bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of single and multiple doses of elobixibat, an ileal bile acid transporter inhibitor, on chronic constipation: A randomized controlled trial
Authors: Kumagai Yuji , Amano Hideki , Sasaki Yoshinobu , Nakagawa Chie , Maeda Mika , Oikawa Ichiro , Furuie Hidetoshi
Published: June 2018

Aims

Elobixibat is a minimally absorbed ileal bile acid transporter inhibitor. This study aimed to investigate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of elobixibat in Japanese patients with chronic constipation.

Methods

This study consisted of single‐dose and multiple‐dose tests with a dose‐escalating design. Sixty patients including females and males were randomized into five dose levels of elobixibat (2.5, 5, 10, 15 or 20 mg, n = 10 per level) and corresponding placebo (n = 2 per group). A crossover design was used to examine food effect in single‐dose test. Patients received test tablets once daily for 14 days in multiple‐dose test. We assessed pharmacokinetic‐dose proportionality, levels of serum high‐ and low‐density lipoprotein cholesterol and plasma 7α‐hydroxy‐4‐cholesten‐3‐one (C4), food effect and sex‐specific effect. Adverse events and bowel functions such as bowel movements, stool consistency and straining were also evaluated.

Results

Food consumption reduced systemic exposure by around 80% [e.g. least squares mean (ratio of breakfast/no breakfast) maximum plasma concentration: 0.2085 (90% confidence interval, 0.1371–0.3172) at 15 mg] while increased plasma C4 level (P < 0.001). In the multiple‐dose test, elobixibat reduced low‐density lipoprotein cholesterol and increased C4 whilst unaltering high‐density lipoprotein cholesterol level. The increased spontaneous bowel movement frequency was correlated with higher dosage and higher C4 level (R2 = 0.5929 at Week 2). Adverse events were mainly gastrointestinal symptoms, most of which were mild.

Conclusions

Elobixibat should be taken before breakfast. Once‐daily administration of elobixibat was found to be safe and tolerated up to 20 mg in female and male patients with chronic constipation.
Good or bad? Ridesharing's impact on Canadian cities
Authors: Zwick Austin , Spicer Zachary
Published: July 2018

Ridesharing's phenomenal growth has been fueled by a combination of efficiency gains through technological innovation and disregard for current taxi regulations. The end effect has been the generation of significant consumer surplus, but at what social cost? This dialogue piece debates whether ridesharing services have been good or bad for Canadian cities and then reviews current regulatory status in Toronto and Vancouver.
Young Children's Theory of Mind Predicts More Sharing With Friends Over Time
Authors: Vonk Jennifer , Jett Stephanie E. , Tomeny Theodore S. , Mercer Sterett H. , Cwikla Julie
Published: June 2018

Children (predominantly white and middle class) between 3 and 6 years (M = 55.12 months, N = 145 at Time 1, N = 102 at Time 2) participated in the prosocial choice test at two time points approximately 10 months apart. Children could share with strangers, close friends, nonfriends, and in a control, no recipient condition. Children shared more rewards with friends over time. Age interacted with recipient type such that older children had a higher probability of prosocial allocations toward friends and strangers compared to younger children. Theory of mind (ToM) predicted more prosocial allocations to friends over time, and the youngest children with higher ToM scores showed the largest increase in sharing with friends over time.
The Racovitzan impediment and the hidden biodiversity of unexplored environments
Authors: Ficetola Gentile Francesco , Canedoli Claudia , Stoch Fabio
Published: July 2018

Article impact statement: Biodiversity of unexplored and unmapped environments cannot be conserved until they have been described, mapped, and analyzed.
p63 and smooth muscle actin expression in low‐grade spiradenocarcinomas in a case of CYLD cutaneous syndrome
Authors: Hoyle Aoisha , Davies Kerry , Rajan Neil , Melly Lucy
Published: July 2018

Low‐grade spiradenocarcinoma is a rare skin tumor, with fewer than six reported cases, arising in the context of CYLD cutaneous syndrome (CCS; syn: Brooke‐Spiegler syndrome [BSS]). We report two independent cases of spiradenocarcinoma arising in a 50‐year‐old man with CCS. The tumors grew rapidly, prompting clinical excision. The histologic features in our cases corresponded to the salivary gland type basal cell adenocarcinoma‐like pattern, low grade (BCAC‐LG), that has been previously recognized as a recurrent finding in CCS. We performed genetic testing of the patient and found a novel mutation in CYLD. Recognition of low‐grade spiradenocarcinoma can be difficult for the pathologist as the features can be subtle, especially in those cases where the transition from benign to malignant tumor is gradual. We examined p63 and smooth muscle actin (SMA) expression patterns in BCAC‐LG and compared it with the expression pattern in the precursor spiradenoma. Our report provides information on two rare tumors in the context of CCS and suggests that the pattern of p63 and SMA staining may aid pathological detection of the BCAC‐LG subtype of spiradenocarcinoma.
Prevalence and clinicopathological characteristics of lipomatous neurofibromas in neurofibromatosis 1: An investigation of 229 cutaneous neurofibromas and a systematic review of the literature
Authors: Rozza‐de‐Menezes Rafaela Elvira , Brum Carolina de Almeida Ito , Gaglionone Nicolle Cavalcante , de Sousa Almeida Lilian Machado , Andrade‐Losso Raquel Machado , Paiva Brenda Vasconcelos Barboza , Faveret Pedro Leonardo Sanches , da Silva André Vallejo , Siqueira Orlando Hiroshi Kiono , Riccardi Vincent M. , Cunha Karin Soares
Published: June 2018

Background

Lipomatous neurofibroma (Lnf) is a histopathological variant with adipocytes noted among cells of cutaneous neurofibromas. We aimed to investigate the prevalence and clinicopathological features of Lnfs of neurofibromatosis 1 (NF1)‐associated cutaneous neurofibromas and to review the literature systematically. We also evaluated the expression of leptin (a hormone involved in lipid metabolism) in neurofibromas to better understand the pathogenesis of Lnfs.

Methods

A prospective histologic study was conducted on 229 cutaneous neurofibromas from 85 NF1 individuals. Leptin expression was immunohistochemically evaluated in 111 cutaneous neurofibromas. To systematically review the literature, two authors independently performed literature searches without year restriction.

Results

Forty (17.5%) neurofibromas were lipomatous. Lnfs were significantly larger lesions and associated with females. Eighteen (7.9%) of all neurofibromas had multinucleated floret‐like giant cells, and these were associated with Lnfs. All neurofibromas expressed leptin. We systematically reviewed 13 articles. Three large studies investigated Lnfs mainly in sporadic neurofibromas and suggested that 0.3% to 8.0% of tumors (NF1 and sporadic) are Lnfs.

Conclusion

In NF1, Lnfs are common, mainly in larger tumors and women. All cutaneous NF1‐neurofibromas express leptin. It is unknown if the expression of leptin accounts for the lipomatous variant, but it may have a role in the pathogenesis of cutaneous neurofibroma.
Complex patterns of temperature sensitivity, not ecological traits, dictate diverse species responses to climate change
Authors: Schuetz Justin G. , Mills Katherine E. , Allyn Andrew J. , Stamieszkin Karen , Bris Arnault Le , Pershing Andrew J.
Published: July 2018

Despite widespread interest in describing and forecasting the impacts of climate change on species distributions, poor understanding of the climate variables that shape distributions and conflicting perspectives on the role that species traits play in mediating shifts have limited our ability to interpret and project changes in species distributions. Using standardized survey data along the northeast US continental shelf, we assessed the historical exposure and sensitivity of 81 species of marine chordates, arthropods, and molluscs to 24 sea surface temperature (SST) variables in two seasons. By comparing temperature trends in geographies available to species against temperature trends in geographies used by them we were able to identify which variables species track consistently through space and time. Logistic regression analyses were then used to assess whether species traits affected the likelihood of niche tracking while accounting for the season and temporal window in which temperatures were summarized and methodological constraints that might have limited our ability to detect tracking responses. A slight majority of species (52%) clearly shifted their distributions to track at least one temperature variable through space and time. Tracking rates were much lower on a per variable basis (5.1% of 3432 variables), despite widespread exposure to changing temperatures (89.2% of 3432 variables). None of the twelve ecological traits we investigated – including traits related to dispersal ability, ecological specialization, reproductive capacity, and commercial harvest – accounted for differences in tracking responses across species even after accounting for differences in climate exposure. Our results suggest widespread behavioral or physiological flexibility among our study species, or ongoing genetic adaptation to changing temperatures. They also suggest that divergent selection on climate sensitivities of close relatives may limit the utility of ecological traits for predicting distributional responses to future climate change.
Accessibility maps as a tool to predict sampling bias in historical biodiversity occurrence records
Authors: Monsarrat Sophie , Boshoff Andre F. , Kerley Graham I. H.
Published: July 2018

Historical biodiversity occurrence records are often discarded in spatial modeling analyses because of a lack of a method to quantify their sampling bias. Here we propose a new approach for predicting sampling bias in historical written records of occurrence, using a South African example as proof of concept. We modelled and mapped accessibility of the study area as the mean of proximity to freshwater and European settlements. We tested the model's ability to predict the location of historical biodiversity records from a dataset of 2612 large mammal occurrence records collected from historical written sources in South Africa in the period 1497–1920. We investigated temporal, spatial and environmental biases in these historical records and examined if the model prediction and occurrence dataset share similar environmental bias. We find a good agreement between the accessibility map and the distribution of sampling effort in the early historical period in South Africa. Environmental biases in the empirical data are identified, showing a preference for lower maximum temperature of the warmest month, higher mean monthly precipitation, higher net primary productivity and less arid biomes than expected by a uniform use of the study area. We find that the model prediction shares similar environmental bias as the empirical data. Accessibility maps, built with very simple statistical rules and in the absence of empirical data, can thus predict the spatial and environmental biases observed in historical biodiversity occurrence records. We recommend that this approach be used as a tool to estimate sampling bias in small datasets of occurrence and to improve the use of these data in spatial analyses in ecological and conservation studies.
Predation rate and performance of three ladybirds against the green peach aphid Myzus persicae in sweet pepper
Authors: Beltrà Aleixandre , Wäckers Felix L. , Nedvěd Oldřich , Pekas Apostolos
Published: July 2018

Myzus persicae (Sulzer) (Hemiptera: Aphididae) is one of the most common and harmful pest species attacking sweet pepper. Here, we compared the predation rate and performance of Adalia bipunctata (L.), Hippodamia variegata (Goeze), and Scymnus interruptus Goeze (Coleoptera: Coccinellidae) fed on M. persicae infesting sweet pepper. In the laboratory, when offered 150 aphids daily, A. bipunctata was the most voracious species (predation per adult female of 122.7 aphids per 24 h) followed by H. variegata (87.7) and S. interruptus (27.3). When offered 50 aphids, 92% of the S. interruptus larvae developed to adults, 48% of H. variegata, and only 7% of A. bipunctata. In greenhouse experiments, A. bipunctata completely eradicated the aphid population within 2 days following release, whereas H. variegata and S. interruptus initially reduced the aphid population; however, in the long‐term, the infestation was not controlled. Adults of A. bipunctata remained on the plants even in the absence of prey but they laid almost no eggs. Very few adults of H. variegata and S. interruptus were recorded on the plants despite the presence of prey, yet egg laying was observed. Overall, A. bipunctata had an immediate impact on the aphids and is more suitable for curative releases. However, it showed limited potential to establish in the crop. Due to their capacity to complete development with low prey availability, the potential of H. variegata and S. interruptus for preventative releases against aphids in greenhouse crops should be studied further.
Effects of tree species diversity on insect herbivory and leaf defences in Cordia dodecandra
Authors: Rosado‐Sánchez Silvia , Parra‐Tabla Víctor , Betancur‐Ancona David , Moreira Xoaquín , Abdala‐Roberts Luis
Published: July 2018

1. It is broadly accepted that plant diversity influences plant–herbivore interactions, yet few studies have separated damage by different herbivore species and simultaneously tested for effects on herbivory and plant defences to elucidate the mechanisms underlying such effects.

2. This study tested for effects of tree species diversity on leaf damage by beetle larvae and caterpillars on Cordia dodecandra in a diversity experiment, and measured leaf chemical and physical traits to assess whether differences in herbivory underlie changes in plant traits.

3. Four year‐old trees were sampled in 21 × 21‐m plots classified as monocultures of C. dodecandra or mixtures of this species plus three other tree species. Herbivory by beetle larvae and caterpillars was estimated, and we subsequently collected undamaged leaves to quantify total phenolics and condensed tannins, trichome density, and specific leaf area.

4. A significant effect of diversity on herbivory by beetle larvae was found, with mixtures exhibiting an 80% lower mean value than monocultures. By contrast, there was no diversity effect on caterpillar herbivory. Additionally, a positive relationship was found between beetle larvae (but not caterpillar) damage and plant chemical defences, yet there was no effect of diversity on defences. Specific leaf area was higher and trichome density tended to be lower in mixtures than in monocultures, but neither trait was associated with herbivory, and damage did not explain diversity effects on these traits.

5. These findings emphasise the importance of separating diversity effects on different herbivore species and measuring plant traits associated with herbivory to better understand controls of diversity on plant–herbivore interactions.
Diets of endangered silver chub (Macrhybopsis storeriana, Kirtland, 1844) in Lake Erie and implications for recovery
Authors: Kočovský Patrick M.
Published: July 2018

Silver chub (Macrhybopsis storeriana, Kirtland, 1844) is a native Cyprinid in Lake Erie, one of the Laurentian Great Lakes of North America. It is listed as endangered by the US state of New York and Canada, which has a recovery plan, and as special concern by the state of Michigan. Silver chub faces a potential threat to recovery from control efforts for invasive Grass carp (Ctenopharyngodon idella, Valenciennes 1844). Among the knowledge gaps for protection and restoration is current diet data. I describe the diet of silver chub from western Lake Erie in 2014, and I compare it to past studies to assess changes in diet through time. Silver chub captured in bottom trawls May–September 2014 were frozen in the field, and stomach contents were preserved in ethanol. Diet taxa were identified to the lowest practical taxonomic unit, then dried and weighed. Frequency of occurrence in silver chub diets was highest for Hexagenia spp. mayflies (79%). Dreissena spp. and Hexagenia spp. were both 41% of the diet by dry weight. Analysis of δ13C isotopes identified Hexagenia spp. as the primary source of carbon in silver chub. Compared to past studies, Dreissena spp. have mostly replaced Sphaeriidae and Gastropoda in silver chub diets. There also have been seasonal shifts in relative amounts of shelled organisms and Hexagenia spp. This study and past research suggest a functional link between silver chub and Hexagenia spp. abundance. Maintenance and recovery of silver chub may be dependent on maintaining Hexagenia spp. populations.
Alterations in brain microstructure in rats that develop abnormal aggression following peripubertal stress
Authors: Walker Sophie E. , Wood Tobias C. , Cash Diana , Mesquita Michel , Williams Steven C. R. , Sandi Carmen
Published: July 2018

Exposure to early adversity is implicated in the development of aggressive behaviour later in life in some but not all individuals. The reasons for the variability in response to such experiences are not clear but may relate to pre‐existing individual differences that influence their downstream effects. Applying structural magnetic resonance imaging (MRI) to a rat model of abnormal aggression induced by peripubertal stress, we examined whether individual differences in the development of an aggressive phenotype following stress exposure were underpinned by variation in the structure of aggression‐associated, corticolimbic brain regions. We also assessed whether responsiveness of the hypothalamic–pituitary–adrenal axis to stress was associated with neurobehavioural outcome following adversity. A subset of the rats exposed to peripubertal stress developed an aggressive phenotype, while the remaining rats were affected in other behavioural domains, such as increased anxiety‐like behaviours and reduced sociability. Peripubertal stress led to changes in tissue microstructure within prefrontal cortex, amygdala and hippocampal formation only in those individuals displaying an aggressive phenotype. Attenuated glucocorticoid response to stress during juvenility predicted the subsequent development of an aggressive phenotype in peripubertal stress‐exposed rats. Our study establishes a link between peripubertal stress exposure in rats and structural deviations in brain regions linked to abnormal aggression and points towards low glucocorticoid responsiveness to stress as a potential underlying mechanism. We additionally highlight the importance of considering individual differences in behavioural response to stress when determining neurobiological correlates.
A model of the decision‐support scheme for express pest risk analysis using a Bayesian network implemented in Excel
Authors: Holt J. , Leach A. W. , Schrader G.
Published: June 2018

A model was developed to accompany the EPPO decision support scheme for express pest risk analysis (PRA) and provide a calculated overall risk and uncertainty for the PRA and so act as a reference for the judgement of overall risk and uncertainty provided by expert working groups. Implemented in Excel, it is readily accessible to PRA practitioners and offers: (a) a consistent and explained weighting of the different risk factors and a rationale for the way they are combined, (b) a calculated integration of the risk factor distributions to facilitate judgement of overall uncertainty, and (c) an account of the interaction between the rating and the uncertainty score so that, for example, an overall rating of moderate is not necessarily used to reflect uncertainty about assessments in which the risk is neither obviously high nor low. Of the nine published express PRAs examined, the rating and uncertainty predicted by the model were: in agreement with five; differed in both rating and uncertainty in one case; differed in rating only in one case; and differed in uncertainty only in two cases. Possible reasons for these differences were examined and the interpretation of model results to inform assessments is discussed.
Life‐history traits buffer against heat wave effects on predator–prey dynamics in zooplankton
Authors: Zhang Huan , Urrutia‐Cordero Pablo , He Liang , Geng Hong , Chaguaceda Fernando , Xu Jun , Hansson Lars‐Anders
Published: July 2018

In addition to an increase in mean temperature, extreme climatic events, such as heat waves, are predicted to increase in frequency and intensity with climate change, which are likely to affect organism interactions, seasonal succession, and resting stage recruitment patterns in terrestrial as well as in aquatic ecosystems. For example, freshwater zooplankton with different life‐history strategies, such as sexual or parthenogenetic reproduction, may respond differently to increased mean temperatures and rapid temperature fluctuations. Therefore, we conducted a long‐term (18 months) mesocosm experiment where we evaluated the effects of increased mean temperature (4°C) and an identical energy input but delivered through temperature fluctuations, i.e., as heat waves. We show that different rotifer prey species have specific temperature requirements and use limited and species‐specific temperature windows for recruiting from the sediment. On the contrary, co‐occurring predatory cyclopoid copepods recruit from adult or subadult resting stages and are therefore able to respond to short‐term temperature fluctuations. Hence, these different life‐history strategies affect the interactions between cyclopoid copepods and rotifers by reducing the risk of a temporal mismatch in predator–prey dynamics in a climate change scenario. Thus, we conclude that predatory cyclopoid copepods with long generation time are likely to benefit from heat waves since they rapidly “wake up” even at short temperature elevations and thereby suppress fast reproducing prey populations, such as rotifers. In a broader perspective, our findings suggest that differences in life‐history traits will affect predator–prey interactions, and thereby alter community dynamics, in a future climate change scenario.
Community‐ and ecosystem‐level effects of multiple environmental change drivers: Beyond null model testing
Authors: De Laender Frederik
Published: June 2018

Understanding the joint effect of multiple drivers of environmental change is a key scientific challenge. The dominant approach today is to compare observed joint effects with predictions from various types of null models. Drivers are said to combine synergistically (antagonistically) when their observed joint effect is larger (smaller) than that predicted by the null model. Here, I argue that this approach does not promote understanding of effects on important community‐ and ecosystem‐level variables such as biodiversity and ecosystem function. I use ecological theory to show that different mechanisms can lead to the same deviation from a null model's prediction. Inversely, I show that the same mechanism can lead to different deviations from a null model's prediction. These examples illustrate that it is not possible to make strong mechanistic inferences from null models. Next, I present an alternative framework to study such effects. This framework makes a clear distinction between two different kinds of drivers (resource ratio shifts and multiple stressors) and integrates both by incorporating stressor effects into resource uptake theory. I show that this framework can advance understanding because of three reasons. First, it forces formalization of “multiple stressors,” using factors that describe the number and kind of stressors, their selectivity and dynamic behaviour, and the initial trait diversity and tolerance among species. Second, it produces testable predictions on how these factors affect biodiversity and ecosystem function, alone and in combination with resource ratio shifts. Third, it can fail in informative ways. That is, its assumptions are clear, so that different kinds of deviations between predictions and observed effects can guide new experiments and theory improvement. I conclude that this framework will more effectively progress understanding of global change effects on communities and ecosystems than does the current practice of null model testing.
Long‐term decline despite conservation efforts questions Eurasian Stone‐curlew population viability in intensive farmlands
Authors: Gaget Elie , Fay Remi , Augiron Steve , Villers Alexandre , Bretagnolle Vincent
Published: July 2018

Agricultural intensification over the past decades has led to a generalized decline in farmland biodiversity. Farmland birds are particularly exposed to rapid changes in habitat and reduced food resources or availability. Understanding how farmland specialists can be preserved and their populations enhanced are major challenges for this century. Based on a long‐term (19‐year) study of a Eurasian Stone‐curlew Burhinus oedicnemus population, we estimated the demographic parameters, including clutch size, egg volume, hatching success, survival rate and apparent population size. Demographic rates found for this French population were, on average, comparable to those found elsewhere in Europe. However, all demographic parameters showed negative trends, including a dramatic decline in the local population (26% decline over 14 years) and a 10% decline in adult survival rate over 11 years. Such a long‐term decline, despite on‐going conservation efforts, calls into question the overall sustainability of arable Stone‐curlew populations. We infer some of the possible causes of this decline, in particular food shortage, and discuss how this pattern could be reversed through conservation measures applicable at very large spatial scales.
How midwives manage rapid pre‐loading of fluid in women prior to low dose epidurals: A retrospective chart review
Authors: Lindstrom Hannah , Kearney Lauren , Massey Debbie , Godsall Guy , Hogan Emma
Published: July 2018

Aim

To describe contemporary routine practice regarding rapid pre‐loading of intravenous fluid management prior to epidural analgesia during labour and birth.

Background

Midwives are the key health professionals providing care for women before, during and after an epidural in labour. Part of this management involves maternal hydration; however, how midwives assess and manage maternal hydration and fluid management is not well understood. Prior to the administration of a low dose epidural for pain relief a rapid intravenous pre‐loading of between 500‐1000 mls of crystalloid fluids is administered to the pregnant women. Currently, there is limited evidence available to assess if intravenous pre‐loading reduces maternal hypotension and foetal bradycardia. Anecdotal evidence suggests that wide variation in clinical practice in relation to volume of fluid administered, fluid status assessment and clinical documentation occurs.

Design

A retrospective medical health record review, in a regional Australian maternity hospital.

Methods

A retrospective medical health record review chart review from women who received an epidural for pain relief during labour and birth (June–September 2015).

Results

Data from 293 charts were collected, including: maternal factors; blood pressure distributions; maternal fluid status; types, concentration and timing of analgesia loading doses; IV fluid loading volumes; maternal hypotension, foetal outcomes and documentation of fluid balance charts. Wide variation in clinical practice was evident with midwives administering pre‐loading fluid volumes ranging from 250‐1000 ml. Midwifery assessment, documentation and practice pertaining to hydration was inconsistent and lacking.

Conclusion

Management of intravenous fluids during labour is fragmented. Although fluid balance charts are used internationally to assess maternal hydration, documentation of fluid balance status was poor. Multi‐professional collaboration between obstetrics, anaesthetics and midwifery is required to address this wide variation and reach consensus on best practice based on what evidence is currently available.
Patient support during treatment for active tuberculosis and for latent tuberculosis infection: Policies and practices in European low‐incidence countries
Authors: Jansen‐Aaldring Niesje , van de Berg Sarah , van den Hof Susan
Published: July 2018

Aim

To provide an overview of the policies and practices of patient support during treatment for active tuberculosis and for latent tuberculosis infection in European countries with a low incidence of tuberculosis and to identify potential best practices.

Background

Policies, practices and its’ evaluations from similar settings may aid in the development of evidence‐based patient support guidelines.

Design

Descriptive study.

Methods

In June 2016, a survey was conducted among the 24 European low tuberculosis incidence countries (<20 patients per 100,000 population).

Results

Nineteen of the 24 countries approached responded. Most countries (18/19) gave some form of tuberculosis patient support including various treatment supervision options and treatment adherence interventions such as health education, psycho‐emotional and socio‐economic support. Patient support for persons on treatment for latent tuberculosis infection was less widely (9/19) implemented. Patient support guidelines were available in 13 countries, but none of the interventions included had been quantitatively evaluated for their effects on treatment adherence. Potential best practices included appointing a tuberculosis coordinator in charge of organizing patient support; putting a treatment plan meeting with patients, providers and stakeholders in place; supplying direct enablers for marginalized patients; organizing cultural‐sensitive community support; and dispensing pill cases. A lack of resources impeded the provision of patient support, especially for home‐based treatment supervision.

Conclusion

We summarized policies and practices of tuberculosis and latent tuberculosis infection patient support in low tuberculosis incidence European countries. Given the lack of quantitative evaluations, more research is needed to verify the effectiveness of identified potential best practices.
Children and young people with Down syndrome: Their awareness of Down syndrome and developing self‐perceptions
Authors: Deakin Karen , Moore Derek G. , Jahoda Andrew
Published: July 2018

Background

Past research suggests children with Down syndrome often lack awareness of their disability despite the visibility of their condition.

Method

This study used novel tasks to investigate their insight. Twenty‐eight young people with Down syndrome (aged 8–17 years) were recruited, along with control groups of 67 typically developing young people. Three tasks explored the children's awareness of Down syndrome: (a) choice of partner for social activities, (b) sorting photographs and (c) attributing positive or negative descriptors to photographs.

Results

All participants expressed a preference to engage in social activities with typically developing peers. Most participants with Down syndrome identified with the typically developing person. Even though all participants attributed more positive descriptors to the photographs of the typically developing individuals, they remained positive about themselves.

Conclusion

The early awareness of difference shown by young people with Down syndrome suggests this may play an important role in their developing identities.
Community assembly and diversification in a species‐rich radiation of island weevils (Coleoptera: Cratopini)
Authors: Kitson James J. N. , Warren Ben H. , Thébaud Christophe , Strasberg Dominique , Emerson Brent C.
Published: July 2018

Aim

To test a prediction derived from island biogeographical theory that in situ speciation should make an increasingly important contribution to community assembly as islands age. This prediction is tested on estimated biogeographical histories from Mauritius (approximately 9 Myr) and Reunion (approximately 5 Myr). We additionally investigate the evolutionary dynamics of insect flight loss, as the loss of flight in island lineages can influence patterns of diversification.

Location

Mascarene Islands; Southwest Indian Ocean.

Taxon

Weevils.

Methods

Up to five individuals of each taxonomically described species sampled within each sampling site were sequenced for the mitochondrial gene Cytochrome Oxidase II to delimit operational taxonomic units (OTUs). OTUs were further sequenced for the nuclear genes Arginine Kinase, Histone 3 and ribosomal 28s, to reconstruct the phylogenetic history of the group. Timings of colonization and in situ speciation events were estimated with beast2.

Results

Our results support the hypothesis that present‐day species richness on the older island of Mauritius is largely the result of in situ speciation, with few colonization events, of which all but the most basal are recent. In contrast, Reunion presents a more uniform temporal spectrum of colonization times. Flight loss has evolved convergently at least five times, and speciation events associated with flight loss are significantly younger than speciation events that have not resulted in flight loss.

Main conclusions

Patterns of community assembly on the islands of Mauritius and Reunion fit a model where the addition of new species and species turnover is increasingly dominated by in situ speciation as an island community matures. Repeated flight loss indicates selection for flightlessness, with the young age of flightless lineages suggesting higher extinction rates over longer evolutionary time‐scales and little influence on present‐day species richness.
Range shifts in response to past and future climate change: Can climate velocities and species’ dispersal capabilities explain variation in mammalian range shifts?
Authors: Williams J. Eric , Blois Jessica L.
Published: July 2018

Aim

Range shift is a relatively well‐understood response to climate change, but our ability to predict shifts is limited. Two factors that may cause variation in range shifts across species are dispersal ability and varying rates of climate change through time and across space. Here, we assess patterns of range shifts during the late Quaternary and estimate how the velocity of climate change and the dispersal ability of a species affect the magnitude of species range shifts in response to climate change.

Location

North America.

Methods

We hindcast species distribution models for 122 North American mammals to five times over the past 17,000 years and forecast them to two future times given two emissions scenarios. Generalized additive models were constructed to quantify the importance of dispersal ability and the velocity of temperature and precipitation in determining the magnitude of range shift expected for individual species.

Results

Hindcasted and forecasted ranges demonstrate the variety of responses to climate change. In general, species shifted their ranges in a northerly direction (NW, N, NE) regardless of the type of climate change (i.e., warming vs. cooling). The highest rates of range shifts during the past occurred during periods of relatively rapid climate change (Last Glacial Maximum/Bølling‐Allerød and Bølling‐Allerød/Younger Dryas transitions). Rates of range shifts for the future are projected to be significantly higher than any of the past intervals. The velocity of climate change is significantly associated with the magnitude of range shifts during climate transitions that occur over longer time‐scales, while maximum dispersal distance is important during periods of rapid climate change.

