bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of Saudi and Canadian children's knowledge of the causes of learning difficulties
Authors: Felimban Huda , Nowicki Elizabeth A. , Dare Lynn , Brown Jason
Published: January 2017

In this comparative study, students from inclusive schools in Canada and Saudi Arabia shared their beliefs about factors associated with learning difficulties. Qualitative data were collected through interviews with 36 Canadian and 62 Saudi elementary students in Grades 5 and 6. Thematic analysis uncovered six themes: lack of knowledge, achievement or academic skills; cognitive and social‐emotional barriers; lack of attention and/or motivation and behavioural issues; home and parental concerns; teacher‐related issues; and physical/sensory disabilities and innate conditions. Although participants from both countries had a general understanding of the factors associated with learning difficulties, Canadian students showed a deeper understanding of cognitive and social‐emotional factors associated with learning difficulties. Educational and research implications are discussed.
Green inclusion: biophilia as a necessity
Authors: Stavrianos Alexandros
Published: January 2017

This article argues that there is a strong link between the pedagogy for inclusion and the pedagogy of environmental education and tries to identify any benefits that could be acquired by pupils when the school system tries to use environmental educational programmes to promote inclusion. The idea of promoting a school yard into a school garden is given as an example. The article suggests that outdoor education experiences can facilitate positive development of self‐esteem, peer to peer socialisation as well as teacher–student relationships and a positive attitude towards school. One might conclude that the rationale behind environmental education has much to offer to all of our pupils.
How can children with mild literacy difficulties be supported at the transition to secondary school? A small‐scale quasi‐experimental study
Authors: Bark Caroline , Brooks Greg
Published: January 2017

There is evidence that pupils with weak literacy skills struggle on transition to secondary school. Many experience a drop in attainment in the summer break between the two. A British government‐funded programme of rigorously designed research on boosting literacy at transition had (by 2015) found only four of 15 interventions evaluated had positive effects. This small‐scale quasi‐experimental study investigated the effectiveness of support for pupils with mild literacy difficulties on transition to secondary school. Thirty‐two pupils in three schools were involved; half received the programme. Pairs were matched on reading, spelling, age and gender. Intervention was designed around the individual needs of each pupil, focusing variously on language skills, writing, reading and spelling. The group receiving the programme made modest gains in spelling, reading efficiency and single word reading. The comparison group lost ground, relatively, in all three areas. The results suggest a promising line for more rigorous investigation.
University foodservices’ potential for providing environmental education to students
Authors: Slobbé Chelsea , Mirosa Miranda , Thomson Carla
Published: January 2017

Aims

University foodservices are potentially well placed to foster environmental education in a non‐classroom setting and so could have the power to benefit communities through producing environmentally literate graduates. Buy‐in from foodservice staff is critical for realising this potential, so understanding what foodservice staff think about their foodservice engaging in the provision of environmental education is essential. The aim of this study was to identify the dominant perspectives held by university foodservice staff about the desirability and realities of fostering environmental education in their workplaces.

Methods

The study design integrated two phases: (i) 36 foodservice staff conducted a card‐sorting activity that revealed four dominant viewpoints; (ii) 60 foodservice staff completed a survey where they identified with one of these viewpoints. The study was conducted in Dunedin, New Zealand.

Results

The four main perspectives were The ‘Believer’, the ‘Relatively Positive Integrator’, the ‘Uncertain Contender’ and the ‘Sceptic’. All of the perspective groups, except for Sceptic, believed environmental education in their workplace was desirable. In the survey, 25% of the 60 participants self‐identified with the Believer narrative, 40% with the Relatively Positive Integrator, 25% with the Uncertain Contender and 10% with the Sceptic. There were no significant differences between factors for sociodemographic characteristics.

Conclusions

A paradigm shift in foodservice framework thinking could unlock the potential university foodservice has to assist universities whose strategic mission is to embed environmental education in both curricular and co‐/extracurricula activities.
A Quality Improvement Initiative to Decrease the Rate of Solitary Blood Cultures in the Emergency Department
Authors: Choi Joseph , Ensafi Sahand , Chartier Lucas Brien , Van Praet Oliver
Published: January 2017

Objectives

Best practice guidelines recommend that at least two sets of blood cultures (BCs) be sent when blood cultures are required. However, high rates of solitary BCs are still common in the emergency department (ED). The aim of this study was to evaluate the efficacy of different quality improvement initiatives aimed at reducing the rate of solitary blood cultures being sent to the laboratory on patients ultimately discharged from our ED.

Methods

This was a multicenter, multiphase, prospective study evaluating a comprehensive education‐based intervention and a second intervention that combined a computerized forcing function (FF) along with a brief education‐based intervention. The results were analyzed using segmented regression analysis, as well as statistical process control charts.

Results

The baseline rate of solitary sets of BCs was 41.1%. The education intervention reduced this rate to 30.3%. The introduction of a FF with a brief educational intervention further reduced the rate to 11.6%. This represents an absolute reduction of 29.5% from baseline (relative reduction of 71.8%). According to segmental regression analyses, the education intervention alone did not produce a statistically significant change when factoring possible background time‐related trends (p = 0.071). However, the FF produced a statistically significant improvement (p < 0.0005), which was maintained for 6 months.

