bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific immune priming in the invasive ctenophore
Mnemiopsis leidyi
Authors: Bolte Sören , Roth Olivia , Philipp Eva E. R. , Saphörster Julia , Rosenstiel Philip , Reusch Thorsten B. H.
Published: November 2013

Specific immune priming enables an induced immune response upon repeated pathogen encounter. As a functional analogue to vertebrate immune memory, such adaptive plasticity has been described, for instance, in insects and crustaceans. However, towards the base of the metazoan tree our knowledge about the existence of specific immune priming becomes scattered. Here, we exposed the invasive ctenophore
Mnemiopsis leidyi
repeatedly to two different bacterial epitopes (Gram-positive or -negative) and measured gene expression. Ctenophores experienced either the same bacterial epitope twice (homologous treatments) or different bacterial epitopes (heterologous treatments). Our results demonstrate that immune gene expression depends on earlier bacterial exposure. We detected significantly different expression upon heterologous compared with homologous bacterial treatment at three immune activator and effector genes. This is the first experimental evidence for specific immune priming in Ctenophora and generally in non-bilaterian animals, hereby adding to our growing notion of plasticity in innate immune systems across all animal phyla.
Unveiling a mechanism for species decline in fragmented habitats: fragmentation induced reduction in encounter rates
Authors: Wosniack M. E. , Santos M. C. , Pie M. R. , Marques M. C. M. , Raposo E. P. , Viswanathan G. M. , da Luz M. G. E.
Published: November 2013

Several studies have reported that fragmentation (e.g. of anthropogenic origin) of habitats often leads to a decrease in the number of species in the region. An important mechanism causing this adverse ecological impact is the change in the encounter rates (i.e. the rates at which individuals meet other organisms of the same or different species). Yet, how fragmentation can change encounter rates is poorly understood. To gain insight into the problem, here we ask how landscape fragmentation affects encounter rates when all other relevant variables remain fixed. We present strong numerical evidence that fragmentation decreases search efficiencies thus encounter rates. What is surprising is that it falls even when the global average densities of interacting organisms are held constant. In other words, fragmentationper secan reduce encounter rates. As encounter rates are fundamental for biological interactions, it can explain part of the observed diminishing in animal biodiversity. Neglecting this effect may underestimate the negative outcomes of fragmentation. Partial deforestation and roads that cut through forests, for instance, might be responsible for far greater damage than thought. Preservation policies should take into account this previously overlooked scientific fact.
Assessing the effect of dynamics on the closed-loop protein-folding hypothesis
Authors: Chintapalli Sree V. , Illingworth Christopher J. R. , Upton Graham J. G. , Sacquin-Mora Sophie , Reeves Philip J. , Mohammedali Hani S. , Reynolds Christopher A.
Published: November 2013

The closed-loop (loop-n-lock) hypothesis of protein folding suggests that loops of about 25 residues, closed through interactions between the loop ends (locks), play an important role in protein structure. Coarse-grain elastic network simulations, and examination of loop lengths in a diverse set of proteins, each supports a bias towards loops of close to 25 residues in length between residues of high stability. Previous studies have established a correlation between total contact distance (TCD), a metric of sequence distances between contacting residues (cf. contact order), and the log-folding rate of a protein. In a set of 43 proteins, we identify an improved correlation (
r
2
= 0.76), when the metric is restricted to residues contacting the locks, compared to the equivalent result when all residues are considered (
r
2
= 0.65). This provides qualified support for the hypothesis, albeit with an increased emphasis upon the importance of a much larger set of residues surrounding the locks. Evidence of a similar-sized protein core/extended nucleus (with significant overlap) was obtained from TCD calculations in which residues were successively eliminated according to their hydrophobicity and connectivity, and from molecular dynamics simulations. Our results suggest that while folding is determined by a subset of residues that can be predicted by application of the closed-loop hypothesis, the original hypothesis is too simplistic; efficient protein folding is dependent on a considerably larger subset of residues than those involved in lock formation.
Role of different factors affecting interdiffusion in Cu(Ga) and Cu(Si) solid solutions
Authors: Santra Sangeeta , Dong Hongqun , Laurila Tomi , Paul Aloke
Published: November 2013

A detailed diffusion study was carried out on Cu(Ga) and Cu(Si) solid solutions in order to assess the role of different factors in the behaviour of the diffusing components. The faster diffusing species in the two systems, interdiffusion, intrinsic and impurity diffusion coefficients, are determined to facilitate the discussion. It was found that Cu was more mobile in the Cu–Si system, whereas Ga was the faster diffusing species in the Cu–Ga system. In both systems, the interdiffusion coefficients increased with increasing amount of solute (e.g. Si or Ga) in the matrix (Cu). Impurity diffusion coefficients for Si and Ga in Cu, found out by extrapolating interdiffusion coefficient data to zero composition of the solute, were both higher than the Cu tracer diffusion coefficient. These observed trends in diffusion behaviour could be rationalized by considering: (i) formation energies and concentration of vacancies, (ii) elastic moduli (indicating bond strengths) of the elements and (iii) the interaction parameters and the related thermodynamic factors. In summary, we have shown here that all the factors introduced in this paper should be considered simultaneously to understand interdiffusion in solid solutions. Otherwise, some of the aspects may look unusual or even impossible to explain.
Evolution of anisotropy in soft tissue
Authors: Murphy J. G.
Published: November 2013

The phenomenological approach to the modelling of the mechanical response of arteries usually assumes a reduced form of the strain-energy function in order to reduce the mathematical complexity of the model. A common approach eschews the full basis of seven invariants for the strain-energy function in favour of a reduced set of only three invariants. It is shown that this reduced form is not consistent with the corresponding full linear theory based on infinitesimal strains. It is proposed that compatibility with the linear theory is an essential feature of any nonlinear model of arterial response. Two approaches towards ensuring such compatibility are proposed. The first is that the nonlinear theory reduces to the full six-constant linear theory, without any restrictions being imposed on the constants. An alternative modelling strategy whereby an anisotropic material is compatible with a simpler material in the linear limit is also proposed. In particular, necessary and sufficient conditions are obtained for a nonlinear anisotropic material to be compatible with an isotropic material for infinitesimal deformations. Materials that satisfy these conditions should be useful in the modelling of the crimped collagen fibres in the undeformed configuration.
Immunostimulatory CpG motifs in the genomes of gut bacteria and their role in human health and disease
Authors: Kant Ravi , de Vos Willem M. , Palva Airi , Satokari Reetta
Published: November 2013

Toll-like receptor (TLR) signalling plays an important role in epithelial and immune cells of the intestine. TLR9 recognizes unmethylated CpG motifs in bacterial DNA, and TLR9 signalling maintains the gut epithelial homeostasis. Here, we carried out a bioinformatic analysis of the frequency of CpG motifs in the genomes of gut commensal bacteria across major bacterial phyla. The frequency of potentially immunostimulatory CpG motifs (all CpG hexamers) or purine-purine-CG-pyrimidine-pyrimidine hexamers was linearly dependent on the genomic G+C content. We found that species belonging toProteobacteria,BacteroidetesandActinobacteria(including bifidobacteria) carried high counts of GTCGTT, the optimal motif stimulating human TLR9. We also found thatEnterococcus faecalis,Lactobacillus casei,Lactobacillus plantarumandLactobacillus rhamnosus, whose strains have been marketed as probiotics, had high counts of GTCGTT motifs. As gut bacterial species differ significantly in their genomic content of CpG motifs, the overall load of CpG motifs in the intestine depends on the species assembly of microbiota and their cell numbers. The optimal CpG motif content of microbiota may depend on the host’s physiological status and, consequently, on an adequate level of TLR9 signalling. We speculate that microbiota with increased numbers of microbes with CpG motif-rich DNA could better support mucosal functions in healthy individuals and improve the T-helper 1 (Th1)/Th2 imbalance in allergic diseases. In autoimmune disorders, CpG motif-rich DNA could, however, further increase the Th1-type immune responsiveness. Estimation of the load of microbe-associated molecular patterns, including CpG motifs, in gut microbiota could shed new light on host–microbe interactions across a range of diseases.
Highly efficient gene knockout in mice and zebrafish with RNA-guided endonucleases
Authors: Sung Young Hoon , Kim Jong Min , Kim Hyun-Taek , Lee Jaehoon , Jeon Jisun , Jin Young , Choi Jung-Hwa , Ban Young Ho , Ha Sang-Jun , Kim Cheol-Hee , Lee Han-Woong , Kim Jin-Soo
Published: November 2013

RNA-guided endonucleases (RGENs), derived from the prokaryotic Type II CRISPR-Cas system, enable targeted genome modification in cells and organisms. Here we describe the establishment of gene-knockout mice and zebrafish by the injection of RGENs as Cas9 protein:guide RNA complexes or Cas9 mRNA plus guide RNA into one-cell-stage embryos of both species. RGENs efficiently generated germline transmittable mutations in up to 93% of newborn mice with minimal toxicity. RGEN-induced mutations in the mouse Prkdc gene that encodes an enzyme critical for DNA double-strand break repair resulted in immunodeficiency both in F0 and F1 mice. We propose that RGEN-mediated mutagenesis in animals will greatly expedite the creation of genetically engineered model organisms, accelerating functional genomic research.
Giant condyloma acuminatum of Buschke–Lowenstein tumour: Disease development between 2000 and 2010
Authors: Safi Farouk , Bekdache Omar , Al‐Salam Suhail , Alashari Mouied , Mazen Taha
Published: November 2013

Aim

Giant condyloma acuminatum, originally described by Buschke and Lowenstein in 1925 as a lesion of the penis, is more rarely seen in the anorectum, and is characterized by clinical malignancy in the face of histological benignity; however, malignant transformation in approximately one‐third of patients to invasive squamous cell carcinoma has been described. Malignant transformation has been reported in patients with ‘ordinary’ condylomata acuminata as well. Human papillomavirus, known to cause condylomata acuminata, is also known to induce these tumours, and was found in 96 per cent of the 63 cases reviewed in the past 10 years. Radical R0 excision, independent of used surgical methods, as well as vigilant follow up, provides hope for cure. Conservative and/or multimodal therapy has been demonstrated in a few cases; however, its effect is not yet clear.

Patients and Methods

In the present study, we reviewed literature published between 2000 and 2010 and compared these with previous reviews.

Results

We found an increase in published cases per year of giant condyloma acuminatum. Sex ratios (3:1, male : female), mean age (42 years) and symptoms were found to be equal in this and previous reviews.

Conclusions

Our research found that there were more viral studies on specimens in order to understand the disease, and a less transformation rate to malignancy was found. Surgery is still the preferred practice for treating patients.
Ultrasound Evaluation of the Effects of Leukocytapheresis on Rheumatoid Arthritis
Authors: Yoshida Shuzo , Takeuchi Tohru , Maeda Yoichiro , Kimura Yuko , Hata Kenichiro , Hiramatsu Yuri , Shoda Takeshi , Makino Shigeki , Hanafusa Toshiaki , Shibahara Nobuhisa
Published: November 2013

Leukocytapheresis (LCAP) is effective in treating rheumatoid arthritis (RA). Ultrasound (US) examination of joints is useful for evaluating disease activity and therapeutic effects in RA, but the clinical assessment of LCAP therapy with US has been little reported. We investigated the usefulness of US for evaluating the effects of LCAP in patients with RA. US examination was performed in six patients (total of seven cases) who underwent LCAP. Twenty‐eight joints (bilateral shoulders, elbows, wrists, 1st to 5th metacarpophalangeal joints, 1st to 5th proximal interphalangeal joints, and knee joints) were evaluated by a systematic multiplanar grey‐scale and power Doppler (PD) examination. Disease activity of RA was evaluated using the 28‐joint Disease Activity Score with erythrocyte sedimentation rate (DAS28‐ESR). Moderate or good responses to LCAP based on the DAS28‐ESR were observed in four of the seven cases although C‐reactive protein (CRP) and ESR did not decrease. LCAP significantly reduced the mean total PD score 17.3 ± 11.6 to 13.0 ± 10.5 (P = 0.0469). The total PD score decreased in six of the seven cases, and the number of joints with PD score ≥2 decreased in five of the seven cases. The rate of decrease in the number of joints with PD score ≥2 correlated strongly with the DAS28‐ESR and its components, especially swollen joint counts and evaluator's global assessment, but not with the rate of decrease in CRP and ESR. US imaging of joints may be useful for evaluating the therapeutic effects of LCAP on RA compared to other inflammatory parameters.
Making It Personal: Regime Type and Nuclear Proliferation
Authors: Way Christopher , Weeks Jessica L. P.
Published: November 2013

Study after study has found that regime type has little or no effect on states’ decisions to pursue nuclear weapons. We argue, however, that conventional approaches comparing the behavior of democracies to that of nondemocracies have resulted in incorrect inferences. We disaggregate types of nondemocracies and argue that leaders of highly centralized, “personalistic” dictatorships are particularly likely to view nuclear weapons as an attractive solution to their concerns about regime security and face fewer constraints in pursuing nuclear weapons than leaders of other types of regimes. Combining our more nuanced classification of regime type with a more theoretically appropriate empirical approach, we find that personalist regimes are substantially more likely to pursue nuclear weapons than other regime types. This finding is robust to different codings of proliferation dates and a range of modeling approaches and specifications and has significant implications for both theory and policy.
Inhibition of Microbial Growth on Chitosan Membranes by Plasma Treatment
Authors: de Oliveira Cardoso Macêdo Marina , de Macêdo Haroldo Reis Alves , Gomes Dayanne Lopes , de Freitas Daudt Natália , Rocha Hugo Alexandre Oliveira , Alves Clodomiro
Published: November 2013

The use of polymeric medical devices has stimulated the development of new sterilization methods. The traditional techniques rely on ethylene oxide, but there are many questions concerning the carcinogenic properties of the ethylene oxide residues adsorbed on the materials after processing. Another common technique is the gamma irradiation process, but it is costly, its safe operation requires an isolated site, and it also affects the bulk properties of the polymers. The use of gas plasma is an elegant alternative sterilization technique. The plasma promotes efficient inactivation of the microorganisms, minimizes damage to the materials, and presents very little danger for personnel and the environment. In this study we used plasma for microbial inhibition of chitosan membranes. The membranes were treated with oxygen, methane, or argon plasma for different time periods (15, 30, 45, or 60 min). For inhibition of microbial growth with oxygen plasma, the time needed was 60 min. For the methane plasma, samples were successfully treated after 30, 45, and 60 min. For argon plasma, all treatment periods were effective.
Neuromuscular electrical stimulation prevents muscle disuse atrophy during leg immobilization in humans
Authors: Dirks M. L. , Wall B. T. , Snijders T. , Ottenbros C. L. P. , Verdijk L. B. , van Loon L. J. C.
Published: November 2013

Aim

Short periods of muscle disuse, due to illness or injury, result in substantial skeletal muscle atrophy. Recently, we have shown that a single session of neuromuscular electrical stimulation (NMES) increases muscle protein synthesis rates. The aim was to investigate the capacity for daily NMES to attenuate muscle atrophy during short‐term muscle disuse.

Methods

Twenty‐four healthy, young (23 ± 1 year) males participated in the present study. Volunteers were subjected to 5 days of one‐legged knee immobilization with (NMES; n = 12) or without (CON; n = 12) supervised NMES sessions (40‐min sessions, twice daily). Two days prior to and immediately after the immobilization period, CT scans and single‐leg one‐repetition maximum (1RM) strength tests were performed to assess quadriceps muscle cross‐sectional area (CSA) and leg muscle strength respectively. Furthermore, muscle biopsies were taken to assess muscle fibre CSA, satellite cell content and mRNA and protein expression of selected genes.

Results

In CON, immobilization reduced quadriceps CSA by 3.5 ± 0.5% (P < 0.0001) and muscle strength by 9 ± 2% (P < 0.05). In contrast, no significant muscle loss was detected following immobilization in NMES although strength declined by 7 ± 3% (P < 0.05). Muscle MAFbx and MuRF1 mRNA expression increased following immobilization in CON (P < 0.001 and P = 0.07 respectively), whereas levels either declined (P < 0.01) or did not change in NMES, respectively. Immobilization led to an increase in muscle myostatin mRNA expression in CON (P < 0.05), but remained unchanged in NMES.

Conclusion

During short‐term disuse, NMES represents an effective interventional strategy to prevent the loss of muscle mass, but it does not allow preservation of muscle strength. NMES during disuse may be of important clinical relevance in both health and disease.
The connection between children's knowledge and use of grapho‐phonic and morphemic units in written text and their learning at school
Authors: Bryant Peter , Nunes Terezinha , Barros Rossana
Published: November 2013

Background

Most psychologists who study children's reading assume that their hypotheses are relevant to children's success at school. This assumption is rarely tested.

Aims

The study's aims were to see whether two successful measures of the processes underlying children's learning to read and write are related to their success in English, science, and mathematics as measured by school assessments.

Sample

Data from the Avon Longitudinal Study of Parents and Children were available for between 2,500 and 5,900 children (in different analyses) on their use of graphophonic and morphemic units in reading and writing and on their achievement in Key Stage 2 and Key Stage 3 assessments.

Method

Hierarchical multiple regressions assessed the relationship between children's use of grapho‐phonic and morphemic units at 8‐ and 9‐years and their performance in the Key Stage 2 (11‐years) and Key Stage 3 (14‐years) assessments in English, mathematics, and science.

Results

The children's grapho‐phonic and morphemic skills predicted their achievement in all three subjects at Key Stage 2, 3 years later, and at Key Stage 3, 5 years later, even after stringent controls for differences in age and IQ. The connection between the two types of orthographic skills and the children's educational success was largely mediated by their reading ability as measured by standardised tests.

Conclusions

Children's knowledge and use of grapho‐phonic and morphemic rules has a lasting effect on the progress that they make at school. This knowledge has an impact on their reading ability which in turn affects their success in learning about English, mathematics and science.
EXPORT AND HEDGING DECISIONS UNDER CORRELATED REVENUE AND EXCHANGE RATE RISK
Authors: Wong Kit Pong
Published: November 2013

This paper examines the behaviour of a competitive exporting firm under joint revenue and exchange rate risk. The firm can trade unbiased currency futures contracts for hedging purposes. We show that neither the separation theorem nor the full‐hedging theorem holds when the revenue shock prevails. If the correlation between the revenue shock and the random spot exchange rate is non‐positive, the firm optimally produces less than the benchmark level when the revenue shock is absent. If, in addition, the firm is prudent, the optimal futures position is an under‐hedge. Finally, we derive sufficient conditions under which the firm's optimal output level is higher in the presence than in the absence of the revenue shock. Operational hedging and financial hedging as such interact in a complicated way to better cope with the multiple sources of uncertainty faced by the firm.
Structural requirements of steroidal agonists of transient receptor potential melastatin 3 (TRPM3) cation channels
Authors: Drews A , Mohr F , Rizun O , Wagner T F J , Dembla S , Rudolph S , Lambert S , Konrad M , Philipp S E , Behrendt M , Marchais‐Oberwinkler S , Covey D F , Oberwinkler J
Published: November 2013

Background and Purpose

Transient receptor potential melastatin 3 (TRPM3) proteins form non‐selective but calcium‐permeable membrane channels, rapidly activated by extracellular application of the steroid pregnenolone sulphate and the dihydropyridine nifedipine. Our aim was to characterize the steroid binding site by analysing the structural chemical requirements for TRPM3 activation.

Experimental Approach

Whole‐cell patch‐clamp recordings and measurements of intracellular calcium concentrations were performed on HEK293 cells transfected with TRPM3 (or untransfected controls) during superfusion with pharmacological substances.

Key Results

Pregnenolone sulphate and nifedipine activated TRPM3 channels supra‐additively over a wide concentration range. Other dihydropyridines inhibited TRPM3 channels. The natural enantiomer of pregnenolone sulphate was more efficient in activating TRPM3 channels than its synthetic mirror image. However, both enantiomers exerted very similar inhibitory effects on proton‐activated outwardly rectifying anion channels. Epiallopregnanolone sulphate activated TRPM3 almost equally as well as pregnenolone sulphate. Exchanging the sulphate for other chemical moieties showed that a negative charge at this position is required for activating TRPM3 channels.

Conclusions and Implications

Our data demonstrate that nifedipine and pregnenolone sulphate act at different binding sites when activating TRPM3. The latter activates TRPM3 by binding to a chiral and thus proteinaceous binding site, as inferred from the differential effects of the enantiomers. The double bond between position C5 and C6 of pregnenolone sulphate is not strictly necessary for the activation of TRPM3 channels, but a negative charge at position C3 of the steroid is highly important. These results provide a solid basis for understanding mechanistically the rapid chemical activation of TRPM3 channels.
Expression of CD39/Entpd1 on granuloma-composing cells and induction of Foxp3-positive regulatory T cells in sarcoidosis
Authors: Fujimura T. , Kambayashi Y. , Aiba S.
Published: November 2013

Background

Regulatory T cells (Tregs), together with tolerogenic dendritic cells (tDCs) are involved in maintaining peripheral tolerance. A recent report suggested both Tregs and tDCs may be pathogenic in granulomatous skin disorders.

Aim

To examined the expression of CD39 on granuloma-composing cells and Foxp3-positive Tregs in the skin in two representative granulomatous diseases, sarcoidosis and granuloma annulare (GA).

Methods

We immunohistologically examined expression of CD39 on granuloma-composing cells and expression of Foxp3 on CD4+ or CD25+ cells in fixed sections of lesional skin from 16 patients with sarcoidosis and five patients with GA.

Results

The granuloma-composing cells expressed CD39 in both sarcoidosis and GA. Significant numbers of CD4+ Foxp3+ Tregs were present diffusely throughout the granulomatous tissues in sarcoidosis, whereas Tregs in GA existed only at the peripheral lesion of palisading granulomatous tissue.

Conclusions

There was infiltration of increased numbers of Foxp3+ Tregs around the CD39+ granuloma-composing cells in both GA and sarcoidosis.
Evidence‐based genetic counselling implications for Huntington disease intermediate allele predictive test results
Authors: Semaka A. , Hayden M.R.
Published: November 2013

Intermediate alleles (IAs) for Huntington disease (HD) contain 27–35 CAG repeats, a range that falls just below the disease threshold of 36 repeats. While there is no firm evidence that IAs confer the HD phenotype, they are prone to germline CAG repeat instability, particularly repeat expansion when paternally transmitted. Consequently, offspring may inherit a new mutation and develop the disease later in life. Over the last 5 years there has been a renewed interest in IAs. This article provides an overview of the latest research on IAs, including their clinical implications, frequency, haplotype, and likelihood of CAG repeat expansion, as well as patient understanding and current genetic counselling practices. The implications of this growing evidence base for clinical practice are also highlighted. These evidence‐based genetic counselling implications may help ensure individuals with an IA predictive test result receive appropriate support, education, and counselling.
Pheromone release rate determines whether sexual communication of Oriental fruit moth is disrupted competitively vs. non‐competitively
Authors: Reinke M. D. , Siegert P. Y. , McGhee P. S. , Gut L. J. , Miller J. R.
Published: November 2013

Communicational disruption mechanisms for Oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae), were determined using a suite of mathematical tools and graphical operations that enable differentiation between competitive attraction and non‐competitive mechanisms of disruption. Research was conducted in 20 field cages, each covering 12 mature apple trees. Commercial monitoring lures releasing Oriental fruit moth pheromone at a rate of 0.04 μg h−1 and distributed at densities of 0, 1, 2, 4, 8, and 17 per cage were used to evaluate the effect of low‐releasing dispensers on the disruption of sexual communication. Graphical analyses revealed that near‐female‐equivalent pheromone dispensers disrupted Oriental fruit moth competitively. Commercial mating disruption dispensers releasing Oriental fruit moth pheromone at 60 μg h−1 and deployed at 0, 4, 6, 10, 15, 20, and 30 per cage were used to evaluate the effect of high‐releasing dispensers on the disruption of sexual communication. Oriental fruit moth disruption shifted to a non‐competitive mechanism for high‐releasing dispensers. This is the first time such a shift in disruption mechanism has been demonstrated against a background of otherwise identical experimental conditions. Near‐female‐equivalent pheromone dispensers were also used to quantify the additive effect of an attract‐and‐remove control strategy compared with competitive mating disruption. We report a five‐fold reduction in Oriental fruit moth captures under attract‐and‐remove compared to mating disruption using near‐female‐equivalent dispensers. Surprisingly, release of female Oriental fruit moths into these large‐cage disruption studies had no measurable impact on male trapping.
Nine key principles to guide youth mental health: development of service models in New South Wales
Authors: Howe Deborah , Batchelor Samantha , