bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional analysis of ectodermal β‐catenin during external genitalia formation
Authors: Mazahery Ahmad Reza , Suzuki Kentaro , Nagafuchi Akira , Miyajima Masayasu , Nakagata Naomi , Orvis Grant D. , Behringer Richard R. , Yamada Gen
Published: October 2012

β‐catenin is a molecule belonging to the armadillo family of proteins that is a crucial core‐component of cellular adherens junctions, and a component of the canonical Wnt‐signaling pathway. We attempted to analyze the functional significance of ectodermal‐derived β‐catenin during the development of the mouse genital tubercle, a mammalian anlage of the external genitalia. For this purpose, the conditional loss of function mouse mutant Wnt7a‐Cre;β‐catf/f was utilized. Loss of ectodermal β‐catenin leads to the formation of urethral cleft during preputial uprising. Although expression of E‐cadherin was retained in the genital tubercle ectoderm of mutants, probably through plakoglobin compensatory expression, expression of other crucial adherens junction components such as α‐catenin and F‐actin in the cell‐cell border were distinctly reduced. We also showed that β‐catenin is necessary for the expression of its transcriptional downstream target Lef‐1 which was localized in the basal layer of the preputial ectoderm, excluding the midventral region at E15.5. Such specialized region was observed to possess cytoplasmic β‐catenin expression at this stage. Coincidentally, mitotically active cells were also found in the basal layer of the preputial ectoderm excluding the midventral region. In mutant genital tubercle, cell proliferation in the preputial ectoderm was decreased. Taken together, we suggest that ectodermal β‐catenin is necessary not only to maintain adherens junction integrity, but also to regulate cell proliferation possibly through Lef‐1 functions. Thus, β‐catenin is shown to perform dual functions, initially as an adhesion molecule and later on as a possible transcription factor.
Is multipleSNPtesting inBRCA2andBRCA1female carriers ready for use in clinical practice? Results from a large Genetic Centre in theUK
Authors: Ingham SL , Warwick J , Byers H , Lalloo F , Newman WG , Evans DGR
Published: October 2012

BRCA1andBRCA2are major breast cancer susceptibility genes. Nineteen single nucleotide polymorphisms (SNPs) at 18 loci have been associated with breast cancer. We aimed to determine whether these predict breast cancer incidence in women withBRCA1/BRCA2mutations.BRCA1/2mutation carriers identified through the Manchester genetics centre between 1996 and 2011 were included. Using published odds ratios (OR) and risk allele frequencies, we calculated an overall breast cancer riskSNPscore (OBRS) for each woman. The relationship betweenOBRSand age at breast cancer onset was investigated using the Cox proportional hazards model, and predictive ability assessed using Harrell'sCconcordance statistic. InBRCA1mutation carriers we found no association betweenOBRSand age at breast cancer onset:ORfor the lowest risk quintile compared to the highest was 1.20 (95%CI0.82–1.75, Harrell'sC = 0.54), but inBRCA2mutation carriers the association was significant (ORfor the lowest risk quintile relative to the highest was 0.47 (95%CI0.33–0.69, Harrell'sC = 0.59). The 18 validated breast cancerSNPsdifferentiate breast cancer risks between women withBRCA2mutations, but notBRCA1. It may now be appropriate to use theseSNPsto help women withBRCA2mutations make maximally informed decisions about management options.
Interferential therapy: a new treatment for slow transit constipation. A pilot study in adults
Authors: Queralto M. , Vitton V. , Bouvier M. , Abysique A. , Portier G.
Published: October 2012

Aim

The study aimed to assess, for the first time, the effectiveness of interferential therapy (IFT) in the treatment of slow transit constipation in adults and its impact on the quality of life.

Method

All consecutive patients with slow transit constipation diagnosed by symptomology and a colonic transit time (CTT) of > 100 h measured with radiopaque markers were included in this prospective study. IFT was performed for 1 h/day over 3 months. Clinical improvement was based on the stool diary and the Knowles–Eccersley–Scott Symptom and Cleveland Clinic Constipation Scores. Quality of life was assessed with the Gastrointestinal Quality of Life Index questionnaire.

Results

Eleven patients with a median age of 51 years were included. At the end of the follow‐up period, seven (63.6%) had significantly improved after IFT with a median of 0.66 stools per week [interquartile range (IQR) 0.33–0.66] before treatment and 1.66 (IQR 1.33–1.66) after (P = 0.007). The Knowles–Eccersley–Scott Symptom score changed from 30 (IQR 27–33) before treatment to 19 (IQR 17–26) after treatment (P = 0.005) and the Cleveland Clinic Constipation Score from 26 (IQR 25–28) to 17 (IQR 13–24; P = 0.005). The CTT improved from 103 h (IQR 101–113) to 98 h (IQR 94–107; P = 0.02). The Gastrointestinal Quality of Life Index score improved from 60 (IQR 57–63) to 95 (IQR 68–100; P = 0.005).

Conclusion

IFT is a new non‐invasive treatment for slow transit constipation. Further studies to confirm these results with longer follow‐up are necessary.
Predictors of hemoglobin response to eculizumab therapy in paroxysmal nocturnal hemoglobinuria
Authors: DeZern Amy E. , Dorr Donna , Brodsky Robert A.
Published: October 2012

Background

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, hematopoietic stem cell disorder that manifests with hemolytic anemia and bone marrow failure. Eculizumab has been shown to improve anemia, decrease intravascular hemolysis, and reduce the risk of thrombosis.

Design and methods

This is a retrospective, single‐center study of patients treated with eculizumab and categorized according to response criteria. Complete response (CR) was defined as transfusion independence with normal hemoglobin for age/sex, absence of symptoms, and lactate dehydrogenase <1.5 times the upper limit of normal. A good partial response (GPR) was defined as decreased transfusions from pretreatment and lactate dehydrogenase <1.5 upper limit of normal without thrombosis. These patients did not achieve normal hemoglobins for age and sex. A suboptimal response was defined as unchanged transfusion needs and persistent of symptoms.

Results

Thirty patients with PNH clones were treated with eculizumab and classified as complete responders (four patients), good partial responders (16), and suboptimal responders (10) over 863 patient‐months of treatment. Complete responders had a decrease in red cell clone size, while good partial responders had an increase. Thirteen patients treated did not meet inclusion criteria for the clinical trials of eculizumab due to lack of transfusions or thrombocytopenia; eight had at least a GPR.

Conclusions

Eculizumab is efficacious in patients with PNH, but responses can vary and may depend on underlying marrow failure, underlying inflammatory conditions and red cell clone size following treatment. Normalization of hemoglobin with decrease in red cell clone size may predict CR.
Plasticity in transmission strategies of the malaria parasite, Plasmodium chabaudi: environmental and genetic effects
Authors: Cameron Angus , Reece Sarah E. , Drew Damien R. , Haydon Daniel T. , Yates Andrew J.
Published: October 2012

Parasites may alter their behaviour to cope with changes in the within‐host environment. In particular, investment in transmission may alter in response to the availability of parasite resources or host immune responses. However, experimental and theoretical studies have drawn conflicting conclusions regarding parasites' optimal (adaptive) responses to deterioration in habitat quality. We analyse data from acute infections with six genotypes of the rodent malaria species Plasmodium chabaudi to quantify how investment in transmission (gametocytes) is influenced by the within‐host environment. Using a minimum of modelling assumptions, we find that proportional investment in gametocytogenesis increases sharply with host anaemia and also increases at low parasite densities. Further, stronger dependence of investment on parasite density is associated with greater virulence of the parasite genotype. Our study provides a robust quantitative framework for studying parasites' responses to the host environment and whether these responses are adaptive, which is crucial for predicting the short‐term and evolutionary impact of transmission‐blocking treatments for parasitic diseases.
Recovery of a nearly extinct Galápagos tortoise despite minimal genetic variation
Authors: Milinkovitch Michel C. , Kanitz Ricardo , Tiedemann Ralph , Tapia Washington , Llerena Fausto , Caccone Adalgisa , Gibbs James P. , Powell Jeffrey R.
Published: October 2012

A species of Galápagos tortoise endemic to Española Island was reduced to just 12 females and three males that have been bred in captivity since 1971 and have produced over 1700 offspring now repatriated to the island. Our molecular genetic analyses of juveniles repatriated to and surviving on the island indicate that none of the tortoises sampled in 1994 had hatched on the island versus 3% in 2004 and 24% in 2007, which demonstrates substantial and increasing reproduction in situ once again. This recovery occurred despite the parental population having an estimated effective population size <8 due to a combination of unequal reproductive success of the breeders and nonrandom mating in captivity. These results provide guidelines for adapting breeding regimes in the parental captive population and decreasing inbreeding in the repatriated population. Using simple morphological data scored on the sampled animals, we also show that a strongly heterogeneous distribution of tortoise sizes on Española Island observed today is due to a large variance in the number of animals included in yearly repatriation events performed in the last 40 years. Our study reveals that, at least in the short run, some endangered species can recover dramatically despite a lack of genetic variation and irregular repatriation efforts.
Introducing the patient's perspective in hospital health technology assessment (HTA): the views of HTA producers, hospital managers and patients
Authors: Gagnon Marie‐Pierre , Desmartis Marie , Gagnon Johanne , St‐Pierre Michèle , Gauvin François‐Pierre , Rhainds Marc , Lepage‐Savary Dolorès , Coulombe Martin , Dipankui Mylène Tantchou , Légaré France
Published: October 2012

Background

The recent establishment of health technology assessment (HTA) units in University hospitals in the Province of Quebec (Canada) provides a unique opportunity to foster increased participation of patients in decisions regarding health technologies and interventions at the local level. However, little is known about factors that influence whether the patient's perspective is taken into consideration when such decisions are made.

Objective

To explore the practices, perceptions and views of the various HTA stakeholders concerning patient involvement in HTA at the local level.

Method

Data were collected using semi‐structured interviews with 24 HTA producers and hospital managers and two focus groups with a total of 13 patient representatives.

Results

Patient representatives generally showed considerable interest in being involved in HTA. Our findings support the hypothesis that the patient perspective contributes to a more accurate and contextualized assessment of health technologies and produces HTA reports that are more useful for decision makers. They also suggest that participation throughout the assessment process could empower patients and improve their knowledge. Barriers to patient involvement in HTA at the local level are also discussed as well as potential strategies to overcome them.

Discussion and conclusion

This study contributes to knowledge that could guide interventions in favour of patient participation in HTA activities at the local level. Experimenting with different patient involvement strategies and assessing their impact is needed to provide evidence that will inform future interventions of this kind.
Piecing together the family portrait of TCR‐CD3 complexes
Authors: Kuhns Michael S. , Badgandi Hemant B.
Published: October 2012

The pre‐T‐cell receptor (TCR)‐, αβTCR‐, and γδTCR‐CD3 complexes are members of a family of modular biosensors that are responsible for driving T‐cell development, activation, and effector functions. They inform essential checkpoint decisions by relaying key information from their ligand‐binding modules (TCRs) to their signaling modules (CD3γε + CD3δε and CD3ζζ) and on to the intracellular signaling apparatus. Their actions shape the T‐cell repertoire, as well as T‐cell‐mediated immunity; yet, the mechanisms that underlie their activity remain an enigma. As with any molecular machine, understanding how they function depends upon understanding how their parts fit and work together. In the 30 years since the initial biochemical and genetic characterizations of the αβTCR, the structure and function of the individual components of these family members have been extensively characterized. Cumulatively, this information has allowed us to piece together a portrait of the αβTCR‐CD3 complex and outline the form of the remaining family members. Here we review the known structural and functional characteristics of the components of these TCR‐CD3 complex family members. We then discuss how these data have informed our understanding of the architecture of the αβTCR‐CD3 complex as well as their implications for the other family members. The intent is to provide a framework for considering: (i) how these thematically similar complexes diverge to execute their specific functions and (ii) how our knowledge of the form and function of these distinct family members can cross‐inform our understanding of the other family members.
Structural insights into key sites of vulnerability on HIV‐1 Env and influenza HA
Authors: Julien Jean‐Philippe , Lee Peter S. , Wilson Ian A.
Published: October 2012

Human immunodeficiency virus‐1 (HIV‐1) envelope protein (Env) and influenza hemagglutinin (HA) are the surface glycoproteins responsible for viral entry into host cells, the first step in the virus life cycle necessary to initiate infection. These glycoproteins exhibit a high degree of sequence variability and glycosylation, which are used as strategies to escape host immune responses. Nonetheless, antibodies with broadly neutralizing activity against these viruses have been isolated that have managed to overcome these barriers. Here, we review recent advances in the structural characterization of these antibodies with their viral antigens that defines a few sites of vulnerability on these viral spikes. These broadly neutralizing antibodies tend to focus their recognition on the sites of similar function between the two viruses: the receptor‐binding site and membrane fusion machinery. However, some sites of recognition are unique to the virus neutralized, such as the dense shield of oligomannose carbohydrates on HIV‐1 Env. These observations are discussed in the context of structure‐based design strategies to aid in vaccine design or development of antivirals.
Non‐catalytic tyrosine‐phosphorylated receptors
Authors: Dushek Omer , Goyette Jesse , van der Merwe P. Anton
Published: October 2012

Leukocytes play a critical role in recognizing and responding to infection and cancer. Central to this function is an array of cell‐surface receptors that lack sequence homology. Many of these receptors have in common the fact that their signaling involves phosphorylation of cytoplasmic domains by extrinsic tyrosine kinases. These non‐catalytic tyrosine‐phosphorylated receptors (NTRs) share a number of other features, including small size and optimal stimulation by surface–associated ligands. We argue here that NTRs are also likely to share the same kinetic‐segregation triggering mechanism, which involves segregation of the engaged NTR from receptor tyrosine phosphatases with large ectodomains such as CD45 and CD148. NTRs signal through tyrosine‐containing cytoplasmic motifs, which recruit distinct cytoplasmic signaling proteins when phosphorylated, transducing activatory or inhibitory signals. They have two features that make them uniquely well suited to their role in immune recognition of infection and cancer. Their modular structure enables the coupling of many rapidly evolving receptors with diverse ligand specificities to the same conserved signaling machinery. Their similarity in size and shared signaling machinery enables them to colocalize at cell‐cell interfaces when they engage ligands, facilitating the integration of activatory and inhibitory signals from multiple receptors at the cell surface.
Subversion of cytokine networks by virally encoded decoy receptors
Authors: Epperson Megan L. , Lee Chung A. , Fremont Daved H.
Published: October 2012

During the course of evolution, viruses have captured or created a diverse array of open reading frames, which encode for proteins that serve to evade and sabotage the host innate and adaptive immune responses that would otherwise lead to their elimination. These viral genomes are some of the best textbooks of immunology ever written. The established arsenal of immunomodulatory proteins encoded by viruses is large and growing, and includes specificities for virtually all known inflammatory pathways and targets. The focus of this review is on herpes and poxvirus‐encoded cytokine and chemokine‐binding proteins that serve to undermine the coordination of host immune surveillance. Structural and mechanistic studies of these decoy receptors have provided a wealth of information, not only about viral pathogenesis but also about the inner workings of cytokine signaling networks.
Isolation of novel microsatellite loci in the black goby Gobius niger and cross‐amplification in other gobiid species (Perciformes, Gobiidae)
Authors: Ruggeri P. , Splendiani A. , Giovannotti M. , Nisi Cerioni P. , Caputo V.
Published: October 2012

Twelve microsatellite loci were isolated from and characterized for the black goby Gobius niger. These loci were tested on a total of 48 individuals from two geographically distant locations (Orbetello and Cattolica) and the number of alleles ranged from two to 18, with expected (He) and observed (Ho) heterozygosities ranging from 0·042 to 0·941 and from 0·042 to 0·917, respectively. The loci described were used to cross‐amplify other gobiid species belonging to Gobius, Zosterisessor, Lesueurigobius and Aphia.
Farther, slower, stronger: how the plant genetic background protects a major resistance gene from breakdown
Authors: Quenouille Julie , Montarry Josselin , Palloix Alain , Moury Benoit
Published: October 2012

Genetic resistance provides efficient control of crop diseases, but is limited by pathogen evolution capacities which often result in resistance breakdown. It has been demonstrated recently, in three different pathosystems, that polygenic resistances combining a major‐effect gene and quantitative resistance controlled by the genetic background are more durable than monogenic resistances (with the same major gene in a susceptible genetic background), but the underlying mechanisms are unknown. Using the pepper–Potato virus Y system, we examined three mechanisms that could account for the greater durability of the polygenic resistances: (i) the additional quantitative resistance conferred by the genetic background; (ii) the increase in the number of mutations required for resistance breakdown; and (iii) the slower selection of adapted resistance‐breaking mutants within the viral population. The three mechanisms were experimentally validated. The first explained a large part of the variation in resistance breakdown frequency and is therefore expected to be a major determinant of resistance durability. Quantitative resistance factors also had an influence on the second mechanism by modifying the virus mutational pathways towards resistance breakdown and could also have an influence on the third mechanism by increasing genetic drift effects on the viral population. The relevance of these results for other plant–pathogen systems and their importance in plant breeding are discussed.
Towards an understanding of West African montane forest response to climate change
Authors: Lézine Anne‐Marie , Assi‐Kaudjhis Chimène , Roche Emile , Vincens Annie , Achoundong Gaston
Published: October 2012

Aim

Our aims were to provide a detailed chronology of past vegetation changes in the tropical mountains of west‐central Africa since the Last Glacial Maximum and to discuss montane forest responses to climate change in terms of distribution and biodiversity.

Location

Lake Bambili, western Cameroon (05°56′ N, 10°14′ E, 2273 m a.s.l.).

Methods

Fossil pollen was extracted from a long, continuous and well‐dated sedimentary sequence extending back 20,000 years. Pollen diversity and evenness estimates were based on rarefaction analysis and on Simpson's (1/D) index.

Results

Forest was nearly absent from high elevations during the last glacial period. It expanded gradually from 18.4 cal. kyr bp, interrupted only by reversals coincident with the Heinrich 1 (H1) and Younger Dryas (YD) climatic events, and then suddenly collapsed at 3.3 cal. kyr bp. This switch from forest to grassland communities occurred within a time span of three centuries. After 3.3 cal. kyr bp only short and taxon‐poor forest phases are recorded, specifically between 2.7 and 1 cal. kyr bp and in recent centuries.

Main conclusions

Our data indicate that the mountain forests of Cameroon are recent, resulting from plant migrations from various sources from 18.4 cal. kyr bp onwards. Their progressive development closely followed intensification of the Atlantic monsoon, leading to the formation of a dense forest between 11.7 and 3.3 cal. kyr bp. The composition of this forest included the co‐occurrence of species whose ranges do not overlap today, and indicates the potential for the development of unique iterations of climax forests through time. These forests appear to be very sensitive to Northern Hemisphere climate change, with phases of expansion/contraction coeval with the boreal deglacial signal, including widely recognized events such as H1, the YD and the 8.2 ka event. From 8.2 cal. kyr bp onwards, the progressive opening of the canopy is likely to reflect increased seasonality in rainfall related to more frequent El Niño/Southern Oscillation (ENSO) events. The final step of this history was the collapse of the montane forest at 3.3 cal. kyr bp. During the last millennium, very severe disruptions have meant that only the most rapidly dispersing species could spread, contributing to a drastic loss of forest biodiversity that has been accentuated by human impact in the last few centuries.
Recent demographic history of cactophilic Drosophila species can be related to Quaternary palaeoclimatic changes in South America
Authors: Franco Fernando Faria , Manfrin Maura Helena
Published: October 2012

Aim

The aim of this paper is to investigate the influence and extent of past climatic changes on South American biota. To this end, we establish phylogeographical hypotheses for a monophyletic group of four cactophilic species of Drosophila (the Drosophila serido haplogroup) found in xeromorphic vegetation in Brazil. The effects of Quaternary palaeoclimatic oscillations on the demographic fluctuations of our biological model and its sister group Drosophila antonietae are investigated.