Conclusion

The combination of a brief education‐based intervention and a computerized FF was more effective than education alone in reducing solitary BC collection in our ED in this time series study. FFs can be a powerful tool in modifying behaviors and processes in the clinical setting.
Prenatal Alcohol Consumption Between Conception and Recognition of Pregnancy
Authors: McCormack Clare , Hutchinson Delyse , Burns Lucy , Wilson Judy , Elliott Elizabeth , Allsop Steve , Najman Jake , Jacobs Sue , Rossen Larissa , Olsson Craig , Mattick Richard
Published: January 2017

Background

Current estimates of the rates of alcohol‐exposed pregnancies may underestimate prenatal alcohol exposure if alcohol consumption in early trimester 1, prior to awareness of pregnancy, is not considered. Extant literature describes predictors of alcohol consumption during pregnancy; however, alcohol consumption prior to awareness of pregnancy is a distinct behavior from consumption after becoming aware of pregnancy and thus may be associated with different predictors. The purpose of this study was therefore to examine prevalence and predictors of alcohol consumption by women prior to awareness of their pregnancy, and trajectories of change to alcohol use following pregnancy recognition.

Methods

Pregnant women (n = 1,403) were prospectively recruited from general antenatal clinics of 4 public hospitals in Australian metropolitan areas between 2008 and 2013. Women completed detailed interviews about alcohol use before and after recognition of pregnancy.

Results

Most women (n = 850, 60.6%) drank alcohol between conception and pregnancy recognition. Binge and heavy drinking were more prevalent than low‐level drinking. The proportion of women who drank alcohol reduced to 18.3% (n = 257) after recognition of pregnancy. Of women who drank alcohol, 70.5% ceased drinking, 18.3% reduced consumption, and 11.1% made no reduction following awareness of pregnancy. Socioeconomic status (SES) was the strongest predictor of alcohol use, with drinkers more likely to be of high rather than low SES compared with abstainers (OR = 3.30, p < 0.001). Factors associated with different trajectories (either cessation, reduction, or continuation of drinking) included level of alcohol use prior to pregnancy recognition, age, pregnancy planning, and illicit substance use.

Conclusions

In this sample of relatively high SES women, most women ceased or reduced drinking once aware of their pregnancy. However, the rate of alcohol‐exposed pregnancies was higher than previous estimates when the period prior to pregnancy recognition was taken into account.
Affordable orphan drugs: a role for not‐for‐profit organizations
Authors: Davies Elin H. , Fulton Emma , Brook Daniel , Hughes Dyfrig A.
Published: January 2017

Aims

The success of the Regulation on Orphan Medicinal Products in the European Union is evidenced by the 127 orphan drugs that have had market authorization since 2000. However, the incentives aimed at stimulating research and development have had the unintended consequence of increasing drug cost, resulting in many orphan drugs not being cost‐effective. Orphan drugs command an increasing share of the pharmaceutical market and account for a disproportionate amount of healthcare expenditure. Orphan drug ownership by socially motivated, not‐for‐profit organizations may facilitate access to more affordable orphan drugs, for the benefit of patients and healthcare systems alike. This study aims to describe opportunities for such organizations to become orphan drug Market Authorization Holders.

Methods

We reviewed data on the ownership of EMA designated and approved orphan drugs, identified funding opportunities and business models for not‐for‐profit organizations, and summarised relevant legal and policy documents concerning intellectual property rights and drug regulation.

Results

Using repurposed drugs as a paradigm, this narrative review navigates the regulatory hurdles, describes the legal context and identifies funding opportunities, in a bid to facilitate and encourage not‐for‐profit organizations to lead on the development of affordable orphan drugs.

Conclusions

Although the regulatory steps required to obtain an MA for an orphan drug are numerous and challenging, they are not insurmountable and can be achieved by not‐for‐profit organizations that are socially motivated to reduce the costs of orphan drugs to the payers of healthcare. Opportunities for orphan drug development resulting in affordable products lie mainly with repurposed drugs.
β‐Caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice
Authors: Varga Zoltan V. , Matyas Csaba , Erdelyi Katalin , Cinar Resat , Nieri Daniela , Chicca Andrea , Nemeth Balazs Tamas , Paloczi Janos , Lajtos Tamas , Corey Lukas , Hasko Gyorgy , Gao Bin , Kunos George , Gertsch Jürg , Pacher Pal
Published: January 2017

Background and Aims

β‐Caryophyllene (BCP) is a plant‐derived FDA approved food additive with anti‐inflammatory properties. Some of its beneficial effects in vivo are reported to involve activation of cannabinoid CB2 receptors that are predominantly expressed in immune cells. Here, we evaluated the translational potential of BCP using a well‐established model of chronic and binge alcohol‐induced liver injury.

Methods

In this study, we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real‐time PCR and histology analyses. Serum and hepatic BCP levels were also determined by GC/MS.

Results

Chronic treatment with BCP alleviated the chronic and binge alcohol‐induced liver injury and inflammation by attenuating the pro‐inflammatory phenotypic `M1` switch of Kupffer cells and by decreasing the expression of vascular adhesion molecules intercellular adhesion molecule 1, E‐Selectin and P‐Selectin, as well as the neutrophil infiltration. It also beneficially influenced hepatic metabolic dysregulation (steatosis, protein hyperacetylation and PPAR‐α signalling). These protective effects of BCP against alcohol‐induced liver injury were attenuated in CB2 receptor knockout mice, indicating that the beneficial effects of this natural product in liver injury involve activation of these receptors. Following acute or chronic administration, BCP was detectable both in the serum and liver tissue homogenates but not in the brain.

Conclusions

Given the safety of BCP in humans, this food additive has a high translational potential in treating or preventing hepatic injury associated with oxidative stress, inflammation and steatosis.

Linked Articles

This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
Oncogenic roles of SMARCB1/INI1 and its deficient tumors
Authors: Kohashi Kenichi , Oda Yoshinao
Published: January 2017

SMARCB1/INI1 is one of the core subunit proteins of the ATP‐dependent SWI/SNF chromatin remodeling complex, and is identified as a potent and bona fide tumor suppressor. Interactions have been demonstrated between SMARCB1/INI1 and key proteins in various pathways related to tumor proliferation and progression: the p16‐RB pathway, WNT signaling pathway, sonic hedgehog signaling pathway and Polycomb pathway. Initially, no detectable SMARCB1/INI1 protein expression was found in malignant rhabdoid tumor cells, whereas all other kinds of tumor cells and non‐tumorous tissue showed SMARCB1/INI1 protein expression. Therefore, immunohistochemical testing for the SMARCB1/INI1 antibody has been considered useful in confirming the histologic diagnosis of malignant rhabdoid tumors. However, recently, aberrant expression of SMARCB1/INI1 has been found in various tumors such as epithelioid sarcomas, schwannomatosis, synovial sarcomas, and so on. In addition, it has been reported that aberrant expression can be classified into three patterns: complete loss, mosaic expression and reduced expression. Although the various pathways related to mechanisms of tumorigenesis and tumor proliferation are complexly intertwined, the clarification of these mechanisms may contribute to therapeutic strategies in SMARCB1/INI1‐deficient tumors. In terms of pathological classifications, SMARCB1/INI1‐deficient tumors may be re‐classified by genetic backgrounds.
1‐[(2,3‐Dihydro‐1‐benzofuran‐2‐yl) methyl]piperazines as novel anti‐inflammatory compounds: Synthesis and evaluation on H3R/H4R
Authors: Corrêa Michelle Fidelis , Varela Marina Themoteo , Balbino Aleksandro Martins , Torrecilhas Ana Claudia , Landgraf Richardt Gama , Troncone Lanfranco Ranieri Paolo , Fernandes João Paulo dos Santos
Published: January 2017

The histamine receptors (HRs) are members of G‐protein‐coupled receptor superfamily and traditional targets of huge therapeutic interests. Recently, H3R and H4R have been explored as targets for drug discovery, including in the search for dual‐acting H3R/H4R ligands. The H4R, the most recent histamine receptor, is a promising target for novel anti‐inflammatory agents in several conditions such as asthma and other chronic inflammatory diseases. Due to similarity with previously reported ligands of HRs, a set of 1‐[(2,3‐dihydro‐1‐benzofuran‐2‐yl)methyl]piperazines were synthesized and evaluated in competitive binding assays as H3R/H4R ligands herein. The results showed the compounds presented affinity (Ki) for H3R/H4R in micromolar range, and they are more selective to H3R. All the compounds showed no important cytotoxicity to mammalian cells. The phenyl‐substituted compound LINS01005 has shown the higher affinity of the set for H4R, but no considerable selectivity toward this receptor over H3R. LINS01005 showed interesting anti‐inflammatory activity in murine asthma model, reducing the eosinophil counts in bronchoalveolar lavage fluid, as well as the COX‐2 expression. The presented compounds are valuable prototypes for further improvements to achieve better anti‐inflammatory agents.
Chloride ion transport and overexpression of TMEM16A in a guinea‐pig asthma model
Authors: Kondo M. , Tsuji M. , Hara K. , Arimura K. , Yagi O. , Tagaya E. , Takeyama K. , Tamaoki J.
Published: January 2017

Background

TMEM16A, a Ca‐activated Cl channel, regulates various physiological functions such as mucin secretion. However, the role of TMEM16A in hyper‐secretion in asthma is not fully understood.

Objective

The aim of this study is to evaluate Cl ion transport via TMEM16A and determine the localization of TMEM16A in a guinea‐pig asthma model.

Methods

Guinea‐pigs were sensitized with ovalbumin (OVA) i.p. on Days 1 and 8. On Day 22, we assessed OVA challenge‐induced Cl ion transport in the sensitized tracheas ex vivo in an Ussing chamber, compared with the non‐sensitized tracheas. We then examined the effect of T16Ainh‐A01, a TMEM16A inhibitor, on the increase in Cl ion transport. The tracheal epithelium was immunostained with an anti‐TMEM16A antibody. Epithelial cells from guinea‐pig tracheas were cultured at the air–liquid interface in the presence of IL‐13 for in vitro study. We studied the effect of TMEM16A inhibitors on Ca‐dependent agonist, uridine triphosphate (UTP)‐induced increases in Cl ion transport in the cultured cells. The cells were immunostained with an anti‐TMEM16A antibody, an anti‐MUC5AC antibody and an anti‐α‐tubulin antibody.

Results

OVA challenge induced an increase in short circuit current within 1 min in the OVA‐sensitized tracheas but not in the non‐sensitized tracheas, which was inhibited by pretreatment of T16Ainh‐A01. Sensitized tracheas showed goblet cell metaplasia with more positive TMEM16A immunostaining, particularly in the apical portion compared with the non‐sensitized tracheas. The in vitro UTP‐induced increase in Cl ion transport was strongly inhibited by pretreatment with T16Ainh‐A01, benzbromarone, and niflumic acid. TMEM16A was positively immunostained at the apical portion and in the MUC5AC‐positive area in IL‐13‐induced goblet cell metaplasia.

Conclusions

Antigen challenge and Ca‐dependent agonist treatment increased Cl ion transport via the overexpression of TMEM16A in goblet cell metaplasia in a guinea‐pig asthma model. TMEM16A inhibitors may be useful for the treatment of hyper‐secretion in asthma.
Assessment of biological, psychological and adherence factors in the prediction of step‐down treatment for patients with well‐controlled asthma
Authors: Saito N. , Kamata A. , Itoga M. , Tamaki M. , Kayaba H. , Ritz T.
Published: January 2017

Background and Objective

Inhaled corticosteroids (ICS) and inhaled corticosteroids combined with long‐acting beta2‐agonist (ICS/LABA) are standard treatments for asthma. However, factors that might help reduce medication in well‐controlled asthma are unknown. We classified problems of asthma patients into biological, psychological and adherence factors, and investigated factors associated with the indication and failure of a medication step‐down treatment.

Methods

Two hundred twenty two well‐controlled asthma patients receiving ICS or ICS/LABA were assessed for physical and psychiatric problems and followed up for one year from adjustment of their treatment step. Factor B was defined as a presence of chronic upper airway complications. Factor P was defined as presence of psychiatric complications such as sleep disorder, depression, anxiety and somatoform disorders. Factor A was defined as poor adherence to ICS or ICS/LABA inhaler of 75% or less. Success in step‐down treatment was defined as maintenance of well‐controlled status for over one year after step‐down.

Results

Factor B was the most important single negative predictive factor for indication for step‐down treatment (Odds ratio; 0.19). Factor A increased the risk of failure to maintain step‐down treatment most significantly by 23‐fold, and factor B increased it by 11‐fold. The combination of factors B and A increased failure by 24‐fold, factors P and A by 21‐fold, all three factors by 36‐fold. Factor P only interacted with the other factors to reduce chances of stepping down, but did not constitute a problem factor when present alone.

Conclusion and Clinical Relevance

The evaluation of biological, psychological and adherence problems may lead to a more proactive and targeted approach to step‐down treatment for patients with well‐controlled asthma.
Maternal psychiatric symptoms during pregnancy and risk of childhood atopic diseases
Authors: Elbert N. J. , Duijts L. , den Dekker H. T. , de Jong N. W. , Nijsten T. E. C. , Jaddoe V. W. V. , de Jongste J. C. , van Wijk R. Gerth , Tiemeier H. , Pasmans S. G. M. A.
Published: January 2017

Background

Maternal psychiatric symptoms during pregnancy might affect the developing immune system and subsequent risk of childhood atopic diseases.

Objective

Our aim was to examine the associations of maternal psychiatric symptoms during pregnancy with allergic sensitization, allergy and eczema in children until age 10 years.

Methods

This study among 5205 children was performed in a population‐based prospective cohort from foetal life onwards. We assessed maternal and paternal psychiatric symptoms (overall, depressive, anxiety) during pregnancy and at 36 months after delivery, and maternal psychiatric symptoms at 2 and 6 months after delivery using the Brief Symptom Inventory. Inhalant and food allergic sensitization were measured by skin prick tests, and physician‐diagnosed inhalant and food allergy or eczema by questionnaires from birth until age 10 years. We used multivariate logistic regression, multinomial logistic regression or generalized estimating equation models where appropriate.

Results

We observed no association of maternal psychiatric symptoms during pregnancy with allergic sensitization. Maternal overall psychiatric, depressive and anxiety symptoms during pregnancy were associated with an increased risk of inhalant allergy only (adjusted odds ratio (95% confidence interval) 1.96 (1.44, 2.65), 1.58 (1.25, 1.98) and 1.61 (1.27, 2.03), respectively, per 1‐unit increase). Maternal overall psychiatric and anxiety symptoms during pregnancy were associated with an increased risk of eczema (1.21 (1.05, 1.39) and 1.15 (1.02, 1.29), respectively, per 1‐unit increase). Effect estimates did not materially change when maternal psychiatric symptoms after delivery, or paternal psychiatric symptoms during pregnancy and after delivery were taken into account.

Conclusions and Clinical Relevance

Maternal psychiatric symptoms during pregnancy were associated with increased risks of childhood inhalant allergy and eczema, independent of maternal psychiatric symptoms after delivery and of paternal psychiatric symptoms.
The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?
Authors: Carty F , Mahon B P , English K
Published: January 2017

Mesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date; recently, however, a number of studies have shown that the therapeutic effect of MSC requires the presence of macrophages. It is timely to review the mechanisms and manner by which MSC modulate macrophage populations in order to design more effective MSC therapies and clinical studies. A complex cross-talk exists through which MSC and macrophages communicate, a communication that is not controlled exclusively by MSC. Here, we examine the evidence that suggests that MSC not only respond to inflammatory macrophages and adjust their secretome accordingly, but also that macrophages respond to encounters with MSC, creating a feedback loop which contributes to the immune regulation observed following MSC therapy. Future studies examining the effects of MSC on macrophages should consider the antagonistic role that macrophages play in this exchange.
Accuracy of magnetic resonance enterography in the preoperative assessment of patients with Crohn's disease of the small bowel
Authors: Pous‐Serrano S. , Frasson M. , Palasí Giménez R. , Sanchez‐Jordá G. , Pamies‐Guilabert J. , Llavador Ros M. , Nos Mateu P. , Garcia‐Granero E.
Published: January 2017

Aim

To assess the accuracy of magnetic resonance enterography in predicting the extension, location and characteristics of the small bowel segments affected by Crohn's disease.

Method

This is a prospective study including a consecutive series of 38 patients with Crohn's disease of the small bowel who underwent surgery at a specialized colorectal unit of a tertiary hospital. Preoperative magnetic resonance enterography was performed in all patients, following a homogeneous protocol, within the 3 months prior to surgery. A thorough exploration of the small bowel was performed during the surgical procedure; calibration spheres were used according to the discretion of the surgeon. The accuracy of magnetic resonance enterography in detecting areas affected by Crohn's disease in the small bowel was assessed. The findings of magnetic resonance enterography were compared with surgical and pathological findings.

Results

Thirty‐eight patients with 81 lesions were included in the study. During surgery, 12 lesions (14.8%) that were not described on magnetic resonance enterography were found. Seven of these were detected exclusively by the use of calibration spheres, passing unnoticed at surgical exploration. Magnetic resonance enterography had 90% accuracy in detecting the location of the stenosis (75.0% sensitivity, 95.7% specificity). Magnetic resonance enterography did not precisely diagnose the presence of an inflammatory phlegmon (accuracy 46.2%), but it was more accurate in detecting abscesses or fistulas (accuracy 89.9% and 98.6%, respectively).

Conclusion

Magnetic resonance enterography is a useful tool in the preoperative assessment of patients with Crohn's disease. However, a thorough intra‐operative exploration of the entire small bowel is still necessary.
Integrated treatment options for male perpetrators of intimate partner violence
Authors: Crane Cory A. , Easton Caroline J.
Published: January 2017

Issues

Male‐to‐female intimate partner violence remains a worldwide public health issue with adverse physical and psychological consequences for victims, perpetrators and children. Personality disorders, addiction, trauma and mood symptoms are established risk factors for intimate partner violence perpetration and factor prominently into a recovery‐oriented treatment approach.

Approach

We reviewed the partner violence literature for detailed reports of traditional as well as innovative, integrated treatment approaches. Empirically based recommendations for intervention programs and the policies that guide intervention efforts are offered.

Key Findings

Nascent research suggests that integrated treatment models utilising a holistic approach to account for psychological comorbidity and interventions that involve a motivational interviewing component appear promising in terms of significantly improving intimate partner violence treatment compliance and reducing subsequent acts of physical partner violence. Further, methodologically rigorous research is required to fully assess the benefits of traditional and integrated treatment options.

Implications

We have advanced several recommendations, including the development of and exclusive reliance upon empirically supported treatments, conducting a thorough risk and needs assessment of the offender and the immediate family to facilitate appropriate treatment referrals, integrating content to foster the offender's internal motivation to change maladaptive behaviours, and attempting to minimise offender treatment burdens through the strategic use of integrated treatment models.

Conclusions

Intimate partner violence is a complicated and nuanced problem that is perpetrated by a heterogeneous population and requires greater variability in integrated treatment options. [Crane CA, Easton CJ. Integrated treatment options for male perpetrators of intimate partner violence. Drug Alcohol Rev 2017;36:24–33]
Rwandan “home grown initiatives”: Illustrating inherent contradictions of the democratic developmental state
Authors: Hasselskog Malin
Published: January 2017

The 21st‐century developmental state is envisaged as implying democratic participation. Rwanda both explicitly aspires to follow the developmental state example and eloquently ascribes to far‐reaching participatory ideals, and a number of development programmes, “home grown initiatives,” have been launched, allegedly reviving traditional participatory practices. Based on original material, this article analyzes local experiences of the participation entailed in some of these programmes. In the conclusion, the poor practice of participation reported is found to point to inherent contradiction of the idea of a democratic and participatory version of the developmental state.
The evolutionary origination of a novel expression pattern through an extreme heterochronic shift
Authors: Pham Thomas , Day Stephanie M. , Glassford William J. , Williams Thomas M. , Rebeiz Mark
Published: January 2017

The evolutionary origins of morphological structures are thought to often depend upon the redeployment of old genes into new developmental settings. Although many examples of cis‐regulatory divergence have shown how pre‐existing patterns of gene expression have been altered, only a small number of case studies have traced the origins of cis‐regulatory elements that drive new expression domains. Here, we elucidate the evolutionary history of a novel expression pattern of the yellow gene within the Zaprionus genus of fruit flies. We observed a unique pattern of yellow transcript accumulation in the wing disc during the third larval instar, a stage that precedes its typical expression pattern associated with cuticular melanization by about a week. The region of the Zaprionus wing disc that expresses yellow subsequently develops into a portion of the thorax, a tissue for which yellow expression has been reported for several fruit fly species. Tests of GFP reporter transgenes containing the Zaprionus yellow regulatory region revealed that the wing disc pattern arose by changes in the cis‐regulatory region of yellow. Moreover, the wing disc enhancer activity of yellow depends upon a short conserved sequence with ancestral thoracic functions, suggesting that the pupal thorax regulatory sequence was genetically reprogrammed to drive expression that commences much earlier during development. These results highlight how novel domains of gene expression may arise by extreme shifts in timing during the origins of novel traits.
Mortality on fruit in citrus orchards caused by naturally occurring enemies of red scale Aonidiella aurantii: relation to spatial distribution of patch density and season
Authors: Dao H.T. , Meats A. , Beattie G.A.C. , Spooner‐Hart R.
Published: January 2017

The efficacy of biological control agents depends on the amount of mortality they impose on pests in the field. Quantifying their impact on a pest is critical for guiding decision‐making in its management. Here, we quantify the relation of population levels of natural unmanipulated populations of a pest to mortality rates imposed by naturally occurring enemies. Mortality beyond first instar caused by natural enemies of Aonidiella aurantii (Maskell) (Hemiptera: Diaspididae) on fruit was studied in four unsprayed citrus orchards in a warm temperate coastal environment in New South Wales, Australia, over approximately three pest generations in the course of a year. The percentage of hosts on fruit suffering parasitism and predation was usually independent of host density. There was no consistent evidence that one parasitoid influenced another, nor that parasitism and predation rates were related. At the orchard scale, it was apparent that parasitism and predation over a time series were related to current or previous host numbers and could become high enough in relation to fecundity rates to cause pest numbers to decline. Temporal feedback to density could be causing the pest populations to fluctuate between limits at economically sustainable levels given additional mortality of the first instars due to expected rates of dispersal and subsequent pre‐ and post‐settlement failures.
Style length variation in male and female figs: development, inheritance, and control of pollinator oviposition
Authors: Ghana Salah , Suleman Nazia , Compton Stephen G.
Published: January 2017

Fig trees (Ficusspp.,Moraceae) depend on female fig wasps to transport their pollen and as a reward provide nutrition for pollinator fig wasp larvae. Most pollinators are host specific, but natural plant hybrids occur if atypical hosts are pollinated. Female fig wasps lay their eggs into ovaries of female flowers in receptive figs by inserting their ovipositors through the styles, and relative style and ovipositor lengths are believed to largely determine their ability to oviposit. In dioecious fig trees, flowers in receptive male figs have short styles and support larval development, whereas flowers in receptive female figs have long styles and only develop into seeds. Using the dioecious fig tree speciesFicus montanaBurm. f. andFicus asperifoliaMiq., we recorded the comparative ontogeny of style lengths to determine whether style growth in the two sexes is coordinated with the attraction of pollinators, and how maximum style lengths relate to the ovipositor lengths of their pollinators. F1 hybrids between these species produce viable seeds, but no pollinator offspring. We examined style lengths in F1s and backcrosses, relative to those of their parents, and whether coordination of style growth with pollinator attraction is disrupted. The ovipositor ofKradibia tentacularis(Grandi) (Hymenoptera:Agaonidae), the pollinator ofF. montana, could reach some of the ovaries in female figs, but fails to lay eggs there. Styles in male F1 figs were intermediate in length between those of the two parents, but in female F1 figs styles grew longer than in either parent. Maximum style lengths in F1s were partially decoupled from receptivity, especially in female figs. Our results illustrate how timing of stigmal growth is coordinated with pollinator attraction, and that this coordination can be disrupted in hybrid individuals.
Behavioural flexibility does not prevent numerical declines of harvester ants under intense livestock grazing
Authors: POL RODRIGO G. , VARGAS GABRIELA A. , MARONE LUIS
Published: January 2017

1. Human‐induced rapid environmental change may decrease food resources and create unfavourable conditions for native species. Organisms showing a flexible foraging behaviour can exploit novel or alternative foods and are more likely to persist, whereas less flexible organisms might suffer starvation and numerical reductions.

2. This study assessed whether declines in the quality and availability of seeds prompted by grazing provoke behavioural and numerical responses in Pogonomyrmex mendozanus ants, and aimed to test whether behavioural flexibility buffers habitat degradation and prevents numerical declines.

