bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of lithium response using clinical data
Authors: Nunes A. , Ardau R. , Berghöfer A. , Bocchetta A. , Chillotti C. , Deiana V. , Garnham J. , Grof E. , Hajek T. , Manchia M. , Müller‐Oerlinghausen B. , Pinna M. , Pisanu C. , O’Donovan C. , Severino G. , Slaney C. , Suwalska A. , Zvolsky P. , Cervantes P. , del Zompo M. , Grof P. , Rybakowski J. , Tondo L. , Trappenberg T. , Alda M.
Published: October 2019

Objective

Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers.

Method

Our data are the largest existing sample of direct interview‐based clinical data from lithium‐treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR—as defined by the previously validated Alda scale—against 180 clinical predictors.

Results

Under appropriate cross‐validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78–0.82) and a Cohen kappa of 0.46 (0.4–0.51). The model demonstrated a particularly low false‐positive rate (specificity 0.91 [0.88–0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative.

Conclusion

Clinical data can inform out‐of‐sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between‐site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between‐ and within‐site heterogeneity, and further testing such models on new external datasets.
Early life temperamental anxiety is associated with excessive alcohol intake in adolescence: A rhesus monkey (Macaca mulatta) model
Authors: Wood Elizabeth K. , Kruger Ryno , Cash Elysha , Lindell Stephen G. , Schwandt Melanie L. , Barr Christina S. , Suomi Stephen J. , Higley J. Dee
Published: October 2019

Teenage alcohol abuse is a major health concern, particularly because the majority of alcohol consumed by teenagers is via binge drinking, a known risk factor for increasing the likelihood for the development of future alcohol use disorders (AUDs). Identifying individuals at risk for excessive alcohol intake in adolescence is a step toward developing effective preventative measures and intervention programs. As adults with AUDs tend to self‐medicate their anxiety with alcohol, this longitudinal study assesses the role of infant anxiety‐like temperament in the development of adolescent alcohol abuse using a nonhuman primate model. From birth until they were 5 months of age, behaviors of 64 rhesus monkeys (Macaca mulatta) were coded twice a week using an objective mother‐infant scoring system that included behaviors traditionally used to assess anxiety and fearfulness in rhesus monkeys. When subjects were four months old, plasma cortisol was obtained. When subjects were adolescents (Mage = 44.88 months), another plasma cortisol sample was obtained about one month prior to allowing them unfettered access to an 8.4% (v/v) aspartame‐sweetened alcohol solution for one hour a day over five‐to‐seven weeks. Results showed that behavioral indications of anxiety‐like temperament in infancy, including high levels of mother‐infant mutual ventral contact, low levels of environmental exploration, and low levels of interactions with peers were predictive of high adolescent alcohol intake (ie, drinking to intoxication). Plasma cortisol levels in infancy were positively correlated with plasma cortisol in adolescence, and both were positively correlated with high adolescent alcohol intake. Our findings indicate that high levels of traditional anxiety‐like behaviors measured in the context of mother‐infant interactions, coupled with high infant and adolescent plasma cortisol, are associated with binge‐like high alcohol intake in adolescence, suggesting that individuals at risk for developing an AUD later in life may be determined, at least in part, by assessing their physiological and behavioral propensity for anxiety early in life.
Using a species distribution model to guide NSW surveys of the long‐footed potoroo (Potorous longipes)
Authors: Wauchope‐Drumm Mareshell , Bentley Joss , Beaumont Linda J. , Baumgartner John B. , Nipperess David A.
Published: October 2019

Knowledge of threatened species’ distributions is essential for effective conservation decision‐making. Species distribution models (SDMs) are widely used to map species’ geographic ranges, identify new areas of suitable habitat and guide field surveys. In New South Wales (NSW), Australia, there are grave doubts about whether populations of the critically endangered long‐footed potoroo (Potorous longipes) remain extant, and identification of occupied sites is a high priority for its conservation. We used an SDM (Maxent) to identify regions in NSW that may have suitable habitat for the potoroo. The SDM was built with seven climate layers and had strong predictive performance (cross‐validated AUC = 0.94). We then combined this information on habitat suitability with vegetation and topography, to identify 58 survey sites across NSW. From April 2016 to May 2017, we undertook six field trips deploying six to eight cameras at each site for 52–63 days, resulting in 25 120 camera trap nights. A total of 215 759 images captured 43 native and feral animal species, but no long‐footed potoroos. Following the survey, newly available, independent presence and absence data were used to validate our model. A Kruskal–Wallis H test indicated that habitat suitability values were significantly higher at presence locations than absence locations (H = 58.66, d.f. = 1, P < 0.001). Finally, we refitted the Maxent model with the new data and identified additional regions that future surveys could explore. We conclude, however, that if the long‐footed potoroo remains extant in NSW, it is extremely rare.
Anticipating white‐nose syndrome in the Southern Hemisphere: Widespread conditions favourable toPseudogymnoascus destructanspose a serious risk to Australia's bat fauna
Authors: Turbill Christopher , Welbergen Justin A.
Published: October 2019

There is a serious concern that white‐nose syndrome (WNS), a fungal disease causing severe population declines in North American bats, could soon threaten bats on the Australian continent. Despite an ‘almost certain' risk of incursion within the next ten years, and high virulence in naïve bat populations, we remain uncertain about the vulnerability of Australian bats toWNS. In this study, we intersected occurrences for the 27 cave roosting bat species in Australia with interpolated data on mean annual surface temperature, which provides a proxy for thermal conditions within a cave and hence its suitability for growth by the fungal pathogenPseudogymnoascus destructans. Our analysis identifies favourable roost thermal conditions within 30–100% of the ranges of eight bat species across south‐eastern Australia, including for seven species already listed as threatened with extinction. These results demonstrate the potential for widespread exposure toP. destructansand suggest thatWNScould pose a serious risk to the conservation of Australia's bat fauna. The impacts of exposure toP. destructanswill depend, however, on the sensitivity of bats to developingWNS, and a more comprehensive vulnerability assessment is currently prevented by a lack of information on the hibernation biology of Australian bats. Thus, given the clear potential for widespread exposure of Australia's bats toP. destructansdemonstrated by our study, two specific policy actions seem justified: (i) urgent implementation of border controls that identify and decontaminate cave‐associated fomites and (ii) dedicated funding to enable research on key aspects of bat winter behaviour and hibernation physiology. Further, as accidental translocation of this fungus could also pose a risk to other naïve bat faunas in cooler regions of southern Africa and South America, we argue that a proactive, globally coordinated approach is required to understand and mitigate the potential impacts ofWNSspreading to Southern Hemisphere bats.
Red blood cell transfusion in surgery: an observational study of the trends in the USA from 2011 to 2016
Authors: Nordestgaard A. T. , Rasmussen L. S. , Sillesen M. , Steinmetz J. , Eid A. I. , Meier K. , Kaafarani H. M. A. , Velmahos G. C.
Published: October 2019

Guidelines recommend restrictive red blood cell transfusion strategies. We conducted an observational study to examine whether the rate of peri‐operative red blood cell transfusion in the USA had declined during the period from 01 January 2011 to 31 December 2016. We included 4,273,168 patients from all surgical subspecialties. We examined parallel trends in rates of the following: pre‐operative transfusion; prevalence of bleeding disorders and coagulopathy; and minimally invasive procedures. To account for changes in population and procedure characteristics, we performed multivariable logistic regression to assess whether the risk of receiving a transfusion had declined over the study period. Clinical outcomes included peri‐operative myocardial infarction, stroke and all‐cause mortality at 30 days. Peri‐operative red blood cell transfusion rates declined from 37,040/441,255 (8.4%) in 2011 to 46,845/1,000,195 (4.6%) in 2016 (p < 0.001) across all subspecialties. Compared with 2011, the corresponding adjusted OR (95%CI) for red blood cell transfusion decreased gradually from 0.88 (0.86–0.90) in 2012 to 0.51 (0.50–0.51) in 2016 (p < 0.001). Pre‐operative red blood cell transfusion rates and the prevalence of bleeding disorders decreased, whereas haematocrit levels and the proportion of minimally invasive procedures increased. Compared with 2011, the adjusted hazard ratios (95%CI) in 2012 and 2016 were 0.96 (0.90–1.02) and 1.05 (0.99–1.11) for myocardial infarction, 0.91 (0.83–0.99) and 0.99 (0.92–1.07) for stroke and 0.98 (0.94–1.02) and 0.99 (0.96–1.03) for all‐cause mortality. Use of peri‐operative red blood cell transfusion declined from 2011 to 2016. This was not associated with an increase in adverse clinical outcomes.
Acute spinal cord injuries before and after the New Zealand Spinal Cord Impairment Action Plan
Authors: Lin Peny , Vandal Alain C. , Patel Alpesh
Published: October 2019

Background

Early medical and surgical intervention in acute spinal cord injuries can improve long‐term functional outcomes. This study aims to observe the effects of the New Zealand (NZ) Spinal Cord Impairment Action Plan on timing to acute decompression and comparing this to the period prior to the policy change.

Method

Data were collected in the form a retrospective audit from medical records of 12 patients admitted to Middlemore Hospital from 2010 to 2013 prior to the NZ Spinal Cord Impairment Action Plan, and 11 patients from 2014 to 2015 following the policy change. Time of decompression is defined as either closed reduction or open reduction plus decompression. Patients were transferred from an initial regional hospital to Middlemore Hospital or directly to Middlemore Hospital following injury. Important time points were compared before and after the NZ Spinal Cord Impairment Action Plan.

Results

Cox regression modelling was used to compare statistical data. Following the regional policy change, patients had a shorter time of transfer between hospitals, pre‐surgical work up, and hence shorter time to decompression. The mean time of injury to decompression before the policy change is 57.8 and 24.9 h after.

Conclusion

Since implementing the NZ Spinal Cord Impairment Action Plan, time to decompression has been significantly reduced compared with the same group prior.
Intraoperative nerve monitoring in endocrine surgery: prevalence and reasons for its use in Australia and New Zealand
Authors: Leong David Chee Weng , Lo Johnny , Ryan Simon , Nguyen Hieu , Lisewski Dean
Published: October 2019

Background

Intraoperative nerve monitoring (IONM) has increasingly been used in thyroid surgery by general, endocrine and head and neck surgeons. The purpose of this paper was to explore the prevalence and reasons for the usage of IONM in endocrine surgery in Australia and New Zealand.

Methods

A survey was sent to general surgeons registered with the Royal Australasian College of Surgeons involved in endocrine surgery and members of the Australian and New Zealand Endocrine Surgeons. Users were divided into surgeon type, area of work, hospital type and volume of surgery. These data were analysed with univariate and multivariate logistic regression models.

Results

Significant differences in IONM usage levels were observed between endocrine and general surgeons, area of work and volume of surgery performed. Endocrine surgeons are significantly more likely to use IONM than general surgeons. Surgeons who work in tertiary hospitals are more likely to use IONM as compared to those working in district hospitals. Surgeons who perform less than 100 thyroidectomies were more likely to be users of IONM.

Conclusion

IONM is not routinely used in thyroid surgery in Australia and New Zealand. The main reasons for the use of IONM given in our study by routine users were to establish familiarity of equipment and medicolegal reasons. Selective users chose as the most common reasons, a documented pre‐existing unilateral nerve paresis or a hostile surgical field. Non‐users stated that there was conflicting evidence that it improves outcomes and increased costs.
Babies in occiput posterior position are significantly more likely to require an emergency cesarean birth compared with babies in occiput transverse position in the second stage of labor: A prospective observational study
Authors: Tempest Nicola , Lane Steven , Hapangama Dharani ,   UK Audit Ressearch Trainee Collaborative in Obstetrics, Gynecology (UK‐ARCOG)
Published: October 2019

Introduction

Malposition complicates 2‐13% of births at delivery, leading to increased obstetric interventions (cesarean section and instrumental delivery) and higher rates of adverse fetal and maternal outcomes. Limited data are available regarding the likely rates of obstetric intervention and subsequent neonatal and maternal outcomes of births with babies in persistent occiput posterior position vs those in persistent occiput transverse position. The UK Audit and Research trainee Collaborative in Obstetrics and Gynecology (UK‐ARCOG) network set out to collect data prospectively at delivery on final mode of delivery and immediate outcomes.

Material and methods

The UK‐ARCOG network collected data on all births with malposition of the fetal head complicating the second stage of labor (n = 838) (occiput posterior/occiput transverse) requiring rotational vaginal operative birth or emergency cesarean to expedite delivery across 66 participating UK National Health Service maternity units over a 1‐month period. The outcomes considered were the need for emergency cesarean section without a trial of instrumental delivery, success of the first method of delivery employed in achieving a vaginal delivery and neonatal/maternal outcomes.

Results

Obstetricians regarded assistance with an operative vaginal delivery method to be unsafe in 15% of babies in occiput posterior position and 6.1% of babies in occiput transverse position, and they were delivered by primary emergency cesarean section. When vaginal delivery was deemed safe (defined as attempted assisted vaginal rotational delivery), the first instrument attempted was successful in 74.4% of occiput posterior babies and 79.3% of occiput transverse babies.

Conclusions

Our data facilitates decision making by obstetricians to increase safety of assisted rotational operative delivery of a malpositioned baby at initial assessment and in counseling women. Until data from a well‐designed randomized controlled trial of instrumental delivery vs emergency cesarean section are available, this manuscript provides contemporaneous national data from a high resource setting within a structured training program, to assist the selection of an appropriate instrument/method for the delivery of a malpositioned baby.
Pain‐related increase in serotonin transporter gene methylation associates with emotional regulation in 4.5‐year‐old preterm‐born children
Authors: Provenzi Livio , Fumagalli Monica , Scotto di Minico Giunia , Giorda Roberto , Morandi Francesco , Sirgiovanni Ida , Schiavolin Paola , Mosca Fabio , Borgatti Renato , Montirosso Rosario
Published: October 2019

Aim

The main goal of this study was to assess the association between pain‐related increase in serotonin transporter gene (SLC6A4) methylation and emotional dysregulation in 4.5‐year‐old preterm children compared with full‐term matched counterparts.

Methods

Preterm (n = 29) and full‐term (n = 26) children recruited from two Italian hospitals were followed‐up from October 2011 to December 2017. SLC6A4 methylation was assessed from cord blood at birth from both groups and peripheral blood at discharge for preterm ones. At 4.5 years, emotional regulation (ie, anger, fear and sadness) was assessed through an observational standardised procedure.

Results

Preterm children (18 females; mean age = 4.5, range = 4.3‐4.8) showed greater anger display compared with full‐term controls (14 females; mean age = 4.5, range = 4.4‐4.9) in response to emotional stress. Controlling for adverse life events occurrence from discharge to 4.5 years and SLC6A4 methylation at birth, CpG‐specific SLC6A4 methylation in the neonatal period was predictive of greater anger display in preterm children but not in full‐term ones.

Conclusion

These findings contribute to highlight how epigenetic regulation of serotonin transporter gene in response to NICU pain exposure contributes to long‐lasting programming of anger regulation in preterm children.
Vascular adenosine monophosphate‐activated protein kinase: Enhancer, brake or both?
Authors: Chen Hui , Vanhoutte Paul Michel , Leung Susan Wai Sum
Published: October 2019

Adenosine monophosphate‐activated protein kinase (AMPK), expressed/present ubiquitously in the body, contributes to metabolic regulation. In the vasculature, activation of AMPK is associated with several beneficial biological effects including enhancement of vasodilatation, reduction of oxidative stress and inhibition of inflammatory reactions. The vascular protective effects of certain anti‐diabetic (metformin and sitagliptin) or lipid‐lowering (simvastatin and fenofibrate) therapeutic agents, of active components of Chinese medicinal herbs (resveratrol and berberine) and of pharmacological agents (AICAR, A769662 and PT1) have been attributed to the activation of AMPK (in endothelial cells, vascular smooth muscle cells and/or perivascular adipocytes), independently of changes in the metabolic profile (eg glucose tolerance and/or plasma lipoprotein levels), leading to improved endothelium‐derived nitric oxide‐mediated vasodilatation and attenuated endothelium‐derived cyclooxygenase‐dependent vasoconstriction. By contrast, endothelial AMPK activation with pharmacological agents or by genetic modification is associated with reduced endothelium‐dependent relaxations in small blood vessels and elevated systolic blood pressure. Indeed, AMPK activators inhibit endothelium‐dependent hyperpolarization (EDH)‐type relaxations in superior mesenteric arteries, partly by inhibiting endothelial calcium‐activated potassium channel signalling. Therefore, AMPK activation is not necessarily beneficial in terms of endothelial function. The contribution of endothelial AMPK in the regulation of vascular tone, in particular in the microvasculature where EDH plays a more important role, remains to be characterized.
Differences in nasal immunoglobulin A responses to influenza vaccine strains after live attenuated influenza vaccine (LAIV) immunization in children
Authors: Turner P J , Abdulla A F , Cole M E , Javan R R , Gould V , O'Driscoll M E , Southern J , Zambon M , Miller E , Andrews N J , Höschler K , Tregoning J S
Published: October 2019

Different vaccine strains included in the live attenuated influenza vaccine (LAIV) have variable efficacy. The reasons for this are not clear and may include differences in immunogenicity. We report a Phase IV open-label study on the immunogenicity of a single dose of quadrivalent LAIV (Fluenz™ Tetra) in children during the 2015/16 season, to investigate the antibody responses to different strains. Eligible children were enrolled to receive LAIV; nasal samples were collected before and approximately 4 weeks after immunization. There was a significant increase in nasal immunoglobulin (Ig)A to the H3N2, B/Victoria lineage (B/Brisbane) and B/Yamagata lineage (B/Phuket) components, but not to the H1N1 component. The fold change in nasal IgA response was inversely proportional to the baseline nasal IgA titre for H1N1, H3N2 and B/Brisbane. We investigated possible associations that may explain baseline nasal IgA, including age and prior vaccination status, but found different patterns for different antigens, suggesting that the response is multi-factorial. Overall, we observed differences in immune responses to different viral strains included in the vaccine; the reasons for this require further investigation.
The documented layer of children's rights in care order decision‐making
Authors: Hoikkala Susanna , Pösö Tarja
Published: October 2019

The recognition of children as rights holders is a true challenge for any policy and practice that involves children, but it is even more so for making decisions about taking children into care. This article departs from the view that when children are perceived as bearers of rights, this should also be reflected in the institutional documents of decision‐making. That is why the documented layer of decisions about taking a child into care is examined here. The empirical data consist of documents of hearings (prehearing and hearing reports) in which children (33) are asked to give their view about a proposed care order and placement in Finland.

The documented layers of involving children as rights holders are divided into two types: a minimalist type and a more individualised, thorough and detailed type. The former type represents children as rights holders in a routinised manner, whereas the latter one treats them in a particularised manner: how this particular child in this particular hearing received and gave information and on what grounds her/his view rested. As the documents may have some controversial implications, the recording of children as rights holders should not be treated as an isolated and technical issue.
Sense of Place and Feelings of Safety: Examining Young Adults’ Experiences of their Local Environment using Mobile Surveys
Authors: Chataway Michael L.
Published: October 2019

This study aims to examine feelings of safety and the correlates to feelings of decreased worry toward crime within individuals’ proximate environments. Data from adults living in Southeast Queensland ( N = 72) were collected using a mobile application. Findings of a thematic analysis of these data suggest that safety perceptions are primarily driven by (a) physical features of the proximate environment, (b) social characteristics of a place, and (c) location familiarity or awareness. This study concludes with a discussion of how these themes may be leveraged to develop more focused fear–reduction strategies that involve modifying features of the physical environment, improving social characteristics of place and increasing knowledge/awareness of place.
“Smack in the Middle”: Urban Governance and the Spatialization of Overdose Epidemics
Authors: McKelvie Sylvia
Published: October 2019

In recent years, cities in North America have declared public health emergencies in response to opioid–related overdoses and fatalities. Municipalities are reacting with various interventions and degrees of urgency, whereas harm reduction organizations coordinate the street–level fight against death. Though drug use has long been concentrated in urbanized and downtown areas, these neighborhoods are being addressed with new national attention. This article draws on qualitative interviews with participants in the Downtown Eastside (DTES) in Vancouver and the Tenderloin in San Francisco. I highlight two interconnected themes: (1) the legacy of distrust between municipal officials and drug users and (2) the disconnection between “epidemics” as narrowly constructed public health emergencies and the needs of communities. Findings show ongoing struggles with “progressive” urban agendas. San Francisco minimized fatalities thanks to the early introduction of unregulated naloxone; however, new anti–homelessness legislation and police–led initiatives continue to create social upheaval for drug users. In comparison, the rollout of Vancouver's naloxone program arrived 10 years too late. Organizations are attempting to amplify access to safe injection and overdose prevention sites in the DTES. Using interurban analysis, overdose epidemics can be conceptualized as sociospatial fields of power, providing greater insight into urban marginality and health inequalities.
Assessing effects of federal crop insurance supply on acreage and yield of specialty crops
Authors: Shi Jian , Wu JunJie , Olen Beau
Published: October 2019

Crop insurance may affect harvested acreage and yield by influencing producers’ behavior such as land allocation and input use. Although specialty crops are a major source of farm income, especially on the U.S. west coast, they have not received as much attention as field crops in previous empirical studies. This paper assesses the effect of moral hazard and adverse selection associated with the federal crop insurance program (FCIP) on the acreage and yield of major specialty crops in California. An econometric method that expands the switching regression model is developed to assess the effect. Results suggest that federal crop insurance can change specialty crop growers’ production responses to climate and soil conditions. The moral hazard effect tends to increase the acreage and yield of the specialty crops, whereas the adverse selection effect tends to have the opposite effect. The overall effect of the FCIP on acreage and yield of specialty crops is found to be moderate.
MATN1‐AS1 promotes glioma progression by functioning as ceRNA of miR‐200b/c/429 to regulate CHD1 expression
Authors: Zhu Jun , Gu WeiTing , Yu Cai
Published: October 2019

Objectives

Long non‐coding RNA (lncRNA) MATN1‐AS1 is a newfound lncRNA that has been rarely explored in cancers. Herein, we would like to investigate its role in glioma.

Materials and methods

qRT‐PCR was conducted to examine gene expression in glioma. Then, MTT assay, colony formation assay and flow cytometry analysis were applied to evaluate the function of MATN1‐AS1 on glioma cells. Western blot was performed to measure the protein levels of genes. Besides, the luciferase reporter assay, RNA pull‐down assay, RIP assay and Spearman's correlation analysis were also performed as needed.

Results

Firstly, a data from TCGA showed that MATN1‐AS1 might be largely implicated in glioma. Meanwhile, MATN1‐AS1 upregulation confirmed in glioma predicted poor clinical outcomes. Functionally, MATN1‐AS1 knockdown restrained cell proliferation but stimulated apoptosis in vitro and repressed tumour growth in vivo. Mechanistic investigations validated that MATN1‐AS1 functioned as a ceRNA for miR‐200b/c/429 to upregulate CHD1 which was also verified to exert a growth‐promoting role in glioma cells here. Importantly, both CHD1 overexpression and miR‐200b/c/429 inhibition could rescue the obstructive role of MATN1‐AS1 silence in glioma cells.

Conclusions

MATN1‐AS1 promotes glioma progression through regulating miR‐200b/c/429‐CHD1 axis, suggesting MATN1‐AS1 as a probable target for glioma treatment.
Use of Idarucizumab to reverse the anticoagulant effect of dabigatran in cardiac transplant surgery. A multicentric experience in Spain
Authors: Crespo‐Leiro Maria G. , López‐Vilella Raquel , López Granados Amador , Mirabet‐Pérez Sonia , Díez‐López Carles , Barge‐Caballero Eduardo , Segovia‐Cubero Javier , González‐Vilchez Francisco , Rangel‐Sousa Diego , Blasco‐Peiró Teresa , de la Fuente‐Galán Luis , Díaz‐Molina Beatriz , Zatarain‐Nicolás Eduardo , Carrasco Ávalos Francisco , Almenar‐Bonet Luis
Published: October 2019

Background

Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin inhibitor, is increasingly used for anticoagulation in patients with non‐valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab.

Aim

To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT.

Methods

Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery.

Results

Fifty‐three patients were included (81.1% male). 7.5% required re‐operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30‐day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post‐HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post‐HT death was associated with bleeding.

Conclusions

These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations.
Complete endoscopic removal of a hemorrhoid medication tube as an anorectal foreign body
Authors: Soga Koichi , Kassai Kyoichi , Itani Kenji
Published: October 2019

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Success or failure of blinding in randomized controlled trials
Authors: Day Steven M
Published: October 2019

This commentary is on the letters to the editor by Hastings‐Ison and Graham and Copeland et al. on page 259 of this issue and on page 260 of this issue.
Expanding transformative experience
Authors: Carel Havi , Kidd Ian James
Published: October 2019

We develop a broader, more fine‐grained taxonomy of forms of transformative experience, inspired by the work of L. A. Paul. Our vulnerability to such experiences arises, we argue, due to the vulnerability, dependence, and affliction intrinsic to the human condition. We use this trio to distinguish a variety of positively, negatively, and ambivalently valenced forms of epistemically and/or personally transformative experiences. Moreover, we argue that many transformative experiences can arise gradually and cumulatively, unfolding over the course of longer periods of time.
Effect of a novel prime‐and‐rinse approach on short‐ and long‐term dentin bond strength of self‐etch adhesives
Authors: Li Mingxing , Xu Jingqiu , Zhang Ling , Wang Chaoyang , Jin Xiaoting , Hong Yan , Fu Baiping , Hannig Matthias
Published: October 2019

This study investigated the effects of the prime‐and‐rinse approach, using a 10‐methacryloyloxydecyl dihydrogen phosphate (MDP)‐containing primer, on the short‐ and long‐term dentin microtensile bond strengths (MTBSs) of mild self‐etch adhesives. Half of sixty human midcoronal dentin surfaces were polished as control (self‐etch approach), and the other half were polished and further treated with a 15% MDP‐containing primer and thoroughly sprayed with water as prime‐and‐rinse approach. The dentin surfaces were treated with a self‐etch adhesive, and a composite resin was placed on the surfaces. The following materials were used: Clearfil S3 Bond+Clearfil Majesty; G‐Bond+Gradia Direct; Adper Easy One+Z250; and i Bond+Charisma. The MTBS was examined after 24 h and 14 months in water storage. The resin–dentin interfaces were analysed using scanning electron microscopy/transmission electron microscopy. Pretreated dentin surfaces were further analysed using scanning electron microscopy and micro‐Raman spectroscopy. Compared with the self‐etch approach, the prime‐and‐rinse approach significantly increased the dentin MTBS, regardless of the duration of storage. The scanning electron microscopy/transmission electron microscopy findings revealed that the prime‐and‐rinse approach removed most of the dentin smear layer. The Raman spectra of the MDP‐treated dentin reveal the characteristic spectra of collagen, hydroxyapatite, and the monomer. Therefore, the prime‐and‐rinse approach using MDP‐containing primers prior to the application of mild self‐etch adhesives significantly increases the short‐ and long‐term MTBS of dentin.
Variable outcomes of hybridization between declining Alosa alosa and Alosa fallax
Authors: Taillebois Laura , Sabatino Stephen , Manicki Aurélie , Daverat Françoise , Nachón David José , Lepais Olivier
Published: October 2019

Hybridization dynamics between co‐occurring species in environments where human‐mediated changes take place are important to quantify for furthering our understanding of human impacts on species evolution and for informing management. The allis shad Alosa alosa (Linnaeus, 1758) and twaite shad Alosa fallax (Lacépède, 1803), two clupeids sister species, have been severely impacted by human activities across Europe. The shrinkage of A. alosa distribution range along with the decline of the remaining populations' abundance threatens its persistence. The main objective was to evaluate the extent of hybridization and introgression between those interacting species. We developed a set of 77 species‐specific SNP loci that allowed a better resolution than morphological traits as they enabled the detection of hybrids up to the third generation. Variable rates of contemporary hybridization and introgression patterns were detected in 12 studied sites across the French Atlantic coast. Mitochondrial markers revealed a cyto‐nuclear discordance almost invariably involving A. alosa individuals with an A. fallax mitochondrial DNA and provided evidence of historical asymmetric introgression. Overall, contemporary and historical introgression revealed by nuclear and mitochondrial markers strongly suggests that a transfer of genes occurs from A. fallax toward A. alosa genome since at least four generations. Moreover, the outcomes of introgression greatly depend on the catchments where local processes are thought to occur. Undoubtedly, interspecific interaction and gene flow should not be overlooked when considering the management of those species.
Response of foundation macrophytes to near‐natural simulated marine heatwaves
Authors: Saha Mahasweta , Barboza Francisco R. , Somerfield Paul J. , Al‐Janabi Balsam , Beck Miriam , Brakel Janina , Ito Maysa , Pansch Christian , Nascimento‐Schulze Jennifer C. , Jakobsson Thor Stina , Weinberger Florian , Sawall Yvonne
Published: October 2019

Marine heatwaves have been observed worldwide and are expected to increase in both frequency and intensity due to climate change. Such events may cause ecosystem reconfigurations arising from species range contraction or redistribution, with ecological, economic and social implications. Macrophytes such as the brown seaweed Fucus vesiculosus and the seagrass Zostera marina are foundation species in many coastal ecosystems of the temperate northern hemisphere. Hence, their response to extreme events can potentially determine the fate of associated ecosystems. Macrophyte functioning is intimately linked to the maintenance of photosynthesis, growth and reproduction, and resistance against pathogens, epibionts and grazers. We investigated morphological, physiological, pathological and chemical defence responses of western Baltic Sea F. vesiculosus and Z. marina populations to simulated near‐natural marine heatwaves. Along with (a) the control, which constituted no heatwave but natural stochastic temperature variability (0HW), two treatments were applied: (b) two late‐spring heatwaves (June, July) followed by a summer heatwave (August; 3HW) and (c) a summer heatwave only (1HW). The 3HW treatment was applied to test whether preconditioning events can modulate the potential sensitivity to the summer heatwave. Despite the variety of responses measured in both species, only Z. marina growth was impaired by the accumulative heat stress imposed by the 3HW treatment. Photosynthetic rate, however, remained high after the last heatwave indicating potential for recovery. Only epibacterial abundance was significantly affected in F. vesiculosus. Hence both macrophytes, and in particular F. vesiculosus, seem to be fairly tolerant to short‐term marine heatwaves at least at the intensities applied in this experiment (up to 5°C above mean temperature over a period of 9 days). This may partly be due to the fact that F. vesiculosus grows in a highly variable environment, and may have a high phenotypic plasticity.
Consequences of Groundwater‐Model Vertical Discretization in Risk‐Based Decision‐Making
Authors: White Jeremy T. , Knowling Matthew J. , Moore Catherine R.
Published: October 2019

One of the first and most important decisions facing practitioners when constructing a numerical groundwater model is vertical discretization. Several factors will influence this decision, such as the conceptual model of the system and hydrostratigraphy, data availability, resulting computational burden, and the purpose of the modeling analysis. Using a coarse vertical discretization is an attractive option for practitioners because it reduces data requirements and model construction efforts, can increase model stability, and can reduce computational demand. However, using a coarse vertical discretization as a form of model simplification is not without consequence; this may give rise to unwanted side‐effects such as biases in decision‐relevant simulated outputs. Given its foundational role in the modeled representation of the aquifer system, herein we investigate how vertical discretization may affect decision‐relevant simulated outputs using a paired complex‐simple model analysis. A Bayesian framework and decision analysis approach are adopted. Two case studies are considered, one of a synthetic, linked unsaturated‐zone/surface‐water/groundwater hydrologic model and one of a real‐world linked surface‐water/groundwater hydrologic‐nitrate transport model. With these models, we analyze decisions related to abstraction‐induced changes in ecologically important streamflow characteristics and differences in groundwater and surface‐water nitrate concentrations and mass loads following potential land‐use change. We show that for some decision‐relevant simulated outputs, coarse vertical discretization induces bias in important simulated outputs, and can lead to incorrect resource management action. For others, a coarse vertical discretization has little or no consequence for resource management decision‐making.
Effects of exercise in people with haemophilia: An umbrella review of systematic reviews and meta‐analyses
Authors: Siqueira Thais Cristina , Dominski Fábio Hech , Andrade Alexandro
Published: October 2019

Introduction

There is considerable evidence to indicate that exercise can have a positive impact on the treatment of people with haemophilia (PWH). However, there is a requirement for in‐depth and comprehensive studies.

Aim

This study aimed to analyse the evidence regarding the effects of exercise in PWH through an umbrella review of existing systematic reviews and meta‐analyses. The secondary objective was to analyse the quality of the evidence.

Methods

This umbrella review followed the PRISMA guidelines and was documented in the PROSPERO registry (CRD42019140785). We searched the PubMed, Web of Science, SPORTDiscus, Scopus, CINAHL and Cochrane Library databases. The methodological quality of the systematic reviews was assessed using AMSTAR 2.

Results

Out of a total of 1030 systematic reviews, 10 fulfilled the criteria. Only one study was classified as high quality, and half of the selected studies were classified as low or critically low quality according to AMSTAR 2. Furthermore, most reviews investigated the effects of strength training and aquatic training, with positive results associated with low adverse events. Range of motion, strength and pain were the most investigated variables. All reviews showed overlapping studies.

Conclusion

Exercise is an effective way to treat haemophilia and has a low incidence of related adverse events. However, caution is needed in the interpretation of the results due to half of the selected reviews showed low or critically low quality and only one have high quality.
Acid suppression therapy and its association with spontaneous bacterial peritonitis incidence: A systemic review and meta‐analysis
Authors: Lin Lin , Hou Lijun , Deng You , Zhao Tianming , Wang Bangmao , Sun Chao
Published: October 2019

Aim

It is well known that the use of proton pump inhibitor (PPI) is widespread in patients with liver cirrhosis. PPI counteracts H2 receptor inhibitor (H2RA) with its strong acid suppression effect. However, there is always a concern that PPI use may increase spontaneous bacteria peritonitis (SBP) development in cirrhotic patients. We aimed to investigate the association between acid suppression therapy (i.e. PPI or H2RA) and SBP through meta‐analysis.

Methods

We searched PubMed, Medline, Web of Science, Cochrane library, and Embase for relevant studies published up to April 2019. Pooled OR and 95% CI were calculated by a random‐effects model. Funnel plots and Egger's tests were performed for the evaluation of publication bias. Non‐parametric “trim‐and‐fill” tests were conducted for sensitivity analysis.

Results

A total of 20 original articles including 9566 cirrhotic patients were analyzed. The overall meta‐analysis highlighted that PPI use was associated with the risk of SBP (pooled OR 1.77, 95% CI 1.49–2.11). The conclusion was irrespective of study methods, whereas the result was inconsistent only in South America. However, the conclusion might not be stable enough and should be extrapolated with caution. Unlike PPI, we found H2RA was not associated with SBP (pooled OR 1.06, 95% CI 0.75–1.48).

Conclusions

In conclusion, PPI use, but not H2RA, will increase the incidence of SBP in cirrhotic patients. In addition, H2RA might be beneficial for patients who require long‐term acid suppression therapy.
Patterns of comorbidity and sociodemographic and psychosocial correlates among people living with HIV in South Carolina, USA
Authors: Yang X , Li X , Qiao S
Published: October 2019

Objectives

Prevention of comorbidity with HIV infection warrants more attention as people living with HIV (PLWH) tend to live longer in the era of effective antiretroviral therapy (ART). This study aimed to investigate the associations between various psychosocial variables and different comorbid conditions in South Carolina (SC), USA.

Methods

A cross‐sectional survey was conducted among PLWH from May to September 2018 in SC. Comorbid conditions were based on self‐report data and grouped into sexually transmitted infection (STI) comorbidities, noninfectious chronic comorbidities or any comorbidity. Multivariate logistic regression models were used to analyse the relevant associations.

Results

Among 402 participants, the prevalence of STI comorbidities, noninfectious chronic comorbidities, and any comorbidity was 61.7%, 21.9% and 69.4%, respectively. The multivariate analysis showed that higher depression scores were associated with an increased risk of any comorbidity, while higher anxiety scores were associated with an increased risk of STI comorbidities or any comorbidity. Higher resilience scores were associated with a decreased risk of noninfectious chronic comorbidities or any comorbidity.

Conclusions

The association between psychosocial factors and different types of comorbidity could inform holistic interventions, such as providing integrated mental health services (e.g. treating mental health problems or building resilience), to effectively cope with and manage the co‐existing medical conditions of PLWH.
Consumption as a social integration strategy in times of crisis: The case of vulnerable households
Authors: Arnal Sarasa María , de Castro Pericacho Carlos , Martín Martín María Paz
Published: October 2019

In this article, we focus on consumption in a context of economic hardship. From an empirical perspective, and using a qualitative methodology, we show how disadvantaged individuals and households maintain a level of consumption commensurate with the society in which they are integrated through a type of consumption conceived of here as “resilient”. Resilient consumption is characterized by being a type of expenditure oriented towards maintaining the role of consumer, that is, maintaining a minimum level of purchasing power, modifying to this end both the level and the structure of consumption, both of which are key elements in the resilience process. We identify five main strategies used by households that modify and restructure the consumption of basic goods and necessities in response to economic hardship. Key resilient consumption strategies include: reduction (cutting down on spending), substitution (replacement of one difficulty with another), compensation (pseudo‐consumption or reduced usage), transference (meta‐resilience) and integration (reinterpretation of difficulties as opportunities). We conclude that although consumption is a naturally resilient behaviour, in a crisis context, resilient practices focus on maintaining acquisition capacity in spite of reduced income.
Methylphenidate in children with monogenic obesity due to LEPR or MC4R deficiency improves feeling of satiety and reduces BMI‐SDS—A case series
Authors: Brandt Stephanie , von Schnurbein Julia , Lennerz Belinda , Kohlsdorf Katja , Vollbach Heike , Denzer Christian , Bode Harald , Hebebrand Johannes , Wabitsch Martin
Published: October 2019

Background

The clinical phenotype of patients with monogenic obesity due to mutations in the leptin receptor (LEPR) or melanocortin 4 receptor (MC4R) gene is characterized by impaired satiety and hyperphagia, leading to extreme, sometimes life‐threatening weight gain.

Subjects/methods

In a case series, we analysed the effect of an off‐label methylphenidate (MPH) use for 1 year as an individual treatment approach on eating behaviour (Child Eating Behaviour Questionnaire [CEBQ]), appetite (visual analogue scales) and body mass index (BMI) trajectories in five patients with severe obesity due to mutations in the LEPR (n = 3) or MC4R (n = 2) gene.

Results

After 1 year use of MPH (20 mg/day divided in two to three doses), BMI (Δ BMIT0−T1
: −0.7 ± 0.9 kg/m2), BMI standard deviation score (SDS) (Δ BMI‐SDST0−T1
: −0.32 ± 0.20), and %BMIP95 (Δ %BMIP95T0−T1
: −6.6 ± 7.8%) decreased. BMI‐SDS velocity decreased from +0.17 ± 0.22 to −0.30 ± 0.20. Appetite and CEBQ subscale scores for “food responsiveness” and “enjoyment of food” decreased. We observed adverse effects with increase in self‐reported frequency of disordered sleep, nervousness, hyperactivity, and tics.

Conclusions

The observed decrease in BMI trajectories with MPH use for one year is clinically meaningful in this group of patients, since the natural course would have been associated with a pronounced increase in BMI, leading to comorbidities and complications over time.