bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing effectiveness of nurture groups in Northern Scotland
Authors: Shaver Isabel , McClatchey Kirstie
Published: September 2013

The aim of this small‐scale study was to assess the effectiveness of nurture groups in Northern Scotland. Data were collected from children (N = 19) and staff (N = 5) from three nurture groups. Pre‐ and post‐nurture group Boxall Profile information was also assessed for 33 children across two of the nurture groups. Analysis of the Boxall Profiles found that nurture group children had made significant gains. The majority of children reported that they feel happy and enjoy attending the nurture groups. Nurture group staff reported improvements in the children, and that parents are positive about the nurture groups. However, staff did report a number of challenges that the nurture group face. Overall, this study contributes to the evidence that nurture groups can be an effective intervention for improving social, emotional and behavioural outcomes for children.
Motivational strategies to enhance effective learning in teaching struggling students
Authors: Wery Jessica , Thomson Margareta Maria
Published: September 2013

The challenges presented by students who struggle to connect with curriculum learning in school constitute an issue that confronts education systems worldwide. This article reviews ways in which such students can be encouraged to engage more positively in their own learning, a process that benefits both the child and the whole school community. In this article a range of strategies to do this is proposed, based on a set of theoretical considerations.
A ‘blank cheque'? Portuguese Second World War sterling balances, 1940–73
Authors: de Paiva Abreu Marcelo
Published: September 2013

The British effort in the Second World War required massive external financing which depended on Lend‐Lease and the accumulation of sterling balances. Indebtedness in sterling balances corresponded to almost 38 per cent of this total at the end of the war. Portuguese sterling balances, although a small share of the total, were important because of pre‐emptive purchases, especially of wolfram, and because of the ‘gold clause’ which was to be applied to outstanding balances. Portugal's willingness to finance British purchases contrasts with the requirement of German payments in goods or cash for their purchases in Portugal. The settlement of Portuguese sterling balances in August 1945 was singular as it preceded the Anglo‐American settlement of December 1945 which had important consequences for sterling balance holders, as the US insisted that the US$3.75 billion loan should not be used to settle British war debts. Postwar settlement of British debt through a long‐term loan from Portugal to Britain contrasts with settlements that involved the sale of British assets. Salazar's concerns about the postwar international position of Portugal, the Portuguese Empire, and the survival of the Portuguese regime are relevant in explaining his pro‐British stance during and after the war.
The Weaknesses of Civic Territorial Organizations: Civic Engagement and Homeowners Associations in Urban China
Authors: Fu Qiang , Lin Nan
Published: September 2013

China's massive transformation in urban governance, which is characterized by breaking the link between workplace and residence and consolidating state territorial agencies at the grassroots level, has profound implications for urban residents. While community building is employed as a deliberate (top‐down) approach to restore a governable urban society, the establishment, development and problems of bottom‐up civic territorial organizations — homeowners associations — are garnering increased attention from academia. Based on field research conducted in Guangzhou, Shenzhen and Meizhou in Guangdong Province from 2009 to 2011, we show that civic engagement, a necessary condition for the development of homeowners associations, is inadequate across urban communities. To understand why, we identified and analyzed three elements — lack of awareness of partitioned property ownership, the hidden costs of civic engagement and deficiency in social capital — as factors that impede civic engagement across urban communities. These elements also provide yardsticks for scholars to evaluate why, whether and how homeowners (dis‐)engage from neighborhood affairs.
Oligotyping: differentiating between closely related microbial taxa using 16S rRNA gene data
Authors: Eren A. Murat , Maignien Loïs , Sul Woo Jun , Murphy Leslie G. , Grim Sharon L. , Morrison Hilary G. , Sogin Mitchell L.
Published: September 2013

Bacteria comprise the most diverse domain of life on Earth, where they occupy nearly every possible ecological niche and play key roles in biological and chemical processes. Studying the composition and ecology of bacterial ecosystems and understanding their function are of prime importance. High‐throughput sequencing technologies enable nearly comprehensive descriptions of bacterial diversity through 16S ribosomal RNA gene amplicons. Analyses of these communities generally rely upon taxonomic assignments through reference data bases or clustering approaches using de facto sequence similarity thresholds to identify operational taxonomic units. However, these methods often fail to resolve ecologically meaningful differences between closely related organisms in complex microbial data sets.

In this paper, we describe oligotyping, a novel supervised computational method that allows researchers to investigate the diversity of closely related but distinct bacterial organisms in final operational taxonomic units identified in environmental data sets through 16S ribosomal RNA gene data by the canonical approaches.

Our analysis of two data sets from two different environments demonstrates the capacity of oligotyping at discriminating distinct microbial populations of ecological importance.

Oligotyping can resolve the distribution of closely related organisms across environments and unveil previously overlooked ecological patterns for microbial communities. The URL http://oligotyping.org offers an open‐source software pipeline for oligotyping.
Genetic diversity of legume yellow mosaic begomoviruses in Indonesia and Vietnam
Authors: Tsai W.S. , Shih S.L. , Rauf A. , Safitri R. , Hidayati N. , Huyen B.T.T. , Kenyon L.
Published: September 2013

High incidences of yellow mosaic symptoms were observed in soybean and yard‐long bean crops in Indonesia in 2009 and in mungbean crops in Vietnam in 2011. All five soybean and 20 yard‐long bean samples from Java, Indonesia, and 15 mungbean samples from Vietnam with symptoms tested positive for begomovirus infection by polymerase chain reaction (PCR) with primer pair PAL1v1978B/PAR1c715H. On the basis of collection location and the nucleotide sequence comparisons of the 1.5 kb begomoviral DNA‐A components amplified, a subset of samples comprising two soybean and six yard‐long bean isolates from Indonesia and five mungbean isolates from Vietnam were taken forward for more detailed examination. Sequence comparison and phylogenetic analysis of the full‐length sequences of all Indonesian and Vietnam isolates alongside other legume‐infecting begomoviruses revealed that all the isolates from Indonesia were Mungbean yellow mosaic India virus (MYMIV) strain‐A, and all from Vietnam were Mungbean yellow mosaic virus (MYMV) strain‐B. To the best of our knowledge, this is the first identification of MYMIV and MYMV associated with yellow mosaic of legumes in Indonesia and Vietnam, respectively. The epidemiological implications and potential consequences of the emergence of legume‐infecting begomoviruses on legume production in these areas of Southeast Asia are discussed.
Seed yield, head characteristics and oil content in sunflower varieties as influenced by seeds from single and multiple headed plants under humid tropical conditions
Authors: Olowe V.I. , Folarin O.M. , Adeniregun O.O. , Atayese M.O. , Adekunle Y.A.
Published: September 2013

Field trials were conducted during 2004 and 2005 to determine the effect of sowing seeds from plants with multiple heads and seeds from single headed plants of sunflower on seed yield, head characteristics and oil content of three widely grown open pollinated varieties (Funtua, Record and Isaanka) in the humid forest—savanna transition zone which is outside the current growing areas with a view to improving stability and sunflower productivity in this region. Seeds from multiple headed plants produced plants that flowered and matured 2–3 days later than plants from single headed plants. Apart from days to flowering in 2004, number of days to maturity and plant height were affected independently by variety and seed source factors. However, the seeds from single headed plants produced plants that recorded significantly (P < 0.01) higher head weight, head diameter, achene weight and number per head than plants from seeds of plants with multiple heads. Seed source had little effect on sunflower seed yield and oil content. However, Funtua produced significantly (P < 0.05) high seed yield (1956.0 kg ha−1 ± 76.06) when seeds from plants with multiple heads were sown, while Isaanka recorded comparatively high seed yield from seeds of plants from either multiple (1221.0 kg ha−1 ± 165.90) or single heads (1388.0 kg ha−1 ± 135.84) and Record (1201.0 kg ha−1 ± 96.97) when seeds from single headed plants were sown. Therefore, it is recommended that prospective sunflower growers who wish to cultivate Isaanka, can sow seeds from either the multiple or single head and preferably the multiple head for Funtua, and single head for Record.
Pre‐hospital critical care by anaesthesiologist‐staffed pre‐hospital services in Scandinavia: a prospective population‐based study
Authors: KRÜGER A. J. , LOSSIUS H. M. , MIKKELSEN S. , KUROLA J. , CASTRÉN M. , SKOGVOLL E.
Published: September 2013

Background

All Scandinavian countries provide anaesthesiologist‐staffed pre‐hospital services. Little is known of the incidence of critical illness or injury attended by these services. We aimed to investigate anaesthesiologist‐staffed pre‐hospital services in Scandinavia with special emphasis on incidence and severity.

Methods

This population‐based, prospective study recorded activity in 16 anaesthesiologist‐staffed pre‐hospital services in Denmark, Finland, Norway and Sweden serving half of the Scandinavian population. We calculated population incidence of medical conditions, and the proportion of patients with severely deranged vital signs and/or receiving advanced therapy.

Results

Four thousand two hundred thirty‐six alarm calls were recorded during 4 weeks. Two thousand two hundred fity‐six alarms resulted in a patient encounter. The population incidence varied from 74.9 missions per 10,000 person‐years (Denmark), followed by Finland with 14.6, Norway with 11, and Sweden with 5. Medical aetiology was most frequent (14.9 missions per 10,000 person‐years, 95% CI: 14.2–15.8). Trauma was second (5.6 missions per 10,000 person‐years, 95%CI: 5.12–6.09). Twenty‐three per cent of patients had severely deranged vital functions, and advanced emergency medical procedures were performed in every four to twelve encounters (Denmark 8%, Sweden 15%, Norway 23%, and Finland 25%). The probability that the patient was physiologically deranged, received advanced medication, or procedure was 35%. Critical illness or injury occured at a rate of 25–30 per 10,000 person‐years.

Conclusions

The incidence of pre‐hospital anaesthesiologist patient encounters in Scandinavia varies. Medical aetiology is most frequent. Almost one‐quarter of patients presents with deranged vital functions requiring emergency measures. The Scandinavian pre‐hospital population incidence of critical illness and injury is 25–30 per 10,000 person‐years.
A novel mGluR5 antagonist, MFZ 10‐7, inhibits cocaine‐taking and cocaine‐seeking behavior in rats
Authors: Keck Thomas M. , Zou Mu‐Fa , Bi Guo‐Hua , Zhang Hai‐Ying , Wang Xiao‐Fei , Yang Hong‐Ju , Srivastava Ratika , Gardner Eliot L. , Xi Zheng‐Xiong , Newman Amy Hauck
Published: September 2013

Pre‐clinical studies suggest that negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5), including 2‐methyl‐6‐(phenylethynyl)pyridine (MPEP), 3‐[(2‐methyl‐1,3‐thiazol‐4‐yl)ethynyl]pyridine (MTEP) and fenobam are highly effective in attenuating drug‐taking and drug‐seeking behaviors. However, both MPEP and MTEP have no translational potential for use in humans because of their off‐target effects and short half‐lives. Here, we report that 3‐fluoro‐5‐[(6‐methylpyridin‐2‐yl)ethynyl]benzonitrile (MFZ 10‐7), a novel mGluR5 NAM, is more potent and selective than MPEP, MTEP and fenobam in both in vitro binding and functional assays. Similar to MTEP, intraperitoneal administration of MFZ 10‐7 inhibited intravenous cocaine self‐administration, cocaine‐induced reinstatement of drug‐seeking behavior and cocaine‐associated cue‐induced cocaine‐seeking behavior in rats. Although MFZ 10‐7 and MTEP lowered the rate of oral sucrose self‐administration, they did not alter total sucrose intake. Further, MFZ 10‐7 appeared to be more potent than MTEP in inducing downward shifts in the cocaine dose–response curve, but less effective than MTEP in attenuating sucrose‐induced reinstatement of sucrose‐seeking behavior. MFZ 10‐7 and MTEP had no effect on basal locomotor behavior. These findings not only provide additional evidence supporting an important role for mGluR5 in cocaine reward and addiction, but also introduce a new tool for both in vitro and in vivo investigations with which to further characterize this role.
Sexual selection and genital evolution
Authors: Simmons Leigh W
Published: September 2013

Male genitalia show patterns of divergent evolution, and sexual selection is recognised as being responsible for this taxonomically widespread phenomenon. Much of the empirical support for the sexual selection hypothesis comes from studies of insects. Here, I synthesise the literature on insect genital evolution, and use this synthesis to address the debate over the mechanisms of selection most likely to explain observed patterns of macroevolutionary divergence in genital morphology. Studies of seven insect orders provide evidence that non‐intromittent genitalia are subject to sexual selection through their effects on mating success, while intromittent genitalia are subject to selection through their effects on fertilisation success. However, studies that use quantitative methods to analyse the form of selection are necessary to identify the mechanisms of sexual selection involved. Phylogenetic analyses from diverse taxonomic groups confirm that divergence in male genital morphology can be predicted from variation in the opportunity for sexual selection. Much debate revolves around the importance of female choice and sexual conflict in the evolution of male genitalia, the resolution of which lies in economic studies of mating interactions and in recognising sexual selection as a continuum between male competition, sexual conflict and female choice. The species isolating lock‐and‐key hypothesis is frequently dismissed as unimportant in genital evolution because in part of a perceived lack of variation in female genitalia across species. Increasingly, however, studies report species‐specific variation in female genital morphology and its coevolutionary divergence with male genital morphology. Contemporary views recognise a continuum between female choice that enforces species isolation and female choice that targets variation in male quality within populations, placing lock‐and‐key processes into the realm of sexual selection. Distinguishing between species‐isolating and directional forms of female choice will require studies that examine both the tempo and mode of divergence, both within and among species.
Tolerogenic CX3CR1+ B cells suppress food allergy‐induced intestinal inflammation in mice
Authors: Liu Z.‐Q. , Wu Y. , Song J.‐P. , Liu X. , Liu Z. , Zheng P.‐Y. , Yang P.‐C.
Published: September 2013

Background

B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet.

Objective

This study aims to investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy‐induced intestinal inflammation in mice.

Methods

The intestinal mucosa‐derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs.

Results

A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)‐β and carried integrin alpha v beta 6 (αvβ6). Exposure to recombinant αvβ6 and anti‐IgM antibody induced naive B cells to differentiate into the TGF‐β‐producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy‐induced intestinal Th2 pattern inflammation in mice.

Conclusions

CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy‐related Th2 pattern inflammation in mice.
Teenage pregnancies in the European Union in the context of legislation and youth sexual and reproductive health services
Authors: Part Kai , Moreau Caroline , Donati Serena , Gissler Mika , Fronteira Inês , Karro Helle ,   the REPROSTAT group
Published: September 2013

Objective

To study cross‐country and regional variations and trends in reported teenage pregnancies in the context of legislation and youth sexual and reproductive health (SRH) services in Europe.

Design

Data were collected on teenage live births and induced abortions, abortion legislation and youth SRH services.

Setting

Population‐based statistics from the European Union (EU) member states.

Population

Fifteen‐ to nineteen‐year‐old female teenagers.

Methods

Detailed statistical information for each member state about teenage live births, induced abortions, abortion legislation and youth SRH services were compiled relying on national and international data sources.

Main outcome measures

The annual reported pregnancies per 1000 women aged 15–19 years.

Results

Teenage pregnancy rates have declined since 2001, although progress has been uneven across regions and countries. Eastern Europe has a higher average teenage pregnancy rate (41.7/1000) than Northern (30.7/1000), Western (18.2/1000) and Southern Europe (17.6/1000). While data on teenage live births are available across Europe, data on teenage abortions are unavailable or incomplete in more than one‐third of EU countries. Reported teenage pregnancy rates are generally lower for countries where parental consent for abortion is not required, youth SRH services are available in all areas and contraceptives are subsidized for all minors, compared with countries where these conditions are not met.

Conclusions

The collection of standardized teenage pregnancy statistics is critically needed in the EU. The remarkable variability in teenage pregnancy rates across the EU is likely to be explained, among other factors, by varying access to abortion and youth SRH services.
Employees' Political Skill and Job Performance: An Inverted U‐Shaped Relation?
Authors: Zettler Ingo , Lang Jonas W.B.
Published: September 2013

During the past decade, the construct of political skill has attracted a lot of attention. In particular, its relation to job performance has been examined. With regard to this link, it is typically proposed that political skill affects job performance in a positive linear manner. However, in this article it is suggested that intermediate levels of employees' political skill yield the highest job performance, implying that this association is in fact represented by an inverted U‐shape. Findings from two field studies (N1 = 178, N2 = 115 employee‐supervisor‐colleague triads) that incorporated different sample characteristics (early career employees, established employees), job performance dimensions (overall, task, contextual, and adaptive performance), and rating sources (supervisors and colleagues) supported this idea. Across different analyses, employees with intermediate levels of political skill received higher job performance ratings compared to those with lower and higher levels, respectively. In addition, the nature of the relationships between employees and their raters was found to moderate this curvilinear effect. Specifically, besides the fact that employees who had close working relationships with their raters generally received higher job performance ratings, the decreases in the job performance ratings of employees high in political skill were less pronounced when they had close relationships.
Evolution of Urban–rural Living Standards Inequality in Thailand: 1990–2006
Authors: Fang Zheng , Sakellariou Chris
Published: September 2013

The present study examines the developments in urban–rural living standard inequality in Thailand from 1990 to 2006 using a methodology that allows for the identification of individual contributors to changes in inequality. We also propose a method to analyze the changes over time in urban–rural living standards. We find that the urban–rural gap in living standards in Thailand has narrowed substantially since the early 1990s, both at the mean and especially for households in the upper part of the expenditure distribution; however, the narrowing of the gap at the bottom of the expenditure distribution has been negligible. The study also identifies the main individual contributors to changes over time in living standards between urban and rural areas in Thailand.
Enter the Dragon: Have Imports from China Hurt Wages in Manufacturing?
Authors: Posso Alberto
Published: September 2013

While it is often argued that imports from China are depressing manufacturing wages in recipient countries, this has never been tested using cross‐country data. This article investigates the effect of increased import penetration from China on the wages of workers (total, skilled and unskilled) in the manufacturing sector of 100 economies from 1976 to 2008. The econometric analysis finds no evidence suggesting that import penetration of manufactured goods from China has a statistically significant effect on real manufacturing wages (skilled, unskilled and total) in either developed or developing economies. This may be because Chinese exports are too heterogeneous to strongly affect any particular industry in recipient economies or because foreign consumers are differentiating products made in China from those made locally based on country and brand loyalty and preconceived notions of quality.
Relationships of native trees with grasses in a temperate, semi‐arid sandy ecosystem of northern China
Authors: Yang Hongxiao , Chu Jianmin , Lu Qi , Gao Ting
Published: September 2013

Question

Afforestation is a controversial method for restoring semi‐arid sandy ecosystems to control desertification. We studied how native elm trees (Ulmus pumila L.) interact with grasses in the semi‐arid sandy ecosystem of the Otindag, and how the trees should be arranged to promote ecological restoration.

Location

Otindag Sandy Land, Inner Mongolia, northern China.

Methods

Using 40 adult elms, we investigated and compared root depths of the native trees with those of neighbouring grasses. The shallowest elm roots and the deepest grass roots were analysed. Using four singleton elms, we also examined how soil moisture in the different soil layers (0–10, 10–20, 20–30 and 30–40 cm) and grass biomass density changed with distance from the corresponding tree trunks in four directions within 19 m.

Results

On average, the shallowest elm roots were 17.6 cm deep at 1 m from the elm trunks, and 24.5 cm at 3 m from the elm trunks, whereas the deepest grass roots were 14 cm deep at 1 m from the trunks, and 16.3 cm deep at 3 m from the trunks. The moisture content in the 0–20 cm layers decreased with distance from 1 to 19 m from the singleton elms, but increased along the same distance gradient in the 20–40 cm layers. Grass biomass density decreased along the distance gradient, and a logistic model fits this tendency well, which indicates that the grass biomass density levels off at distances of >ca. 9 m.

Conclusions

Given the vertical divergence of roots and the horizontal pattern of soil moisture, the adult native trees do not compete for much moisture with grasses. The adult native trees have the potential to facilitate the growth and biomass accumulation of nearby grasses. In the semi‐arid sandy ecosystem of the Otindag, native elms can be planted for ecological restoration at intervals of up to 18 m.
Why the Extractive Industry Should Support Mandatory Transparency: A Shared Value Approach
Authors: Topal Julien , Toledano Perrine
Published: September 2013

The Transparency Amendment, included in the Dodd‐Frank Wall Street Reform and Consumer Protection Act, can be an important tool in curtailing the resource curse that so heavily burdens resource‐rich developing countries by shedding light on opaque payments between the extractive sector and host countries. From the get‐go, however, extractive industry companies have fiercely opposed the new mandatory disclosure requirements as set out in this regulation. The corporate opposition is for the largest part motivated by the fear of a competitive disadvantage that derives from the fact that the amendment is housed with the Securities and Exchange Commission (SEC) and thus only holds jurisdiction over those that report to the SEC. Although on the one hand watering down these corporate fears, this article draws on the “shared value approach” and empirical evidence to argue that there is a business case for transparency. This refreshing take on transparency regulation invites corporate leaders to reassess their current oppositional stance and to embrace new initiatives like the Transparency Amendment and to take a proactive stance in building a convincing global regulatory system of transparency.
Structural insights into the arms race between host and virus along RNA silencing pathways in Arabidopsis thaliana
Authors: Guo Wei , Liew Jia Yee , Yuan Y. Adam
Published: September 2013

ABSTRACT

RNA silencing refers to a conserved sequence‐specific gene‐regulation mechanism mediated by small RNA molecules. In plants, microRNA (miRNA) and small interfering RNA (siRNA) represent two major types of small RNA molecules which play pivotal roles in plant developmental control and antiviral defences. To escape these plant defences, plant viruses have encoded a vast array of viral suppressors of RNA silencing (VSRs) to attack the host antiviral silencing pathway by interfering with small RNA processing, RNA‐induced silencing complex (RISC) assembly, viral mRNA cleavage etc. Transgenic plants expressing distinct VSRs often show developmental aberrations that resemble the phenotype of miRNA‐deficient mutants, implying a potential intrinsic link between VSRs and the miRNA pathway (at least in Arabidopsis thaliana) even though their pathogenic mechanisms remain largely unknown. In this review, we summarise our current structural understandings of the arms race between the host and virus along the RNA silencing pathway in A. thaliana by focusing on several important ribonucleoprotein (RNP) structures involved in RNA silencing and unique structural features adopted by VSRs.
Family Context, Mexican‐Origin Adolescent Mothers' Parenting Knowledge, and Children's Subsequent Developmental Outcomes
Authors: Jahromi Laudan B. , Guimond Amy B. , Umaña‐Taylor Adriana J. , Updegraff Kimberly A. , Toomey Russell B.
Published: September 2013

This study examined parenting knowledge among Mexican‐origin adolescent mothers (N = 191; Mage = 16.26 years), family contextual factors associated with adolescents' parenting knowledge, and toddlers' (Mage = 2.01 years) subsequent developmental outcomes. Data came from home interviews and direct child assessments. Adolescents both underestimated and overestimated children's developmental timing, and showed differences in their knowledge of specific developmental domains. Instrumental support from mother figures was positively linked to adolescents' knowledge accuracy, whereas emotional support was negatively related to adolescents' knowledge confidence. Furthermore, whereas mother figures' autonomy granting was positively linked to knowledge confidence, psychological control was associated with less accurate adolescent parenting knowledge. Toddlers of adolescents with more accurate knowledge showed positive developmental functioning. Intervention implications are discussed.
Evaluation of an oral health promotion program at the time of birth on dental caries in 5‐year‐old children in Vorarlberg, Austria
Authors: Wagner Y. , Greiner S. , Heinrich‐Weltzien R.
Published: September 2013

Objectives

The aim of this study was to evaluate the effect of an early oral health promotion program (OHPP) on oral health of 5‐year‐old children in Austria by providing new mothers with dental health counseling.

Methods

Qualified dental health educators visited all mothers at time after birth in regional hospitals in Vorarlberg and counseled them regarding the oral health of their children as a one‐off intervention. Mothers were given comprehensive oral hygiene instructions for their children and themselves (daily use of fluoride toothpaste, restoration of own caries lesions), which included practical tooth brush training and dietary counseling by the use of brief motivational interviewing and anticipatory guidance approaches. After 5 years, a case–cohort study was conducted to evaluate the program with annual dental check‐ups of 471 children and a parent survey. Dental caries was scored using WHO diagnostic criteria at dentine level without radiography. To compare oral health parameters (dmfs/dmft, care index), children were allocated to intervention and control group and matched on basis of age, sex, ethnicity, and socio‐economic status (SES) and analyzed statistically.

Results

Children whose mothers participated in the OHPP showed significantly lower caries prevalence and experience (33.2%; 3.2 ± 7.4 d3–4mfs/1.5 ± 2.5 d3–4mft) than children whose mothers did not participate (42.6%; 5.2 ± 6.4 d3–4mfs/2.4 ± 4.1 d3–4mft). Bivariate analysis showed that ethnicity, SES, age at which toothbrushing started, supervision of toothbrushing, use of fluoride salt, and use of fluoride toothpaste were significantly related to d3–4mft.

Conclusions

The OHPP was an effective community‐based preventive approach for improving oral health in preschool children.
Monoclonal antibodies in treatment of multiple sclerosis
Authors: Rommer P S , Dudesek A , Stüve O , Zettl UK
Published: September 2013

Monoclonal antibodies (mAbs) are used as therapeutics in a number of disciplines in medicine, such as oncology, rheumatology, gastroenterology, dermatology and transplant rejection prevention. Since the introduction and reintroduction of the anti-alpha4-integrin mAb natalizumab in 2004 and 2006, mAbs have gained relevance in the treatment of multiple sclerosis (MS). At present, numerous mAbs have been tested in clinical trials in relapsing–remitting MS, and in progressive forms of MS. One of the agents that might soon be approved for very active forms of relapsing–remitting MS is alemtuzumab, a humanized mAb against CD52. This review provides insights into clinical studies with the mAbs natalizumab, alemtuzumab, daclizumab, rituximab, ocrelizumab and ofatumumab.
Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases
Authors: Fallerini C. , Dosa L. , Tita R. , Del Prete D. , Feriozzi S. , Gai G. , Clementi M. , La Manna A. , Miglietti N. , Mancini R. , Mandrile G. , Ghiggeri G.M. , Piaggio G. , Brancati F. , Diano L. , Frate E. , Pinciaroli A.R. , Giani M. , Castorina P. , Bresin E. , Giachino D. , De Marchi M. , Mari F. , Bruttini M. , Renieri A. , Ariani F.
Published: September 2013

The mode of inheritance of Alport syndrome (ATS) has long been controversial. In 1927, the disease was hypothesized as a dominant condition in which males were more severely affected than females. In 1990, it was considered an X‐linked (XL) semidominant condition, due to COL4A5 mutations. Later on, a rare autosomal recessive (AR) form due to COL4A3/COL4A4 mutations was identified. An autosomal dominant (AD) form was testified more recently by the description of some large pedigrees but the real existence of this form is still questioned by many and its exact prevalence is unknown. The introduction of next generation sequencing (NGS) allowed us to perform an unbiased simultaneous COL4A3‐COL4A4‐COL4A5 analysis in 87 Italian families (273 individuals) with clinical suspicion of ATS. In 48 of them (55%), a mutation in one of the three genes was identified: the inheritance was XL semidominant in 65%, recessive in 4% and most interestingly AD in 31% (15 families). The AD form must therefore be seriously taken into account in all pedigrees with affected individuals in each generation. Furthermore, a high frequency of mutations (>50%) was shown in patients with only 1 or 2 clinical criteria, suggesting NGS as first‐level analysis in cases with a clinical suspicion of ATS.
Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause
Authors: Petit F. , Escande F. , Jourdain A.S. , Porchet N. , Amiel J. , Doray B. , Delrue M.A. , Flori E. , Kim C.A. , Marlin S. , Robertson S.P. , Manouvrier‐Hanu S. , Holder‐Espinasse M.
Published: September 2013

Nager syndrome belongs to the group of acrofacial dysostosis, which are characterized by the association of craniofacial and limb malformations. Recently, exome sequencing studies identified the SF3B4 gene as the cause of this condition in most patients. SF3B4 encodes a highly conserved protein implicated in mRNA splicing and bone morphogenic protein (BMP) signaling. We performed SF3B4 sequencing in 14 families (18 patients) whose features were suggestive of Nager syndrome and found nine mutations predicted to result in loss‐of‐function. SF3B4 is the major gene responsible for autosomal dominant Nager syndrome. All mutations reported predict null alleles, therefore precluding genotype–phenotype correlations. Most mutation‐negative patients were phenotypically indistinguishable from patients with mutations, suggesting genetic heterogeneity.
Autism assessment in children with optic nerve hypoplasia and other vision impairments
Authors: Williams Marian E , Fink Cassandra , Zamora Irina , Borchert Mark
Published: September 2013

Aim

This study examined the utility of standard autism diagnostic measures in nine children (aged 5–9y) with severe vision impairment and a range of social and language functioning.

Method

The Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI‐R) were systematically modified and used to assess symptoms of autism in children with vision less than or equal to 20/800, the majority of whom had optic nerve hypoplasia. The results of the assessments, including analysis of symptom patterns, were compared with expert autism diagnoses.

Results

Modified autism measures demonstrated good agreement with clinical diagnoses. Symptoms found to be most and least reliable in discriminating autism from behaviors common to most children with congenital vision impairment are described. Comparisons of current behavior with parent‐reported behaviors from a younger age suggested that some symptoms of autism in very young children who are congenitally blind may improve with age.

Interpretation

TheADOSandADI‐R are useful for clinical assessment and for advancing research efforts to understand autism symptoms in children with vision impairment. However, some autistic symptoms in very young children may change over time, and developmental changes should be closely monitored.
The accommodative process in children with cerebral palsy: different strategies to obtain clear vision at short distance
Authors: Pansell Tony , Hellgren Kerstin , Jacobson Lena , Brautaset Rune , Tedroff Kristina
Published: September 2013

Aim

Accommodation is the ability of the eye to change focus in order to maintain a sharp image of objects at various distances. The accommodative process is largely unknown in children and requires new assessment techniques. The aim of the study was to investigate this process in children with and without cerebral palsy (CP).

Method

In a descriptive case–control study, children with CP (n=15; nine females, six males; median age 14y) and 21 typically developing children (11 females, 10 males; median age 12y) underwent standard ophthalmological examination and examination by the PowerRefractor. Six of the children had spastic bilateral CP, five had spastic unilateral CP, and four had dyskinetic CP. The children's Gross Motor Function Classification System (GMFCS) levels were as follows: level I, seven children; level II, two children; level III, three children; and level IV, three children. The PowerRefractor measures accommodation in response to minus lens stimuli. Continuous measurements of refraction/accommodation, eye position, and pupil size are obtained. The Kruskal–Wallis analysis of variance (ANOVA) and Mann–Whitney U test were used for between‐group analysis (α=0.05), and Friedman ANOVA was used for within‐group analysis.

Results

The stimuli–response gain (input/output) was approximately 80% in typical children inducing a focusing error (0.2–0.5D) increasing with minus lens power. Children with CP accommodated significantly less (gain: ~30%; p<0.001), inducing a larger focusing error (1.1–1.7D) increasing with minus lens power. The accommodative response was slower and more variable in children with CP. The pupil response did not mirror the accommodative response.

Interpretation

Children with CP exhibit problems in generating an appropriate accommodative response. This can affect everyday living and reading skills.
Exploring causal hypotheses: breaking with long‐standing research traditions
Authors: La Bastide‐Van Gemert Sacha , van den Heuvel Edwin
Published: September 2013

This commentary is on the original article by Faebo Larsen et al. on pages 1016–1022 of this issue.
Macrophages control innate inflammation
Authors: Akira S. , Misawa T. , Satoh T. , Saitoh T.
Published: September 2013

Macrophages play a critical role in the pathogenesis of metabolic diseases including gout and type 2 diabetes. The Nod‐like receptor (NLR) family, pyrin domain containing 3 (NLRP3) forms the inflammasome with apoptosis‐associated speck‐like protein containing a CARD (ASC), the adaptor protein, and mediates inflammatory responses by macrophages. By compound screening, we found that tubulin polymerization inhibitors suppress NLRP3 inflammasome activation. NLRP3 inflammasome inducers reduce the NAD+ level to inactivate the α‐tubulin deacetylase Sirtuin 2, resulting in accumulation of acetylated α‐tubulin. Acetylated α‐tubulin mediates mitochondrial transport and subsequent proximity of ASC on mitochondria to NLRP3 on the endoplasmic reticulum. Thus, microtubule‐driven transport of mitochondria is required for NLRP3 inflammasome activation. Macrophages are comprised of two subsets, M1 (inflammatory) and M2 (anti‐inflammatory). Trib1 is an adaptor protein involved in protein degradation of immune‐related transcription factors. We found that Trib1 is critical for the differentiation of F4/80+MR+ tissue‐resident M2‐like macrophages. Mice lacking Trib1 in haematopoietic cells show severe lipodystrophy owing to increased lipolysis, even on a normal diet. In response to a high‐fat diet, the mice show hypertriglyceridaemia and insulin resistance, together with increased proinflammatory cytokine production. Thus, Trib1 is critical for adipose tissue maintenance and suppression of metabolic disorders by controlling the differentiation of tissue‐resident M2‐like macrophages.
Role of pancreatic β‐cell death and inflammation in diabetes
Authors: Quan W. , Jo E.‐K. , Lee M.‐S.
Published: September 2013

Apoptosis of pancreatic β‐cells is the final step in the development of type 1 diabetes (T1D), leading to critically diminished β‐cell mass and contributing to the onset of hyperglycaemia. The spontaneous apoptosis of pancreatic β‐cells during pancreas ontogeny also induces cell death‐associated inflammation, stimulates antigen‐presenting cells and sensitizes naïve diabetogenic T cells. The role of pancreatic β‐cell death in type 2 diabetes (T2D) is less clear. In the preclinical period of T2D, hyperinsulinaemia and β‐cell hyperplasia develop to compensate for insulin resistance, which is clearly seen in animal models of T2D. For the development of overt T2D, relative insulin deficiency is critical in addition to insulin resistance. Insulin deficiency could be due to β‐cell dysfunction and/or decreased β‐cell mass. Pancreatic β‐cell apoptosis due to lipid injury (lipoapoptosis), endoplasmic reticulum (ER) stress or JNK activation could contribute to the decreased β‐cell mass in T2D. Activation of inflammasomes by lipid injury, ER stress, human islet amyloid polypeptide, hyperglycaemia or autophagy insufficiency could also lead to β‐cell death or dysfunction. Thus, β‐cell death and cell death‐associated inflammation through innate immune receptors could be important in both T1D and T2D.
The immune cells in adipose tissue
Authors: Ferrante A. W.
Published: September 2013

Although the pathological role of the immune system in several metabolic disorders, including type 1 diabetes mellitus (T1DM) and Addison's disease, has long been recognized and studied, only in the last decade has it become apparent that the immune system plays a broad and more subtle role in local and systemic metabolism. It is now apparent that the immune system monitors and responds to specific metabolic cues in both pathologic and non‐pathologic settings through a set of processes dubbed immunometabolism. Expansion of adipose tissue mass, activation of lipolysis, eating a high fat diet and even non‐shivering thermogenesis all lead to the recruitment and activation of immune cells in key metabolic tissues. The responses are complex and not completely defined, and indeed, as is typical of rapidly evolving research areas, there are some conflicting reports, especially related to the metabolic consequences of manipulation of immune function. However, what is clear is the consensus that metabolic processes, especially obesity and obesity‐related complications, activate both the innate and adaptive arms of the immune system. Canonical immune processes consist of discrete steps: surveillance, recognition, effector action and resolution. Over the last decade evidence for each part of the immune response has been found at the intersection of the immune system with metabolism. Although evidence for immune surveillance and modulation of metabolism has been found in the liver, muscle, hypothalamus and pancreas, immune cell function has been most intensively studied and best understood in adipose tissue where studies continue to provide insights into the intersection of the metabolic and immune systems. Here we review the modulation of immune cell populations in adipose tissue and discuss regulatory processes implicated in controlling the interface between metabolism and immunologic function.
Small‐molecule inhibition of inflammatory β‐cell death
Authors: Lundh M. , Scully S. S. , Mandrup‐Poulsen T. , Wagner B. K.
Published: September 2013

With the worldwide increase in diabetes prevalence there is a pressing unmet need for novel antidiabetic therapies. Insufficient insulin production due to impaired β‐cell function and apoptotic reduction of β‐cell mass is a common denominator in the pathogenesis of diabetes. Current treatments are directed at improving insulin sensitivity, and stimulating insulin secretion or replacing the hormone, but do not target progressive apoptotic β‐cell loss. Here we review the current development of small‐molecule inhibitors designed to rescue β‐cells from apoptosis. Several distinct classes of small molecules have been identified that protect β‐cells from inflammatory, oxidative and/or metabolically induced apoptosis. Although none of these have yet reached the clinic, β‐cell protective small molecules alone or in combination with current therapies provide exciting opportunities for the development of novel treatments for diabetes.
The targeting of β‐cells by T lymphocytes in human type 1 diabetes: clinical perspectives
Authors: Luce S. , Briet C. , Bécourt C. , Lemonnier F. , Boitard C.
Published: September 2013

This review focuses on genes that control β‐cell targeting in autoimmune, type 1‐dependent, diabetes (T1D) and on insulin as the major autoantigen recognized by T lymphocytes throughout the disease process. T1D associates with multiple gene variants. Beyond genes that predispose to general failure of immune tolerance to self, loci identified by the analysis of crosses between non‐obese diabetic (NOD) and conventional mouse strains harbour genes that control β‐cell targeting or the deviation of autoimmunity towards other tissues. We report here the role of genes encoding co‐activation molecules involved in the activation of T lymphocytes, ICOS and ICOS ligand (B7RP1). NOD mice which are deficient in either of these two molecules are protected from diabetes, but instead develop a neuromuscular autoimmune disease. We also report the characterization in humans of T lymphocytes that are specific for major β‐cell autoantigens, especially insulin. This opens the way towards new bioassays in the diagnosis of autoimmunity and towards autoantigen‐specific immunotherapy in T1D. In order to develop a new preclinical model of T1D that would allow testing insulin epitopes to induce immune tolerance in vivo, we developed a mouse that is deficient in endogenous major histocompatibility complex class I and class II genes and deficient for the two murine insulin genes and that express human class I, class II and insulin genes.
Candidate genes for type 1 diabetes modulate pancreatic islet inflammation and β‐cell apoptosis
Authors: Santin I. , Eizirik D. L.
Published: September 2013

Genome‐wide association studies (GWAS) have identified more than 50 loci associated with genetic risk of type 1 diabetes (T1D). Several T1D candidate genes have been suggested or identified within these regions, but the molecular mechanisms by which they contribute to insulitis and β‐cell destruction remain to be clarified. More than 60% of the T1D candidate genes are expressed in human pancreatic islets, suggesting that they contribute to T1D by regulating at least in part pathogenic mechanisms at the β‐cell level. Recent studies by our group indicate that important genetically regulated pathways in β‐cells include innate immunity and antiviral activity, involving RIG‐like receptors (particularly MDA5) and regulators of type I IFNs (i.e. PTPN2 and USP18), and genes related to β‐cell phenotype and susceptibility to pro‐apoptotic stimuli (i.e. GLIS3). These observations reinforce the concept that the early pathogenesis of T1D is characterized by a dialogue between the immune system and pancreatic β‐cells. This dialogue is probably influenced by polymorphisms in genes expressed at the β‐cell and/or immune system level, leading to inadequate responses to environmental cues such as viral infections. Further studies are needed to clarify how these disease‐associated variants affect pancreatic β‐cell responses to inflammation and the subsequent triggering of autoimmune responses and progressive β‐cell loss.