Main Conclusions

Our results suggest that both the dispersal ability and the velocity of climate change are significantly associated with species’ range shifts. However, the importance of these two factors is context‐dependent and depends on the interaction of the rate of climate change and the length of time over which the change occurs.
Corporate social responsibility and product quality
Authors: Calveras Aleix , Ganuza Juan‐José
Published: July 2018

We study both theoretically and empirically the relationship between different types of corporate social responsibility (CSR) and a firm's product quality. On the one hand, observable external CSR (e.g., a firm's involvement in a social project) can be used as a signal to unobservable product quality. On the other hand, internal CSR (e.g., human resources practices such as training and labor stability) can improve a firm's labor productivity, specially in firms supplying high quality. We show that CSR may serve as a tool for a firm's product differentiation strategy, finding that both internal and external CSR enhance a firm's product quality. Moreover, this implies the existence of complementarity between internal and external CSR (they mutually reinforce each other) through product quality. We test our theoretical results with data from the hotel industry where we show that hotel establishments with a higher product quality are indeed more likely to be socially responsible, both internally and externally, indicative of the existence of complementarity.
Metformin inhibits visceral allodynia and increased gut permeability induced by stress in rats
Authors: Nozu Tsukasa , Miyagishi Saori , Kumei Shima , Nozu Rintaro , Takakusaki Kaoru , Okumura Toshikatsu
Published: July 2018

Background and Aim

Metformin has been shown to have anti‐cytokine property. Lipopolysaccharide (LPS)‐induced or repeated water avoidance stress (WAS)‐induced visceral allodynia and increased gut permeability were pro‐inflammatory cytokine‐dependent responses, which were considered to be animal models of irritable bowel syndrome (IBS). We hypothesized that metformin improves symptoms in the patients with IBS by attenuating these visceral changes and tested the hypothesis in rats.

Methods

The threshold of the visceromotor response induced by colonic balloon distention was measured. Colonic permeability was determined in vivo by quantifying the absorbed Evans blue for 15 min spectrophotometrically.

Results

Subcutaneously injected LPS (1 mg/kg) reduced the threshold of visceromotor response, and metformin (5–50 mg/kg for 3 days) intraperitoneally attenuated this response in a dose‐dependent manner. Repeated WAS (1 h daily for 3 days) induced visceral allodynia, which was also blocked by metformin. The antinociceptive effect of metformin on the LPS‐induced allodynia was reversed by compound C, an adenosine monophosphate‐activated protein kinase inhibitor or NG‐nitro‐L‐arginine methyl ester, a nitric oxide synthesis inhibitor but not modified by naloxone. Additionally, it was blocked by sulpiride, a dopamine D2 receptor antagonist, but domperidone, a peripheral dopamine D2 receptor antagonist, did not alter it. Metformin also blocked the LPS‐induced or repeated WAS‐induced increased colonic permeability.

Conclusions

Metformin attenuated the visceral allodynia and increased gut permeability in animal IBS models. These actions may be evoked via activation of adenosine monophosphate‐activated protein kinase, nitric oxide, and central dopamine D2 pathways. These results indicate the possibility that metformin can be useful for treating IBS.
Celiac disease gene expression data can be used to classify biopsies along the Marsh score severity scale
Authors: Charlesworth Richard P G , Agnew Linda L , Scott David R , Andronicos Nicholas M
Published: July 2018

Background and Aim

The diagnosis of celiac disease autoimmune pathology relies on the subjective histological assignment of biopsies into Marsh score categories. It is hypothesized that Marsh score categories have unique gene expression signatures. The aims were as follows: first, to develop a celiac disease quantitative reverse transcription–polymerase chain reaction (RT‐PCR) array; second, define gene expression signatures associated with Marsh score categories; and third, develop equations that classify biopsies into Marsh score categories and to monitor the efficacy of patient treatment.

Methods

Gene targets for inclusion in the celiac RT‐PCR (qRT‐PCR) array were identified using systematic analysis of published celiac transcriptomic data. The array was used to assess the gene expression associated with histological changes in duodenal biopsies obtained from adult patients. Finally, Marsh score classification equations were defined using discriminant analysis.

Results

The array contained 87 genes. The expression of 26 genes were significantly (p < 0.06) associated with the discrete Marsh score categories. As the Marsh score pathology of biopsies increased, there was a progression of innate immune gene expression through adaptive Th1‐specific gene expression with a concurrent decrease in intestinal structural gene expression in high Marsh score samples. These 26 genes were used to define classification equations that accounted for 99% of the observed experimental variation and which could classify biopsies into Marsh score categories and monitor patient treatment progression.

Conclusions

This proof‐of‐concept study successfully developed a celiac RT‐PCR array and has provided evidence that discriminant equations defined using gene expression data can objectively and accurately classify duodenal biopsies into Marsh score categories.
Substance use disorders in patients with intellectual disability admitted to psychiatric hospitalisation
Authors: Salavert J. , Clarabuch A. , Fernández‐Gómez M. J. , Barrau V. , Giráldez M. P. , Borràs J.
Published: July 2018

Background

Few studies have looked at the prevalence of substance use disorders (SUD) in people with intellectual disability (ID). The results range between 1% and 6.4% and go up to 20% in people with ID and psychiatric disorders, probably underestimating real prevalence due to several limitations in these studies. ID confers risk for the development of SUD, which in turn will involve negative psychosocial and clinical consequences. We aimed to study the prevalence of SUD in a sample of patients with ID admitted to a brief hospitalisation psychiatric unit, describing them by type and severity and analysing their relationship with clinical, prognostic and access to treatment variables.

Methods

We undertook a descriptive, cross‐sectional and retrospective study by means of a review of clinical histories of all patients with a diagnosis of ID, admitted in a period of 10 years.

Results

Among the final sample of patients included, 52.3% had a mild ID, 40.9% an unspecified ID, 3.4% a moderate ID and another 3.4% a severe ID. More than one third of the sample met criteria for a SUD. The main SUD was cannabis use disorder (25%), followed by alcohol use disorder (22.7%) and cocaine use disorder (13.6%). The use of more than one substance was the most frequent pattern. Cannabis use disorder and cocaine use disorder were overrepresented in the group with mild ID. A greater number of psychiatric admissions was observed for the group with SUD. Specialised mental health services for ID and specialised addiction network facilities were much less involved in the care of these patients that could be expected according to good clinical practice recommendations.

Conclusions

Substance use disorder in patients with ID and mental health disorders admitted to psychiatric hospitalisation are prevalent, which makes this issue an area of interest for future improvements in case identification, proper referring to specialised treatment resources and an increasing research focusing on specific therapeutic approaches.
The combination of ribose and adenine promotes adenosine release and attenuates the intensity and frequency of epileptiform activity in hippocampal slices: Evidence for the rapid depletion of cellular ATP during electrographic seizures
Authors: Hall Jessicka , Frenguelli Bruno G.
Published: July 2018

In addition to being the universal cellular energy source, ATP is the primary reservoir for the neuromodulator adenosine. Consequently, adenosine is produced during ATP‐depleting conditions, such as epileptic seizures, during which adenosine acts as an anticonvulsant to terminate seizure activity and raise the threshold for subsequent seizures. These actions protect neurones from excessive ionic fluxes and hence preserve the remaining cellular content of ATP. We have investigated the consequences of manipulation of intracellular ATP levels on adenosine release and epileptiform activity in hippocampal slices by pre‐incubating slices (3 h) with creatine (1 mM) and the combination of ribose (1 mM) and adenine (50 μM; RibAde). Creatine buffers and protects the concentration of cellular ATP, whereas RibAde restores the reduced cellular ATP in brain slices to near physiological levels. Using electrophysiological recordings and microelectrode biosensors for adenosine, we find that, while having no effect on basal synaptic transmission or paired‐pulse facilitation, pre‐incubation with creatine reduced adenosine release during Mg2+−free/4‐aminopyridine‐induced electrographic seizure activity, whereas RibAde increased adenosine release. This increased release of adenosine was associated with an attenuation of both the intensity and frequency of seizure activity. Given the depletion of ATP after injury to the brain, the propensity for seizures after trauma and the risk of epileptogenesis, therapeutic strategies elevating the cellular reservoir of adenosine may have value in the traumatized brain. Ribose and adenine are both in use in man and thus their combination merits consideration as a potential therapeutic for the acutely injured central nervous system.

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Caregiver experience, health‐related quality of life and life satisfaction among informal caregivers to patients with amyotrophic lateral sclerosis: A cross‐sectional study
Authors: Sandstedt Petter , Littorin Susanne , Cröde Widsell Gunilla , Johansson Sverker , Gottberg Kristina , Ytterberg Charlotte , Olsson Mariann , Widén Holmqvist Lotta , Kierkegaard Marie
Published: July 2018

Aims and objectives

This study set out to describe caregiver experience, health‐related quality of life and life satisfaction among informal caregivers to patients with amyotrophic lateral sclerosis and to explore factors associated with caregivers’ health‐related quality of life and life satisfaction.

Background

Knowledge about factors related to caregivers’ health‐related quality of life and life satisfaction is important for identification of those at risk for ill health and for development of support and care.

Design

A cross‐sectional study.

Methods

Forty‐nine informal caregivers and 49 patients were included. Standardised and study‐specific questionnaires were used for data collection on caregiver experience (Caregiver Reaction Assessment), health‐related quality of life (EuroQol Visual Analogue Scale, SF‐36), life satisfaction (Life Satisfaction Checklist) and caregiver‐ and patient‐related factors. Associations were explored by regression analyses.

Results

Both positive and negative caregiver experience were reported, and health‐related quality of life and life satisfaction were below national reference values. Positive experience was associated with better and negative with worse mental health‐related quality of life. Factors related to informal caregivers (sex, age, living conditions) and patients (anxiety and/or depression) were related to caregivers’ health‐related quality and life satisfaction.

Conclusion

The results indicate the need to consider the individual caregiver's experience when planning services, care and support. It is important to adopt person‐centred care, not only for patients but also for their informal caregivers, as factors related to both parties were associated with the informal caregivers’ health‐related quality of life and life satisfaction.

Relevance to clinical practice

Our study suggests that promoting positive experience and providing services and support to reduce negative aspects of caregiving might be important strategies for healthcare personnel to improve informal caregivers’ health.