-NED)
Authors: Smith Zachary L , Nickel Katelin B , Olsen Margaret A , Vargo John J , Kushnir Vladimir M
Published: May 2019

Background and aims

Recent studies suggest that sedation provided by anaesthesia professionals may be less protective against serious adverse events than previously believed, however, data are lacking regarding endoscopic retrograde cholangiopancreatography (ERCP). Using the clinical outcomes research initiative national endoscopic database (CORI-NED), we aimed to assess whether mode of sedation was associated with rates of unplanned interventions (UIs) during ERCP.

Patients and methods

All subjects from CORI-NED undergoing ERCP from 2004 to 2014 were identified and stratified into three groups based on the initial mode of anaesthesia: endoscopist-directed sedation (EDS), monitored anaesthesia care without an endotracheal tube (MAC-WET) and general endotracheal anaesthesia (GEA). The primary outcome was UIs. To assess the impact of sedation mode on UIs, multivariable logistic regression models were created adjusting for demographic, physician and procedure-level variables.

Design

Population-based study.

Results

26 698 ERCPs were analysed (7588 EDS, 8395 MAC-WET, 10 715 GEA). UIs occurred in 320 ERCPs (1.2%). EDS was associated with a higher risk of UIs compared with sedation administered by an anaesthesia professional (OR 1.86, 95% CI 1.44 to 2.42). Additional factors associated with a higher risk of UIs included ASA class IV compared with class II (OR 3.18, 95% CI 2.00 to 5.06) and ERCPs done in community (OR 1.41, 1.04 to 1.91) and health maintenance organisations (OR 3.75, 2.01 to 6.99) hospitals.

Conclusion

EDS is associated with a higher risk of UIs during ERCP compared with sedation administered by an anaesthesia professional. Higher ASA class and procedures performed in non-university hospitals were also associated with a higher risk of UIs. This study suggests that, when available, sedation using an anaesthesia professional should be utilised for ERCP.
Using hospital discharge data for injury research or surveillance? An observational study illustrating the impact of administrative change
Authors: Davie Gabrielle , Barson Dave , Simpson Jean C , Lilley Rebbecca , Gulliver Pauline , Cryer Colin
Published: May 2019

Introduction

Hospital discharge data provide an important basis for determining priorities for injury prevention and monitoring trends in incidence. This study aims to illustrate the impact of a recent change in administrative practice on estimates of hospitalised injury incidence and to investigate the extent to which different case selection affects trends in injury incidence rates.

Methods

New Zealand (NZ) hospital discharges (2000–2014) with a primary diagnosis of injury were identified. Additional case selection criteria included first admissions only, and for serious injury, a high threat-to-life estimate. Comparisons were made, over time and by District Health Board, between hospitalised injury incidence estimates that included, or not, short-stay emergency department (SSED) discharges.

Results

Of the 1 229 772 injury hospital discharges, 365 114 were SSED; 16% of the annual total in 2000, 38% in 2014. Identification of readmissions prior to the exclusion of SSED discharges resulted in 30 724 cases being erroneously removed. Age-standardised rates of hospitalised injury over the 15-year period increased by, on average, 2.7% per year when SSED discharges were included; there was minimal secular change (−0.2%) when SSEDs were excluded. For serious hospitalised injury, the annual increase was 2.3% when SSED was included compared with 1.1% when SSEDs were excluded.

Conclusion

Spurious trends in hospitalised injury incidence can result when administrative practices are not appropriately accounted for. Exclusion of SSED discharges before the identification of readmissions and the use of a severity threshold are recommended to minimise the reporting bias in NZ hospitalised injury incidence estimates.
Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis
Authors: Loane Clare , Argyropoulos Georgios P D , Roca-Fernández Adriana , Lage Carmen , Sheerin Fintan , Ahmed Samrah , Zamboni Giovanna , Mackay Clare , Irani Sarosh R , Butler Christopher R
Published: May 2019

Objective

Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment.

Method

A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined.

Results

Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531).

Conclusion

VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy.