bluuebunny/crossref_metadata_2025 huggingface dataset:
Training an asymmetric signal perceptron through reinforcement in an artificial chemistry
Authors: Banda Peter , Teuscher Christof , Stefanovic Darko
Published: January 2014

State-of-the-art biochemical systems for medical applications and chemical computing are application-specific and cannot be reprogrammed or trained once fabricated. The implementation of adaptive biochemical systems that would offer flexibility through programmability and autonomous adaptation faces major challenges because of the large number of required chemical species as well as the timing-sensitive feedback loops required for learning. In this paper, we begin addressing these challenges with a novel chemical perceptron that can solve all 14 linearly separable logic functions. The system performs asymmetric chemical arithmetic, learns through reinforcement and supports both Michaelis–Menten as well as mass-action kinetics. To enable cascading of the chemical perceptrons, we introduce thresholds that amplify the outputs. The simplicity of our model makes an actual wet implementation, in particular by DNA-strand displacement, possible.
Optimal feedback correction in string quartet synchronization
Authors: Wing Alan M. , Endo Satoshi , Bradbury Adrian , Vorberg Dirk
Published: January 2014

Control of relative timing is critical in ensemble music performance. We hypothesize that players respond to and correct asynchronies in tone onsets that arise from fluctuations in their individual tempos. We propose a first-order linear phase correction model and demonstrate that optimal performance that minimizes asynchrony variance predicts a specific value for the correction gain. In two separate case studies, two internationally recognized string quartets repeatedly performed a short excerpt from the fourth movement of Haydn's quartet Op. 74 no. 1, with intentional, but unrehearsed, expressive variations in timing. Time series analysis of successive tone onset asynchronies was used to estimate correction gains for all pairs of players. On average, both quartets exhibited near-optimal gain. However, individual gains revealed contrasting patterns of adjustment between some pairs of players. In one quartet, the first violinist exhibited less adjustment to the others compared with their adjustment to her. In the second quartet, the levels of correction by the first violinist matched those exhibited by the others. These correction patterns may be seen as reflecting contrasting strategies of first-violin-led autocracy versus democracy. The time series approach we propose affords a sensitive method for investigating subtle contrasts in music ensemble synchronization.
Females allocate differentially to offspring size and number in response to male effects on female and offspring fitness
Authors: Kindsvater Holly K. , Alonzo Suzanne H.
Published: January 2014

Female investment in offspring size and number has been observed to vary with the phenotype of their mate across diverse taxa. Recent theory motivated by these intriguing empirical patterns predicted both positive (differential allocation) and negative (reproductive compensation) effects of mating with a preferred male on female investment. These predictions, however, focused on total reproductive effort and did not distinguish between a response in offspring size and clutch size. Here, we model how specific paternal effects on fitness affect maternal allocation to offspring size and number. The specific mechanism by which males affect the fitness of females or their offspring determines whether and how females allocated differentially. Offspring size is predicted to increase when males benefit offspring survival, but decrease when males increase offspring growth rate. Clutch size is predicted to increase when males contribute to female resources (e.g. with a nuptial gift) and when males increase offspring growth rate. The predicted direction and magnitude of female responses vary with female age, but only when per-offspring paternal benefits decline with clutch size. We conclude that considering specific paternal effects on fitness in the context of maternal life-history trade-offs can help explain mixed empirical patterns of differential allocation and reproductive compensation.
Interactions between fungi and bacteria influence microbial community structure in the
Megachile rotundata
larval gut
Authors: McFrederick Quinn S. , Mueller Ulrich G. , James Rosalind R.
Published: January 2014

Recent declines in bee populations coupled with advances in DNA-sequencing technology have sparked a renaissance in studies of bee-associated microbes.
Megachile rotundata
is an important field crop pollinator, but is stricken by chalkbrood, a disease caused by the fungus
Ascosphaera aggregata
. To test the hypothesis that some gut microbes directly or indirectly affect the growth of others, we applied four treatments to the pollen provisions of
M. rotundata
eggs and young larvae: antibacterials, antifungals,
A. aggregata
spores and a no-treatment control. We allowed the larvae to develop, and then used 454 pyrosequencing and quantitative PCR (for
A. aggregata
) to investigate fungal and bacterial communities in the larval gut. Antifungals lowered
A. aggregata
abundance but increased the diversity of surviving fungi. This suggests that
A. aggregata
inhibits the growth of other fungi in the gut through chemical or competitive interaction. Bacterial richness decreased under the antifungal treatment, suggesting that changes in the fungal community caused changes in the bacterial community. We found no evidence that bacteria affect fungal communities.
Lactobacillus kunkeei
clade bacteria were common members of the larval gut microbiota and exhibited antibiotic resistance. Further research is needed to determine the effect of gut microbes on
M. rotundata
health.
Temperature-responsive release of thyroxine and its environmental adaptation in Australians
Authors: Qi Xiaoqiang , Chan Wee Lee , Read Randy J. , Zhou Aiwu , Carrell Robin W.
Published: January 2014

The hormone thyroxine that regulates mammalian metabolism is carried and stored in the blood by thyroxine-binding globulin (TBG). We demonstrate here that the release of thyroxine from TBG occurs by a temperature-sensitive mechanism and show how this will provide a homoeostatic adjustment of the concentration of thyroxine to match metabolic needs, as with the hypothermia and torpor of small animals. In humans, a rise in temperature, as in infections, will trigger an accelerated release of thyroxine, resulting in a predictable 23% increase in the concentration of free thyroxine at 39°C. The
in vivo
relevance of this fever-response is affirmed in an environmental adaptation in aboriginal Australians. We show how two mutations incorporated in their TBG interact in a way that will halve the surge in thyroxine release, and hence the boost in metabolic rate that would otherwise occur as body temperatures exceed 37°C. The overall findings open insights into physiological changes that accompany variations in body temperature, as notably in fevers.
Costs of deception and learned resistance in deceptive interactions
Authors: de Jager Marinus L. , Ellis Allan G.
Published: January 2014

The costs that species suffer when deceived are expected to drive learned resistance, although this relationship has seldom been studied experimentally. Flowers that elicit mating behaviour from male insects by mimicking conspecific females provide an ideal system for such investigation. Here, we explore interactions between a sexually deceptive daisy with multiple floral forms that vary in deceptiveness, and the male flies that pollinate it. We show that male pollinators are negatively impacted by the interaction, suffering potential mating costs in terms of their ability and time taken to locate genuine females within deceptive inflorescences. The severity of these costs is determined by the amount of mating behaviour elicited by deceptive inflorescences. However, inexperienced male flies exhibit the ability to learn to discriminate the most deceptive inflorescences as female mimics and subsequently reduce the amount of mating behaviour they exhibit on them with increased exposure. Experienced males, which interact with sexually deceptive forms naturally, exhibit similar patterns of reduced mating behaviour on deceptive inflorescences in multiple populations, indicating that pollinator learning is widespread. As sexually deceptive plants are typically dependent on the elicitation of mating behaviour from male pollinators for pollination, this may result in antagonistic coevolution within these systems.
Rapid increase in southern elephant seal genetic diversity after a founder event
Authors: de Bruyn Mark , Pinsky Malin L. , Hall Brenda , Koch Paul , Baroni Carlo , Hoelzel A. Rus
Published: January 2014

Genetic diversity provides the raw material for populations to respond to changing environmental conditions. The evolution of diversity within populations is based on the accumulation of mutations and their retention or loss through selection and genetic drift, while migration can also introduce new variation. However, the extent to which population growth and sustained large population size can lead to rapid and significant increases in diversity has not been widely investigated. Here, we assess this empirically by applying approximate Bayesian computation to a novel ancient DNA dataset that spans the life of a southern elephant seal (Mirounga leonina) population, from initial founding approximately 7000 years ago to eventual extinction within the past millennium. We find that rapid population growth and sustained large population size can explain substantial increases in population genetic diversity over a period of several hundred generations, subsequently lost when the population went to extinction. Results suggest that the impact of diversity introduced through migration was relatively minor. We thus demonstrate, by examining genetic diversity across the life of a population, that environmental change could generate the raw material for adaptive evolution over a very short evolutionary time scale through rapid establishment of a large, stable population.
Role of Lactobacillus reuteri cell and mucus-binding protein A (CmbA) in adhesion to intestinal epithelial cells and mucus in vitro
Authors: Jensen Hanne , Roos Stefan , Jonsson Hans , Rud Ida , Grimmer Stine , van Pijkeren Jan-Peter , Britton Robert A. , Axelsson Lars
Published: January 2014

Lactobacillus reuteri, a symbiotic inhabitant of the gastrointestinal tract in humans and animals, is marketed as a probiotic. The ability to adhere to intestinal epithelial cells and mucus is an interesting property with regard to probiotic features such as colonization of the gastrointestinal tract and interaction with the host. Here, we present a study performed to elucidate the role of sortase (SrtA), four putative sortase-dependent proteins (SDPs), and one C-terminal membrane-anchored cell surface protein ofLactobacillus reuteriATCC PTA 6475 in adhesion to Caco-2 cells and mucusin vitro. This included mutagenesis of the genes encoding these proteins and complementation of mutants. A null mutation inhmpref0536_10255encodingsrtAresulted in significantly reduced adhesion to Caco-2 cells and mucus, indicating involvement of SDPs in adhesion. Evaluation of the bacterial adhesion revealed that of the five putative surface protein mutants tested, only a null mutation in thehmpref0536_10633gene, encoding a putative SDP with an LPxTG motif, resulted in a significant loss of adhesion to both Caco-2 cells and mucus. Complementation with the functional gene on a plasmid restored adhesion to Caco-2 cells. However, complete restoration of adhesion to mucus was not achieved. Overexpression ofhmpref0536_10633in strain ATCC PTA 6475 resulted in an increased adhesion to Caco-2 cells and mucus compared with the WT strain. We conclude from these results that, among the putative surface proteins tested, the protein encoded byhmpref0536_10633plays a critical role in binding ofLactobacillus reuteriATCC PTA 6475 to Caco-2 cells and mucus. Based on this, we propose that this LPxTG motif containing protein should be referred to as cell and mucus binding protein A (CmbA).
Cytoplasmic nanojunctions between lysosomes and sarcoplasmic reticulum are required for specific calcium signaling
Authors: Fameli Nicola , Ogunbayo Oluseye A. , van Breemen Cornelis , Evans A. Mark
Published: January 2014

Herein we demonstrate how nanojunctions between lysosomes and sarcoplasmic reticulum (L-SR junctions) serve to couple lysosomal activation to regenerative, ryanodine receptor-mediated cellular Ca2+waves. In pulmonary artery smooth muscle cells (PASMCs) it has been proposed that nicotinic acid adenine dinucleotide phosphate (NAADP) triggers increases in cytoplasmic Ca2+via L-SR junctions, in a manner that requires initial Ca2+release from lysosomes and subsequent Ca2+-induced Ca2+release (CICR) via ryanodine receptor (RyR) subtype 3 on the SR membrane proximal to lysosomes. L-SR junction membrane separation has been estimated to be<400 nm and thus beyond the resolution of light microscopy, which has restricted detailed investigations of the junctional coupling process. The present study utilizes standard and tomographic transmission electron microscopy to provide a thorough ultrastructural characterization of the L-SR junctions in PASMCs. We show that L-SR nanojunctions are prominent features within these cells and estimate that the junctional membrane separation and extension are about 15 nm and 300 nm, respectively. Furthermore, we develop a quantitative model of the L-SR junction using these measurements, prior kinetic and specific Ca2+signal information as input data. Simulations of NAADP-dependent junctional Ca2+transients demonstrate that the magnitude of these signals can breach the threshold for CICR via RyR3. By correlation analysis of live cell Ca2+signals and simulated Ca2+transients within L-SR junctions, we estimate that “trigger zones” with a 60–100 junctions are required to confer a signal of similar magnitude. This is compatible with the 130 lysosomes/cell estimated from our ultrastructural observations. Most importantly, our model shows that increasing the L-SR junctional width above 50 nm lowers the magnitude of junctional [Ca2+] such that there is a failure to breach the threshold for CICR via RyR3. L-SR junctions are therefore a pre-requisite for efficient Ca2+signal coupling and may contribute to cellular function in health and disease.
Genome-wide DNA methylome analysis reveals novel epigenetically dysregulated non-coding RNAs in human breast cancer
Authors: Li Yongsheng , Zhang Yunpeng , Li Shengli , Lu Jianping , Chen Juan , Zhao Zheng , Bai Jing , Xu Juan , Li Xia
Published: January 2014

The development of human breast cancer is driven by changes in the genetic and epigenetic landscape of the cell. Despite growing appreciation of the importance of epigenetics in breast cancers, our knowledge of epigenetic alterations of non-coding RNAs (ncRNAs) in breast cancers remains limited. Here, we explored the epigenetic patterns of ncRNAs in breast cancers via a sequencing-based comparative methylome analysis, mainly focusing on two most popular ncRNA biotypes, long non-coding RNAs (lncRNAs) and miRNAs. Besides global hypomethylation and extensive CpG islands (CGIs) hypermethylation, we observed widely aberrant methylation in the promoters of ncRNAs, which was higher than that of protein-coding genes. Specifically, intergenic ncRNAs were observed to contribute a large slice of the aberrantly methylated ncRNA promoters. Moreover, we summarized five patterns of ncRNA promoter aberrant methylation in the context of genomic CGIs, where aberrant methylation occurred not only on the CGIs, but also flanking regions and CGI sparse promoters. Integration with transcriptional datasets, we found that the ncRNA promoter methylation events were associated with transcriptional changes. Furthermore, a panel of ncRNAs were identified as biomarkers that were able to discriminate between disease phenotypes (AUCs>0.90). Finally, the potential functions for aberrantly methylated ncRNAs were predicted based on similar patterns, adjacency and/or target genes, highlighting that ncRNAs and coding genes coordinately mediated pathways dysregulation in the development and progression of breast cancers. This study presents the aberrant methylation patterns of ncRNAs, which will be a highly valuable resource for investigations at understanding epigenetic regulation of breast cancers.

[Supplemental material is available online atwww.genome.org.]
Remarkable Reproducibility of Enzyme Activity Profiles in Tomato Fruits Grown under Contrasting Environments Provides a Roadmap for Studies of Fruit Metabolism
Authors: Biais Benoît , Bénard Camille , Beauvoit Bertrand , Colombié Sophie , Prodhomme Duyên , Ménard Guillaume , Bernillon Stéphane , Gehl Bernadette , Gautier Hélène , Ballias Patricia , Mazat Jean-Pierre , Sweetlove Lee , Génard Michel , Gibon Yves
Published: January 2014

To assess the influence of the environment on fruit metabolism, tomato (Solanum lycopersicum ‘Moneymaker’) plants were grown under contrasting conditions (optimal for commercial, water limited, or shaded production) and locations. Samples were harvested at nine stages of development, and 36 enzyme activities of central metabolism were measured as well as protein, starch, and major metabolites, such as hexoses, sucrose, organic acids, and amino acids. The most remarkable result was the high reproducibility of enzyme activities throughout development, irrespective of conditions or location. Hierarchical clustering of enzyme activities also revealed tight relationships between metabolic pathways and phases of development. Thus, cell division was characterized by high activities of fructokinase, glucokinase, pyruvate kinase, and tricarboxylic acid cycle enzymes, indicating ATP production as a priority, whereas cell expansion was characterized by enzymes involved in the lower part of glycolysis, suggesting a metabolic reprogramming to anaplerosis. As expected, enzymes involved in the accumulation of sugars, citrate, and glutamate were strongly increased during ripening. However, a group of enzymes involved in ATP production, which is probably fueled by starch degradation, was also increased. Metabolites levels seemed more sensitive than enzymes to the environment, although such differences tended to decrease at ripening. The integration of enzyme and metabolite data obtained under contrasting growth conditions using principal component analysis suggests that, with the exceptions of alanine amino transferase and glutamate and malate dehydrogenase and malate, there are no links between single enzyme activities and metabolite time courses or levels.
The geometry of Niggli reduction:SAUC– search of alternative unit cells
Authors: McGill Keith J. , Asadi Mojgan , Karakasheva Maria T. , Andrews Lawrence C. , Bernstein Herbert J.
Published: January 2014

A database of lattices using theG6representation of the Niggli-reduced cell as the search key provides a more robust and complete search than older techniques. Searching is implemented by finding the distance from the probe cell to other cells using a topological embedding of the Niggli reduction inG6, so that all cells representing similar lattices will be found. The embedding provides the first fully linear measure of distances between unit cells. Comparison of results with those from older cell-based search algorithms suggests significant value in the new approach.
A large-area CMOS detector for high-energy synchrotron powder diffraction and total scattering experiments
Authors: Abdala Paula Macarena , Mauroy Henrik , van Beek Wouter
Published: January 2014

A complementary metal-oxide semiconductor (CMOS) detector with an active area of 290.8 × 229.8 mm has been evaluated for X-ray scattering experiments at energies between 20 and 50 keV. Detector calibration and integration procedures are discussed in addition to the determination of the linearity, angular resolution and energy response of the detector in the context of its envisaged use. Data on reference compounds and samples with different crystallinity were collected and analysed with classical Rietveld and pair distribution function refinements. Comparisons with literature and high-resolution data from the same beamline demonstrate that the presented detector is suitable for crystallographic and total scattering experiments.
Defective barrier function accompanied by structural changes of psoriatic stratum corneum
Authors: Takahashi Hidetoshi , Tsuji Hitomi , Minami‐Hori Masako , Miyauchi Yuki , Iizuka Hajime
Published: January 2014

Although barrier function of psoriatic skin is shown to be decreased by measuring transepidermal water loss (TEWL), few reports exist examining other physical skin properties and components including stratum corneum hydration, natural moisturizing factor (NMF), free fatty acids (FFA), β‐sheet and α‐helix ratio of structural protein(s), and sebum content. We compared the skin properties and components of normal, involved and uninvolved skin of psoriasis. Using a corneometer and attenuated total reflection‐infrared spectrometer, we measured TEWL, stratum corneum hydration, NMF, FFA, β/α ratio and sebum in psoriasis vulgaris patients and healthy controls. TEWL and β/α ratio of involved psoriatic skin were significantly increased compared with uninvolved skin and normal control skin. In contrast, stratum corneum hydration, NMF and FFA, but not sebum, are significantly decreased in the involved skin compared with uninvolved skin and normal skin. TEWL and stratum corneum hydration returned to the normal levels following clinical improvement of the lesion. Barrier function and hydration of psoriatic skin are defective and secondary structure in stratum corneum protein is altered in the involved psoriatic skin.
Raptors as surrogates of biodiversity along a landscape gradient
Authors: Burgas Daniel , Byholm Patrik , Parkkima Tiina
Published: January 2014

With biodiversity facing threats, there is a need to improve reserve selection procedures. However, detailed information about different biodiversity measures (e.g. species richness) at potential sites is often lacking, and selecting areas that protect most biodiversity is difficult. To simplify matters, biodiversity surrogate species, that is, species associated with higher biodiversity than average, have been used for area selection. However, consensus about the performance of the surrogate species concept is lacking, and there are few studies investigating potential differences in the effectiveness of multiple predators as surrogates for biodiversity over large spatial scales.

We evaluated two avian predators, the northern goshawk Accipiter gentilis and the Ural owl Strix uralensis, as surrogates for biodiversity in the boreal forest biome in Western Finland. We used a study design including nest sites and two reference sites for each nest, the diversity of birds and wood‐decaying fungi (polypores). We assessed simultaneously whether surrogacy persisted at the landscape level while moving from one vegetation zone to another.

We generally found more birds and polypores around the nest sites for both goshawks and Ural owls than at their respective reference sites. However, the goshawk outperformed the Ural owl.

Additionally, although biodiversity was found to decrease at the landscape scale as a result of a decrease in vegetation complexity with increasing longitude, the surrogacy efficiency of the raptors remained unchanged.

Synthesis and applications. These findings suggest that the surrogate species concept applied to raptors may be an efficient addition to methods for identifying areas of conservation priority, even across vegetation zones. We conclude that protecting areas around raptor nests is a method to consider in order to halt forest biodiversity loss. Finally, sampling biodiversity along diversity and landscape gradients can improve the necessary assessment of surrogate species.
Antibiotic treatments and microbes in the gut
Authors: Macfarlane Sandra
Published: January 2014

Antibiotic therapies are important in combating disease‐causing microorganisms and maintaining host health. It is widely accepted that exposure of the gut microbiota to antibiotics can lead to decreased susceptibility and the development of multi‐drug‐resistant disease‐causing organisms, which can be a major clinical problem. It is also important to consider that antibiotics not only target pathogenic bacteria in the gut, but also can have damaging effects on the ecology of commensal species. This can reduce intrinsic colonization resistance and contribute to problems with antibiotic resistance, including lateral transfer of resistance genes. Our knowledge of the impact of antibiotic treatment on the ecology of the normal microbiota has been increased by recent advances in molecular methods and use of in vitro model systems to investigate the impact of antibiotics on the biodiversity of gut populations and the spread of antibiotic resistance. These highlight the need for more detailed structural and functional information on the long‐term antibiotic‐associated alterations in the gut microbiome, and spread of antibiotic resistance genes. This will be crucial for the development of strategies, such as targeted therapeutics, probiotics, prebiotics and synbiotics, to prevent perturbations in the gut microbiota, the restoration of beneficial species and improvements in host health.
Visa problem: certification, kinship, and the production of ‘ineligibility’ in the Gambia
Authors: Gaibazzi Paolo
Published: January 2014

The article describes the documentary vicissitudes of young Gambian men of Soninke ethnicity. Normally the most mobile subjects in a milieu where international migration is central to subsistence and prosperity, these young men often fail to secure entry visas to the West and other desirable destinations owing to restrictive admission policies. Would‐be travellers cope with high rejection rates, but also struggle to secure financial and logistical support from relatives in order to meet the demanding requirements of visa applications. Since kinship mediates access to travel documents, the article suggests that visa ineligibility is a product of both state‐based and societal practices of certification. It shows how the visa regime plays into the kinship reciprocities and affects that produce, discipline, and select prospective migrants, thereby transferring and concealing the arbitrariness and uncertainty of legal‐political structures of mobility.
The sociality of the wage: money rhythms, wealth circulation, and the problem with cash on the Zimbabwean‐South African border
Authors: Bolt Maxim
Published: January 2014

While wage labour and money have received much anthropological attention, the same cannot be said of wages themselves – actual banknotes and coins distributed in workforces. This article traces wages' social productivity among farm workers on the Zimbabwean‐South African border. In this migrant‐labour setting, money's form matters. Because currency objects are physically the same, it is difficult for workers to store them in an insecure environment, leading them to turn to one another. As they manage their earnings, workers attempt to establish themselves as social persons while maintaining future options in uncertain circumstances. Workforce ties both shape and are constituted by flows of cash and the rhythms and circuits of the wage. Seen in terms of form, wages are highly personal – the very stuff of sociality.
Enskillment inhibited: ‘industrial gardening’ in Britain
Authors: Gieser Thorsten
Published: January 2014

Horticulture – like many other traditional crafts in Britain – is said to suffer from a ‘skills problem’. A recent survey suggests that one of the reasons for this is increased outsourcing of horticultural work from public employers to private contractors. While anthropologists have generally acknowledged the politics of learning, they have had little to say about enskillment in work contexts which have been reconfigured in a way that leaves hardly any room for institutionalized methods of learning. Private gardening contractors are an example of such a work context, and in this article I scrutinize their practices to show the various ways in which enskillment is inhibited. Rather than referring to the concept of ‘deskilling’ – usually evoked in discussions of skills problems – I employ the notion of an inhibition of enskillment in order to emphasize that every feature that fosters skill also has a ‘shadow side’ to it which bears a potential to inhibit skill. Implicit in this argument is a critique of neoliberal work practices which shape enskillment as well as the natural environment.
Opposition to the Channel Tunnel, 1882–1975: Identity, Island Status and Security
Authors: Redford Duncan
Published: January 2014

This article will discuss the defence arguments that were used to oppose the channel tunnel, the relationship between these arguments and Britain's island status, the perceptions of British insularity, together with how and possibly why these changed in the period 1882–1975. The opposition to the Channel Tunnel project, especially in the period 1880 to 1945, can provide historians with a valuable insight into the British relationship with the sea. In particular, the opposition to a channel tunnel provides a way of analysing concepts of island status within Britain and what being an island meant to the British sense of self and identity, as they were expressed in the media as well as in official papers. At the same time, the changing attitudes to a channel tunnel, notably in the inter‐war period and the post‐1945 era, also show how the British understanding of what being an island state gave them in terms of security and identity changed. Such a change was as a result of new or improving technologies, particularly the aircraft, and the resulting impact it had on conceptions of security that being an island provided.
‘Not getting his meals in the kitchen’:LordActon's Quest for Public Office, 1892–1894
Authors: Otte T. G.
Published: January 2014

The historianLordActon is best known asLordRosebery's choice for the Regius Chair of Modern History atCambridgeUniversity in 1895. This outcome was not the inexorable culmination an historian's career. It was rather a form of compensation for the failure ofActon's earlier ambitions for political or public office. Drawing on hitherto largely untapped archival material this article re‐examines this crucial period in the final decade ofActon's life. To an extent, this is a study in failure.Acton's attempt to re‐enter public life remained abortive. But this study goes beyond adding to our understanding ofActon's biography. His quest for public office furnishes a useful prism to study also the prolonged post‐Gladstonian transition phase inLiberal politics in the middle part of the 1890s, its underlying ideological fissures and the problematic personal relations at the top of theLiberal Party.
Belonging to Bad: Ambiguity, Parramatta Girls and the Parramatta Girls Home
Authors: FRANKLIN CORRINNE
Published: January 2014

From 1887 to 1974, ‘corrupt’ adolescent girls were incarcerated in Parramatta Girls Home, a New South Wales state government facility charged with their ‘care and protection’. This paper examines the experiences of former inmates of Parramatta Girls Home (PGH) and explores their ongoing connections to the Home. Using the narratives of former inmates and submissions to public inquiries, the relationship that these women have with the Home and each other is explored. There is a strong thread of connection to place amongst former inmates, with their identity as ‘Parra girls’ shaping aspects of their post‐incarceration lives. For those women who were incarcerated at PGH, the connection to people and place focuses on the Home and is a powerful influence on their subsequent experiences of security and belonging.
The association of perioperative dexamethasone, smoking and alcohol abuse with wound complications after laparotomy
Authors: DAHL RIKKE M. , WETTERSLEV JØRN , JORGENSEN LARS N. , RASMUSSEN LARS S. , MOLLER ANN M. , MEYHOFF CHRISTIAN S. ,   PROXI TRIAL GROUP
Published: January 2014

Background

A number of perioperative risk factors may suppress the immune system and contribute to the development of post‐operative complications. The association between surgical site infection (SSI) and other wound‐related complications resulting from immunosuppression through either perioperative administration of dexamethasone, pre‐operative smoking or alcohol abuse is, however, uncertain.

Methods

This study was a post hoc analysis of data from the PROXI randomized trial in 1386 patients who underwent emergency or elective laparotomy. We assessed the associations of use of dexamethasone, smoking status and alcohol abuse with the primary outcome, being a composite of SSI, anastomotic leak, wound dehiscence, burst abdomen and 30‐day mortality.

Results

The primary outcome occurred in 21% of patients receiving dexamethasone versus 28% of patients not receiving dexamethasone, and this was not statistically significant when adjusting for stratification variables originally used in the PROXI trial [OR 0.90, 95% CI (0.65–1.24)]. In smokers, the primary outcome occurred in 32%, compared with 23% of non‐smokers (P = 0.0001). Smokers also had a higher frequency of SSI (25% vs 17%, P < 0.0001) and burst abdomen (3.8% vs 2.4%, P = 0.04). In alcohol abusers, the primary outcome occurred in 48%, compared with 25% in patients who did not abuse alcohol (P = 0.0006). Burst abdomen occurred more commonly in alcohol abusers (15% vs 2.3%, P < 0.0001).

Conclusion

Perioperative administration of dexamethasone was not significantly associated with SSI or other wound‐related complications. Conversely, smoking and alcohol abuse were both significant predictors of the primary outcome consisting of wound‐related complications and mortality.
Longitudinal variance of visceral fat thickness in pregnant adolescents
Authors: Dutra Luciana P. , Cisneiros Rosangela M. , Souza Alex S. , Diniz Carolina P. , Moura Laísla A. , Figueiroa Jose N. , Alves João G. B.
Published: January 2014

This study aims to investigate the longitudinal change in visceral fat thickness (VFT) during normal pregnancy. A prospective cohort study with 75 primiparous adolescents was carried out in Petrolina, Brazil. VFT was evaluated by ultrasound between 12–20 weeks gestation and immediately after delivery. We noted a statistically significant increase in VFT; 1.3 cm ± 1.0. No correlation was found between VFT and maternal anthropometric variables. VFT increases about 30% from the first to the second half of pregnancy in primiparous adolescents.
High‐resolution microarray in the assessment of fetal anomalies detected by ultrasound
Authors: Charan Poonam , Woodrow Nicole , Walker Sue P. , Ganesamoorthy Devika , McGillivray George , Palma‐Dias Ricardo
Published: January 2014

Aims

The main aim of this study was to determine the feasibility of using high‐resolution microarray to assist with prenatal diagnosis of ultrasound‐detected fetal abnormality and to describe the frequency of abnormal results in different categories of fetal anomalies.

Methods

Prospective cross‐sectional study was conducted on women diagnosed with a fetal anomaly (ies) between February 2009 and December 2011 who were offered testing by microarray analysis (Affymetrix 2.7M SNP) and fluorescent in situ hybridisation (FISH) instead of standard karyotyping. Fetal anomalies were categorised according to organ system involvement.

Results

One hundred and eighteen women consented to testing with microarray. Eleven of one hundred eighteen (9.3%) cases had aneuploidy detected by FISH. Of the remaining 107, 23 (21.5%) had an abnormality detected on microarray, only three of which would have been detected using the combination of six‐probe FISH and banded karyotype. The maximum expected yield for six‐probe FISH and karyotype was thus 14/118 (11.8%), compared to 34/118 (28.8%), P < 0.0001. Of the 23 abnormalities detected with microarray, 10 (43%) were pathogenic, six (26%) were long continuous stretches of homozygosity and seven (30%) were of uncertain significance. The maximum yield was in cases with cardiovascular (100%); multiple (40%); central nervous system (CNS) (25%) and skeletal (9%) abnormalities.

Conclusion

This study has confirmed the feasibility of translation of microarray into clinical practice. 11.8% (14/118) of the cases would have a genetic basis of an abnormality with a FISH and banded karyotype. This figure is approximately tripled to 28.8% (34/118) if we offer FISH and microarray. High yield for imbalances are multiple, cardiovascular, CNS and skeletal abnormalities.
The role of endometrial thickness for detecting endometrial pathologies in asymptomatic postmenopausal women
Authors: Saatli Bahadir , Yildirim Nuri , Olgan Safak , Koyuncuoglu Meral , Emekci Ozlen , Saygılı Ugur
Published: January 2014

Background

The aim of the present study was to evaluate the significance of endometrial sampling in asymptomatic, bleeding‐free postmenopausal women who have endometrial thickness greater or equal to 5 mm.

Methods

A retrospective review was conducted of all women who underwent transvaginal ultrasonography between January 2000 and March 2009 in a menopause clinic, who were found to have an endometrial thickness of at least 5 mm and who were subjected to endometrial sampling.

Results

Five hundred and thirty asymptomatic postmenopausal women underwent ultrasonographic evaluation with subsequent endometrial sampling. The mean endometrial stripe thickness was 8.7 mm (range: 6–26). Five cases of adenocarcinoma (0.9%) and 65 (12.2%) cases of simple/complex atypical hyperplasia were diagnosed.

Conclusions

In this study, 106 investigations were performed to detect one case of adenocarcinoma. Although this is a high number per case detection of endometrial adenocarcinoma, considering the rising incidence of endometrial cancer, large prospective trials with surrogate criteria for asymptomatic women are needed to investigate the importance of thickened endometrial stripe in postmenopausal women.
Streptomyces cyaneus dermatitis in a dog
Authors: Nicholls PK , Allen G , Irwin PJ
Published: January 2014

Background

A nearly 4‐year‐old neutered male Australian Terrier was referred for a nodular pyogranulomatous mass of the right axilla. It had been poorly responsive to antibiotic therapy.

Case report

Based on filamentous Gram‐positive organisms identified in earlier biopsy material, infection by an Actinomyces sp. was suspected and the dog showed clinical improvement on a trial of potentiated sulfonamides. Recurrence 5 months later prompted euthanasia, with Streptomyces cyaneus being cultured and confirmed by genetic sequencing of part of the 16 s ribosomal RNA gene.

Conclusion

Invasive Streptomyces spp. infections are uncommon in humans and animals, and isolations are sometimes considered to be contaminants, but the demonstration of the organism within the lesion in this instance indicates that the isolation of a Streptomyces sp. from veterinary cases should not always be considered as contamination, because this genus is clearly pathogenic.
Use of REP‐PCR and 16S rRNA gene sequencing for comparison of Mannheimia haemolytica isolates obtained from fatal cases of bovine respiratory disease in the USA and Australia
Authors: Taylor JD , Doyle DJ , Blackall PJ , Confer AW
Published: January 2014

Objective

Assess the variability of Mannheimia haemolytica isolates obtained from fatal cases of bovine respiratory disease (BRD) in the USA and Australia using repetitive sequence‐based PCR (REP‐PCR) and sequencing of the 16S ribosomal RNA (rRNA) gene.

Methods

We examined 22 isolates from the USA and 36 isolates from Australia using (GTG)5 and BOX‐A1R REP‐PCR primers, as well as sequencing a 700‐base pair length of the 16S rRNA gene. The discriminatory ability of each typing method was assessed and correlation coefficients were calculated to assess concordance between the results of each approach.

Results

All methods appeared to discriminate among isolates, with BOX‐A1R being the most sensitive and sequencing the least sensitive. Modest to moderate diversity was seen among the isolates, with as much variation within a continent as between the two.

Conclusions

Using samples from diverse origins may permit extrapolation even to isolates with distant geographic and temporal relationships. Further, this information can serve as a baseline in assessing whether M. haemolytica is an opportunistic pathogen or if there are notable features that distinguish commensal isolates from those more likely to be associated with disease.
An Update to Returning Genetic Research Results to Individuals: Perspectives of the Industry Pharmacogenomics Working Group
Authors: Prucka Sandra K. , Arnold Lester J. , Brandt John E. , Gilardi Sandra , Harty Lea C. , Hong Feng , Malia Joanne , Pulford David J.
Published: January 2014

The ease with which genotyping technologies generate tremendous amounts of data on research participants has been well chronicled, a feat that continues to become both faster and cheaper to perform. In parallel to these advances come additional ethical considerations and debates, one of which centers on providing individual research results and incidental findings back to research participants taking part in genetic research efforts. In 2006 the Industry Pharmacogenomics Working Group (I‐PWG) offered some ‘Points‐to‐Consider’ on this topic within the context of the drug development process from those who are affiliated to pharmaceutical companies. Today many of these points remain applicable to the discussion but will be expanded upon in this updated viewpoint from the I‐PWG. The exploratory nature of pharmacogenomic work in the pharmaceutical industry is discussed to provide context for why these results typically are not best suited for return. Operational challenges unique to this industry which cause barriers to returning this information are also explained.
The Impact of Recession on Adult Training: Evidence from the United Kingdom in 2008–2009
Authors: Mason Geoff , Bishop Kate
Published: January 2014

Analysis of longitudinal data from Employers Skills Updating Surveys in the United Kingdom suggests that in many establishments training plans were blown off course by the 2008–2009 recession, with reduced coverage of adult training and especially of off‐the‐job training. The effects of such cutbacks on skill levels have been partially alleviated by more precise targeting of on‐the‐job training on meeting skills improvement needs. However, in a sizeable proportion of establishments, future productivity and competitiveness are likely to be impaired by failure to upgrade adult workers' skills to standards which employers themselves perceived as necessary prior to the recession.
Phase III, randomised, double‐blind, placebo‐controlled study of the β3‐adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder
Authors: Yamaguchi Osamu , Marui Eiji , Kakizaki Hidehiro , Homma Yukio , Igawa Yasuhiko , Takeda Masayuki , Nishizawa Osamu , Gotoh Momokazu , Yoshida Masaki , Yokoyama Osamu , Seki Narihito , Ikeda Yasushi , Ohkawa Sumito
Published: January 2014

Objective

To evaluate the efficacy and safety of the β3‐adrenoceptor agonist mirabegron, in a Japanese population with overactive bladder (OAB).

Patients and Methods

This randomised, double‐blind, placebo‐controlled phase III study enrolled adult patients experiencing OAB symptoms for ≥24 weeks. Patients with ≥ 8 micturitions/24 h and ≥1 urgency episode/24 h or ≥1 urgency incontinence episode/24 h were randomised to once‐daily placebo, mirabegron 50 mg or tolterodine 4 mg (as an active comparator, without testing for non‐inferiority of efficacy and safety) for 12 weeks.

The primary endpoint was the change in the mean number of micturitions/24 h from baseline to final assessment. Secondary endpoints included micturition variables related to urgency and/or incontinence and quality‐of‐life domain scores on the King's Health Questionnaire.

Safety assessments included adverse events (AEs), post‐void residual urine volume, laboratory variables, vital signs and 12‐lead electrocardiogram.

Results

A total of 1139 patients were randomised to receive placebo (n = 381), mirabegron 50 mg (n = 380) or tolterodine 4 mg (n = 378). Demographic and baseline characteristics were similar among the treatment groups.

At final assessment, mirabegron was significantly superior to placebo in terms of mean [sd] change from baseline in number of micturitions/24 h (–1.67 [2.212] vs ‐0.86 [2.354]; P < 0.001) and mean [sd] change from baseline in number of urgency episodes/24 h (–1.85 [2.555] vs –1.37 [3.191]; P = 0.025), incontinence episodes/24 h (–1.12 [1.475] vs –0.66 [1.861]; P = 0.003), urgency incontinence episodes/24 h (–1.01 [1.338] vs –0.60 [1.745]; P = 0.008), and volume voided/micturition (24.300 [35.4767] vs 9.715 [29.0864] mL; P < 0.001).

The incidence of AEs in the mirabegron group was similar to that in the placebo group. Most AEs were mild and none were severe.

Conclusions

Mirabegron 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.
One‐ vs 4‐week stent placement after laparoscopic and robot‐assisted pyeloplasty: results of a prospective randomised single‐centre study
Authors: Danuser H. , Germann C. , Pelzer N. , Rühle A. , Stucki P. , Mattei A.
Published: January 2014

Objectives

To determine whether 1‐week stenting of the pelvi‐ureteric anastomosis of laparoscopic or robot‐assisted pyeloplasty is as effective as 4‐week stenting, based on their respective success rates.

Patients and Methods

A total of 100 patients with pelvi‐ureteric junction obstruction were treated by Anderson‐Hynes pyeloplasty and the anastomosis was stented using a 6‐F JJ catheter for either 1 week (1W series) or 4 weeks (4W series), based on a randomisation protocol. Postoperative follow‐up was performed at 3 months using intravenous urography (IVU), at 6 months using diuretic renography and at 1, 3 and 5 years using ultrasonography. Statistical analysis was performed using a one‐sided Z‐test, Pearsons's chi‐squared test and a Wilcoxon rank sum test.

Results

The primary outcome measure, success rate, which was defined as no obstruction on IVU and diuretic renography, was 100% in the 1W series and not inferior to the success rate of 98% in the 4W series (P = 0.006). The following secondary outcome measures were not significantly different between the 1W and the 4W series with regard to residual symptoms (10 vs 6%; P = 0.48), rate of complications (4 vs 6%; P = 0.65), need for synchronous robot‐assisted pyelolithotomy (4 vs 8%; P = 0.47), improvement in split renal function (1 vs 0%; P = 0.59) and duration of surgery (200 vs 192 min; P = 0.87). Only length of hospital stay was significantly different; this was shorter in the 1W series (5 vs 6 days; P = 0.01).

Conclusions

Stenting of the pelvi‐ureteric anastomosis after laparoscopic or robot‐assisted pyeloplasty for 1 week is as effective as stenting for 4 weeks. Both procedures, laparoscopic or robot‐assisted pyeloplasty have an excellent success rate.
Representing How Rabbits Quack and Competitors Act: Limits on Preschoolers' Efficient Ability to Track Perspective
Authors: Low Jason , Drummond William , Walmsley Andrew , Wang Bo
Published: January 2014

This study investigated whether humans have two mind‐reading systems whereby the efficient system, unlike the flexible system, is naturally limited. There were two experiments and the first included adults as well as children (3‐ to 4‐year‐olds; totalN = 128). In Experiment 1, all groups efficiently gazed in anticipation of an agent's beliefs about object location but not object identity (an ambiguous figure). In Experiment 2, children showed limits in anticipating a competitive agent's action in terms of his perspective on what is desirable. Flexibility in verbally predicting agents' actions across contexts developed with age. Convergence on signature limits across different ages and methods suggests that indirect anticipations involve minimal mind reading, whereas direct predictions tap a refined understanding of perspective.