3. Heavy grazing caused seed reductions, especially of the highly consumed and preferred grass seeds, and triggered two kinds of ant responses. Ants expanded their diet by incorporating a greater proportion of non‐seed items, and they reduced foraging activity. As a consequence, the rate of food intake per colony lessened, particularly that of carbohydrate‐rich seeds like grass seeds. Colony density under heavy grazing also fell.

4. Habitat degradation triggered a cascade of mechanisms that starts with a decrease in the seed resources and continues with changes in ant behaviour. However, behavioural responses were insufficient to prevent ant numerical declines. The results of this study suggest that the reduction in the colony density under habitat degradation was provoked by ant nutritional deficit and starvation, and predict a deterioration in body condition, colony performance and reproduction of ants, which deserve further assessment.
Addition of nitrogen enhances stability of soil organic matter in a temperate forest
Authors: Chen Z. J. , Geng S. C. , Zhang J. H. , Setälä H. , Gu Y. , Wang F. , Zhang X. , Wang X. X. , Han S. J.
Published: January 2017

Physicochemical protection of soil carbon provided by soil aggregates is critical to carbon (C) sequestration in terrestrial ecosystems. However, the stability of soil organic matter (SOM) in terrestrial ecosystems in response to atmospheric nitrogen (N) deposition is unclear. In this study, N was added to a forest soil dominated by deciduous trees on Changbai Mountain, China, at three different rates (0, 25 and 50 kg N ha−1 year−1) from 2007 to 2012. Its effect on C content and stabilization was evaluated by soil fractionation and stable isotope (δ13C) analyses. The results showed that large macroaggregates (2–8 mm) decreased and small macroaggregates (0.25–2 mm) increased with increasing rates of N addition, whereas soil C content remained unchanged. Irrespective of the N treatments, the C content of soil organic matter (SOM) fractions differed significantly between large and small macroaggregates, which suggests that the size of aggregate classes regulates C content in the SOM fractions. A slight increase in the C content of microaggregates within macroaggregates (Mm) and that of silt and clay fractions was recorded with the addition of N at 50 kg N ha−1 year−1. This increase also occurred in the silt and clay fraction within microaggregates (Intra‐SC). Unprotected C (comprising the free light fraction (Free‐LF) and coarse particulate organic matter (CPOM)) accounted for 18.9% only of the total C and decreased in response to the addition of N. The δ13C signature and C/N ratios obtained for SOM fractions showed that newly formed C was transferred from POM to Intra‐SC. Overall, our results suggested that long‐term addition of N might promote stabilization of C by increasing small macro‐ and micro‐aggregation within macroaggregates in temperate forest soil.

Highlights

Investigated stability of soil organic matter in response to long‐term N addition in a deciduous forest.

Physicochemical protection of soil organic matter by aggregates changed after N addition.

Soil organic carbon in microaggregates within macroaggregates increased with N addition.

Long‐term N addition might promote C stabilization in temperate forest soil.
Shedding light on interictal epileptic spikes: An in vivo study using fast optical signal and electrocorticography
Authors: Manoochehri Mana , Mahmoudzadeh Mahdi , Osharina Victoria , Wallois Fabrice
Published: January 2017

Objective

Interictal epileptic spikes (IESs), apart from being a key marker of epileptic neuronal networks, constitute a nice model of the widespread endogenous phenomenon of neuronal hypersynchronization. Many questions concerning the mechanisms that drive neurons to hypersynchronize remain unresolved, but synaptic as well as nonsynaptic events are likely to be involved. In this study, changes in optical properties of neural tissues were observed in rats with penicillin‐inducedIESusing fast optical signal (FOS) concomitantly with electrocorticography (ECoG).

Methods

In this study, near‐infrared optical imaging was used withECoG to investigate variations in the optical properties of cortical tissue directly associated with neuronal activity in 15 rats.FOSchanges correspond to variations of scattered light from neuronal tissue when neurons are activated. To independently evaluate our method, a control experiment on somatosensory was designed and applied to seven different rats. Time‐frequency analysis was also used to track variations of (de)synchronization concomitantly with changes in optical signals duringIES.

Results

FOSresponses revealed that changes in optical signals occurred 320 msec before to 370 msec after theIESpeak. These changes started before any changes inECoG signal. In addition, time‐frequency domain electrocorticography revealed an alternating decrease‐increase‐decrease in theECoG spectral power (pointing to desynchronization‐synchronization‐desynchronization), which occurred concomitantly with an increase‐decrease‐increase in relative optical signal during theIES. These results suggest a relationship between (de)synchronization and optical changes.

Significance

These changes in the neuronal environment aroundIESs raise new questions about the mechanisms that induce changes in optical properties of neural tissues before theIES, which may provide suitable conditions for neuronal synchronization duringIESs.FOS‐ECoG constitutes a multimodal approach and opens new avenues to study the mechanisms of neuronal synchronization in the pathologic brain, which has clinical implications, at least in epilepsy.
A simple method for equine kinematic gait event detection
Authors: Holt D. , St George L. B. , Clayton H. M. , Hobbs S. J.
Published: January 2017

Background

Previous studies have validated methods for determining kinematic gait events using threshold‐based techniques. However, a simple method that can be successfully applied to walk, trot and canter is yet to be identified.

Objectives

To develop a simple kinematic method to identify the timing of hoof contact (hoof‐on), peak vertical force and lift off (hoof‐off), which can be applied in walk, trot and canter.

Study design

In vivo method authentication study.

Methods

Horses (n = 3) were ridden in walk, trot and canter down a runway on which four force plates were arranged linearly. Three‐dimensional forces were recorded at a sampling rate of 960 Hz and were synchronised with a 10‐camera motion analysis system sampling at 120 Hz. Events identified from vertical ground reaction force (GRFz) data were hoof‐on (GRFz>50N), peak vertical force (GRFzpeak) and hoof‐off (GRFz<50N). Kinematic identification of hoof‐on and hoof‐off events was based on sagittal planar angles of the fore‐ and hindlimbs. Peak metacarpophalangeal (MCP)/metatarsophalangeal (MTP) joint extension was used to assess the time of GRFzpeak. The accuracy (mean) and precision (s.d.) of time differences between kinetic and kinematic events were calculated for fore‐ and hindlimbs at each gait.

Results

Hoof‐off was determined with better accuracy (range: −3.94 to 8.33 ms) and precision (range: 5.43–11.39 ms) than hoof‐on across all gaits. Peak MCP angle (range: 5.83–19.65 ms) was a more precise representation of GRFzpeak than peak MTP angle (range: 11.49–67.75 ms).

Main limitations

The sample size was small and therefore further validation is required. The proposed method was tested on a single surface.

Conclusions

This study proposes a simple kinematic method of detecting hoof‐on, hoof‐off and GRFzpeak at walk, trot and canter. Further work should focus on validating the methodology in a larger number of horses and should extend the method for use on surfaces with varying levels of compliance.
CD4+TCRγδ+FoxP3+ cells: An unidentified population of immunosuppressive cells towards disease progression leprosy patients
Authors: Tarique Mohd , Naqvi Raza A. , Ali Riyasat , Khanna Neena , Rao Donthamshetty Nageswara
Published: January 2017

This study, for the first time, reveals the role of M. leprae‐specific CD4+TCRγδ+FoxP3+ cells in the progression and pathogenesis of leprosy. Co‐culture with CD4+CD25− cells suggested the immunosuppressive nature of CD4+TCRγδ+ cells in dose‐dependent manner. Isolation of CD4+TCRγδ+ cells from leprosy patients and then culture in presence of M. leprae cell wall antigens (MLCwA) along with TGF β, IPP and IL‐2 suggested that these cells are M. leprae specific. TGF‐β‐mediated SMAD3 signalling was turned out to be major factor towards the expression of FoxP3 in these cells. SMAD3 silencing during induction of these cells barely showed the induction of FoxP3. High density of SMAD3 binding at TGFβRII in CD4+TCRγδ+FoxP3+ furthermore suggested the TGF‐β‐directed SMAD3 signalling in these cells. Taken together the above data, we can conclude that CD4+TCRγδ+FoxP3+ cells possess the potential to track the severity of the disease in leprosy patients.
Cell cycle‐tailored targeting of metastatic melanoma: Challenges and opportunities
Authors: Haass Nikolas K. , Gabrielli Brian
Published: January 2017

The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato‐oncology from the “bad guy” to the “poster child” in oncology. Current targeted therapies are effective, although here is a clear need to develop combination therapies to delay the onset of resistance. Many antimelanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase‐specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle‐mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell subpopulations of a heterogeneous tumor, one drug effective in a particular subpopulation should not negatively impact on the other drug targeting another subpopulation. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves. We propose that cell cycle‐tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real‐time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches.
Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment
Authors: Raaby Line , Rosada Cecilia , Langkilde Ane , Lauridsen Kristina Lystlund , Vinter Hanne , Ommen Pernille , Kjellerup Rasmus Boye , Johansen Claus , Iversen Lars
Published: January 2017

TNFα‐, IL‐23‐ and IL‐17‐targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin, the presence of Langerhans cells (LCs) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNFα and IL‐23/IL‐17 on the presence of LC in the skin during treatment. Therefore, psoriatic skin was investigated before and after 4 days of adalimumab or ustekinumab treatment. Furthermore, TNFα and IL‐17A stimulation was investigated in an ex vivo model of epidermis and dermis from healthy normal skin kept in cultures at an air‐liquid interphase for 4 days. In a gene array analysis, we found that the two LC markers, CD1a and CD207, were among the most up‐ or downregulated genes in psoriatic skin after anti‐TNFα therapy. Validation showed that both mRNA expression and protein level followed the same pattern and became significantly upregulated after 4 days of treatment. No changes were seen after ustekinumab treatment. In the ex vivo skin model, a decrease in the CD1a level was seen after TNFα stimulation and it was caused by LC migration from epidermis. No response in LC migration was seen after IL‐17A stimulation. Taken together, we demonstrated that changes in the LC level in epidermis precede the histological and clinical changes during adalimumab treatment in psoriatic skin. Furthermore, TNFα plays a prominent role in orchestrating LC migration in the skin. This seems not to be the true for the IL‐23/IL‐17A pathway.