Location

Areas of eastern Brazil with open vegetation, including seasonally dry tropical forest (SDTF) areas and montane savannas, which are disjunctly distributed in eastern Brazil. We also analysed populations of sand dune vegetation from littoral areas in Brazil.

Methods

Nucleotide information from 630 bp of the cytochrome c oxidase subunit I gene from 441 individuals was used to perform a series of statistical analyses to infer a phylogeographical hypothesis for each species and to date the divergence time between the D. serido and D. antonietae haplogroups.

Results

All of the analysed species experienced population expansion during the Pleistocene, probably following the historical migratory routes that have been proposed for the expansion of SDTFs in Brazil. A bottleneck event in the Holocene was inferred for Drosophila seriema, probably due to ecological factors related to the geographical distribution of the host plant. The divergence time for the D. serido and D. antonietae haplogroups was calculated to have occurred during the early Pleistocene.

Main conclusions

Geographical and chronological evidence suggests that the major vicariant events between the D. serido and D. antonietae haplogroups, as well as the demographic fluctuations in each of the species within these lineages, could be related to the causal effects of Quaternary palaeoclimatic changes on the spatial dynamics of the SDTFs in Brazil.
Effects of controlled discontinuation of long‐term used antipsychotics for behavioural symptoms in individuals with intellectual disability
Authors: de Kuijper G. , Evenhuis H. , Minderaa R. B. , Hoekstra P. J.
Published: October 2012

Background

Antipsychotics are frequently and often long‐term used for challenging behaviour in persons with intellectual disability (ID), but the evidence base for this is meagre. As these agents may cause harmful side effects, discontinuation should be considered. Previous studies regarding discontinuation of long‐term used antipsychotics mostly were uncontrolled and involved small numbers.

The primary objective was to investigate the effects of controlled discontinuation of antipsychotics prescribed for challenging behaviour. Secondary objectives were to compare the results of two discontinuation time schedules, to compare groups of participants who had and had not achieved complete discontinuation, and to identify patient and medication characteristics that might predict the outcomes. Our hypothesis was that discontinuation of antipsychotics used for behavioural symptoms would not lead to worsening in behaviour.

Methods

This was a multi‐centre parallel‐group study comparing two discontinuation schedules of 14 and 28 weeks. Allocation to the two discontinuation schedules took place in a 1:1 ratio. Antipsychotics were tapered off every 2 or 4 weeks with approximately 12.5% of the initial dosage. Follow‐up was 12 weeks after the scheduled complete discontinuation, that is, 26 or 40 weeks after the first dose reduction, respectively. Discontinuation was stopped in case of significant behavioural worsening.

Participants were 98 residents with ID of three care providing organisations in the Netherlands, aged 15–66 year, who had used for more than 1 year one or more of the six most frequently prescribed antipsychotics for challenging behaviour. Main outcome measure was the total score of the Aberrant Behaviour Checklist (ABC); also ABC sub‐scales were used.

Results

Of 98 participants, 43 achieved complete discontinuation; at follow‐up 7 had resumed use of antipsychotics. Mean ABC ratings improved significantly for those who achieved complete discontinuation (directly after discontinuation, P < 0.01 and at follow‐up, P = 0.03), and at follow‐up (P = 0.03) for those who had not achieved complete discontinuation. Similar results were found with respect to most ABC sub‐scales, including the ‘irritability’ sub‐scale. There were no significant differences in improvement of ABC ratings between both discontinuation schedules. Higher ratings of extrapyramidal and autonomic symptoms at baseline were associated with less improvement of behavioural symptoms after discontinuation; higher baseline ABC rating predicted higher odds of incomplete discontinuation.

Conclusions

Discontinuation of antipsychotics prescribed for challenging behaviour in patients with ID is associated with improved behavioural functioning. There is no need to taper off in a time frame longer than 14 weeks.
Insecticide resistance monitoring of field‐collected Anopheles gambiae s.l. populations from Jinja, eastern Uganda, identifies high levels of pyrethroid resistance
Authors: MAWEJJE H. D. , WILDING C. S. , RIPPON E. J. , HUGHES A. , WEETMAN D. , DONNELLY M. J.
Published: October 2012

Insecticide resistance in the malaria vector Anopheles gambiae s.l. (Diptera: Culicidae) threatens insecticide‐based control efforts, necessitating regular monitoring. We assessed resistance in field‐collected An. gambiae s.l. from Jinja, Uganda using World Health Organization (WHO) biosassays. Only An. gambiae s.s. and An. arabiensis (≅70%) were present. Female An. gambiae exhibited extremely high pyrethroid resistance (permethrin LT50 > 2 h; deltamethrin LT50 > 5 h). Female An. arabiensis were resistant to permethrin and exhibited reduced susceptibility to deltamethrin. However, while An. gambiae were DDT resistant, An. arabiensis were fully susceptible. Both species were fully susceptible to bendiocarb and fenitrothion. Kdr 1014S has increased rapidly in the Jinja population of An. gambiae s.s. and now approaches fixation (≅95%), consistent with insecticide‐mediated selection, but is currently at a low frequency in An. arabiensis (0.07%). Kdr 1014F was also at a low frequency in An. gambiae. These frequencies preclude adequately‐powered tests for an association with phenotypic resistance. PBO synergist bioassays resulted in near complete recovery of pyrethroid susceptibility suggesting involvement of CYP450s in resistance. A small number (0.22%) of An. gambiae s.s. ×An. arabiensis hybrids were found, suggesting the possibility of introgression of resistance alleles between species. The high levels of pyrethroid resistance encountered in Jinja threaten to reduce the efficacy of vector control programmes which rely on pyrethroid‐impregnated bednets or indoor spraying of pyrethroids.
Review: Axon pathology in age‐related neurodegenerative disorders
Authors: Adalbert R. , Coleman M. P.
Published: October 2012

‘Dying back’ axon degeneration is a prominent feature of many age‐related neurodegenerative disorders and is widespread in normal ageing. Although the mechanisms of disease‐ and age‐related losses may differ, both contribute to symptoms. Here, we review recent advances in understanding axon pathology in age‐related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. In particular, we highlight the importance of axonal transport, autophagy, traumatic brain injury and mitochondrial quality control. We then place these disease mechanisms in the context of changes to axons and dendrites that occur during normal ageing. We discuss what makes ageing such an important risk factor for many neurodegenerative disorders and conclude that the processes of normal ageing and disease combine at the molecular, cellular or systems levels in a range of disorders to produce symptoms. Pathology identical to disease also occurs at the cellular level in most elderly individuals. Thus, normal ageing and age‐related disease are inextricably linked and the term ‘healthy ageing’ downplays the important contributions of cellular pathology. For a full understanding of normal ageing or age‐related disease we must study both processes.
Spatiotemporal distribution of flavescence dorée phytoplasma in grapevine
Authors: Prezelj N. , Nikolić P. , Gruden K. , Ravnikar M. , Dermastia M.
Published: October 2012

In this study quantitative real‐time PCR was used to follow the seasonal changes of flavescence dorée phytoplasma (FDp) titre in grapevines of cv. Modra frankinja (syn. Blaufränkisch) and cv. Refošk (syn. Refosco'd'Istria) from two vineyards located in climatically different vine‐growing regions of Slovenia. Besides its known presence in the leaf veins, FDp was also detected in flowers, berry tissues and tendrils. In plants with high concentrations of FDp in tissues with symptoms, phytoplasma was also detected in symptomless tissues. A trend of decreasing FDp titre in all examined symptomless tissues from June to July and an increasing one throughout the growing season in tissues with symptoms was recorded. Accordingly, FDp was present in detectable amounts in flowers, petioles and veins of almost all infected plants in the late spring, and was detected in all examined tissue types in summer, with the highest titre in berries in August. The study showed that in the absence of plant health measurements an FDp infection may spread exponentially by a factor of 40 per year.
Labor law violations in Japanese public hospitals from March 2002 to March 2011
Authors: Ehara Akira
Published: October 2012

Background

According to the Japan Pediatric Society, the mean extra work hours of hospital pediatricians in 2010 was approximately 80 h per month, which is the certification criterion for Karoshi (death from overwork), but there is no precise picture of personnel management at hospitals because the labor authorities do not disclose detailed statistics concerning labor law violations to the public.

Methods

Most local governments have a disclosure system, and the local governments that operate public hospitals were requested to disclose warning documents issued by the labor authorities from March 2002 to March 2011.

Results

A total of 208/369 public hospitals (56.4%) with ≥200 beds in Japan were warned of labor law violations. Offenses included exceeding the limit of working hours (177 hospitals) and non‐payment of increased wages for night and holiday work (98 hospitals).

Conclusions

Many public hospitals in Japan did not always pay workers including physicians for increased workload because they do not regard night and holiday duties as work hours.
Spontaneous tension pneumothorax: what is it and does it exist?
Authors: Simpson G. , Vincent S. , Ferns J.
Published: October 2012

Tension pneumothorax is variously defined but is generally thought of as a pneumothorax in which the pressure of intrapleural gas exceeds atmospheric pressure, producing adverse effects, including mediastinal shift associated with cardiovascular collapse, often attributed to reduced venous return and kinking of the great vessels. The mechanism of tension pneumothorax is said to be a valvular defect in the visceral pleura such that air enters the pleural space in inspiration but cannot exit in expiration, leading to a progressive increase in pressure. However, as the driving pressure forcing air into the pleura in inspiration is atmospheric pressure, the pleural pressure can never exceed 1 atm during inspiration in a spontaneously breathing subject. Furthermore, all pneumothoraces must have pressures greater than atmospheric during expiration, or conventional treatment with intercostal tube drainage would not work. Pilot experiments have failed to show any re‐entry of pleural gas into the lung in patients with persistent air leaks but no evidence of tension, suggesting these behave as valvular pneumothoraces. Case reports of tension pneumothorax in spontaneously breathing patients are rare, and most patients have other explanations for clinical deterioration. Although a large and rapidly expanding pneumothorax may require urgent intervention, it is unlikely that the effects are mediated by high intrapleural pressures. The term tension pneumothorax in spontaneously breathing patients should be reconsidered.
Deficits in volitional oculomotor control align with language status in autism spectrum disorders
Authors: Kelly David J. , Walker Robin , Norbury Courtenay Frazier
Published: October 2012

Eye‐tracking paradigms are increasingly used to investigate higher‐level social and cognitive processing in autism spectrum disorder (ASD). However, the integrity of the oculomotor system within ASD is unclear, with contradictory reports of aberrant eye‐movements on basic oculomotor tasks. The purpose of the current study was to determine whether reducing population heterogeneity and distinguishing neurocognitive phenotypes can clarify discrepancies in oculomotor behaviour evident in previous reports. Reflexive and volitional eye‐movement control was assessed in 73 children aged 8–14 years from four distinct groups: Autism Language Normal (ALN), Autism Language Impaired (ALI), non‐autistic Language Impaired (LI) and Typically Developing (TD). Eye‐movement control was measured using pro‐ and antisaccade tasks and a novel ‘search distracter’ task to measure distractibility. Reflexive eye‐movements were equivalent across groups, but deficits in volitional eye‐movement control were found that aligned with language status, and were not specific to ASD. More than 80% of ALI and LI children presented error rates at least 1.5 SDs below the TD mean in an antisaccade task. In the search distracter task, 35.29% of ALI children and 43.75% of LI children had error rates greater than 1.5 SDs compared with 17.64% of ALN children. A significant proportion of children with neurodevelopmental disorders involving language function have pronounced difficulties suppressing reflexive saccades and maintaining fixations in the presence of competing stimuli. We extend the putative link between ALI and LI populations to non‐language tasks, and highlight the need to account for co‐morbidity in understanding the ontogenesis of ASD.
Vested Interest theory and disaster preparedness
Authors: Miller Claude H. , Adame Bradley J. , Moore Scott D.
Published: October 2012

Three studies were designed to extend a combination of vested interest theory (VI) and the extended parallel process model of fear appeals (EPPM) to provide formative research for creating more effective disaster preparedness social action campaigns. The aim was to develop an effective VI scale for assessing individual awareness and ‘vestedness’ relevant to disaster preparedness. Typical preparedness behaviours are discussed with emphasis on earthquakes and tornados in particular. Brief overviews of VI and the EPPM are offered, and findings are presented from three studies (one dealing with earthquakes, and two with tornados) conducted to determine the factor structure of the key VI components involved, and to develop and test subscales derived from the two theories. The paper finishes with a discussion of future research needs and suggestions on how the new subscales may be applied in the design and execution of more effective disaster preparedness campaigns.
Social Capital and Ethno-racial Diversity: Learning to Trust in an Immigrant Society
Authors: Stolle Dietlind , Harell Allison
Published: October 2012

This article builds on the insights of the contact hypothesis and political socialization literatures to go beyond recent findings that racial and ethnic diversity have overwhelmingly negative effects on social capital, particularly generalized trust. Using the Canadian General Social Survey (2003), our results show that despite a negative relationship among adults, younger Canadians with racial and ethnic diversity in their social networks show higher levels of generalized trust. The results seem to confirm that youth socialization experiences with rising diversity and the normalization of diversity in a multicultural environment contribute to beneficial (instead of detrimental) effects of diverse social networks.
Center-Right Parties in Peace Processes: ‘Slow Learning’ or Punctuated Peace Socialization?
Authors: Sandal Nukhet , Loizides Neophytos
Published: October 2012

This article examines why center-right parties that have partly built their image around ethnic or religious identities reverse their positions to support peace arrangements. Political settlements in divided societies frequently run counter to the values of these parties and are also potentially damaging to their internal party cohesion. We argue that political learning through sustained interaction with external pro-peace allies transforms the positions of center-right parties by socializing them when it comes to their international agenda, yet the same effect is not observed in party actions within the sphere of domestic intra-communal politics. Drawing from the Cypriot and Northern Irish peace processes, we show that once these parties embrace peace agreements, they do so by balancing international and local considerations, choosing to compensate domestic constituencies on symbolic issues of less importance for the peace process yet of major significance to conservative constituencies. The study of center-right and conservative peace actors has important implications for research on mediation and international conflict since it suggests mechanisms through which policy makers can better engage with ethnic or religious parties in fragile peace processes.
Lone Parents and Welfare‐to‐Work in England: A Spatial Analysis of Outcomes and Drivers
Authors: Whitworth Adam
Published: October 2012

Mirroring changes across nations of the Organisation for Economic Co‐operation and Development, recent UK governments have redrawn lone parents' entitlement to social assistance benefits ever tighter around participation in the labour market. A radical shift since 2008 has been the gradual transfer of most non‐employed lone parents into the ‘activating’ Jobseekers' Allowance (JSA) regime. The enhanced conditionality requirements of this JSA regime have been justified by both paternalistic and contractualist arguments but, however justified, are built on the premise that behavioural factors drive lone parent employment outcomes, a view made increasingly forcefully under the current Coalition government. This article uses up‐to‐date administrative data at local authority level across England to provide a geographical perspective into the sub‐national changes in lone parent employment outcomes since the transfer to JSA from 2008, as well as the relevant importance of the alternative structural and behavioural accounts to these outcomes. The findings suggest that the JSA transfer has increased lone parent employment, that structural rather than behavioural drivers are more relevant causal factors and that there is good reason to be concerned about the effect of the reforms on the well‐being of lone parents and their children.
Attributing Outcomes to Social Policy Interventions – ‘Gold Standard’ or ‘Fool's Gold’ in Public Policy and Management?
Authors: Bovaird Tony
Published: October 2012

In recent years there has been increased interest in outcome‐based social policy‐making and management. TheUKhas been in the forefront of this movement but similar movements have been identified internationally. This interest in outcome‐based decision‐making has been given particular impetus through the ‘results’‐based movement in evaluation and performance management since the 1980s, which has increased in scope over time, slowly changing its emphasis from cost reduction and measuring outputs to measuring outcomes. This change has been widely welcomed by policymakers, practitioners and academics. However, there is evidence that the reality is often rather less than the rhetoric. Moreover, the ‘attribution problem’ of attributing changes in outcomes to specific social policies has remained a major issue. The conceptual solution of constructing ‘cause‐and‐effect’ models, imported from the policy evaluation field, has only recently become common for operationalising these models. This article outlines the evolution of interest in outcome‐based social policy‐making up to recent times and the growing realization of the importance of the attribution problem. It then outlines both how the ‘cause‐and‐effect’ policy modelling approach can partially tackle the attribution problem, but also its inherent limitations. Lastly, the article uses several case studies in currentUKsocial policy‐making to demonstrate the potential importance of the reasoning embedded within cause‐and‐effect models but also the dangers in policy‐making which adopts this approach without understanding its conceptual basis or in fields where it is inappropriate, given the current state of our knowledge of social policy systems.
Slope Analysis of Fuzzy Surfaces
Authors: Caha Jan , Tuček Pavel , Vondráková Alena , Paclíková Lenka
Published: October 2012

Analysis of the slope is one of the fundamental analyses within geoinformatics, especially its initial calculation. Slope analysis is usually used as the first step in much more sophisticated analyses as well as in complex models of natural phenomena. Fuzzy surfaces provide representation of geographical phenomena with all aspects of the uncertainty (i.e. both in terms of the description of reality or the uncertainty of measurement). The uncertainty in the input surface is crucial for analysis of slope. A high level of uncertainty can significantly affect the result of slope analysis. The Neighbourhood method was utilized for calculating with fuzzy numbers and to perform slope analysis of the fuzzy surface. The main reason for choosing this method is that it belongs to the most common tools in GIS software (e.g. both ArcGIS and GRASS). The computation with fuzzy numbers instead of crisp numbers allows evaluation of uncertainty of the resultant slope. The aim of this article is to present the process of slope calculation with fuzzy numbers as well as all necessary algorithms that are needed for such calculation. The further analysis of uncertainty provides important information for the process of decision making. The level of uncertainty in the results of the above‐mentioned analysis can be as important as the actual result. It is especially important in situations where the amount of uncertainty varies at higher values.
Geo‐Social Model: A Conceptual Framework for Real‐time Geocollaboration
Authors: Chang Zheng (Eric) , Li Songnian
Published: October 2012

Synchronous geocollaboration helps geographically dispersed people to work together in a shared geospatial environment. Its real‐time nature, multiple users' interaction and diversity of work context impose some special social, organizational and technological requirements, making the development of such real‐time geocollaboration systems a challenging task. A conceptual framework is therefore needed to specify and describe what synchronous geocollaboration is, considering its social, spatial and technical aspects. The geo‐social model presented in this article describes a conceptual framework for synchronous geocollaboration systems addressing the above aspects, identifies the core elements of the system and describes how these elements collaborate with each other. This model is presented using application‐level ontology and is then applied to a multi‐agent system based prototype in which multiple users can interact and negotiate in a shared 3D geospatial environment.
PERILOUS WATERS: EARLY MARITIME TRADE ALONG THE WESTERN COAST OF THE BLACK SEA (FIFTH MILLENNIUM BC)
Authors: IVANOVA MARIYA
Published: October 2012

A heavy accumulation of exotica and valuables, such as gold, copper, carnelian and Mediterranean shells, distinguishes the Black Sea littoral from other parts of the east Balkans in the fifth millennium BC.1 Recent discoveries shed new light on the trading connections of the coastal communities and indicate that maritime activity was germane to the origin of their extraordinary wealth. This article investigates the involvement of the coastal inhabitants with the sea. It addresses the ecological conditions and the technical parameters of prehistoric seafaring on the west coast of the Black Sea, considers the remains of marine species in the faunal record as an indication of maritime experience, and examines the artefactual record for signs of movement of goods and people between the coastal communities. The combination of these separate lines of evidence points to a maritime trading route joining the resource‐poor north with the resource‐rich south of the littoral in the Chalcolithic period. Moreover, it implies that sea‐borne trade not only enabled the accumulation of material wealth, but also was pivotal for social change.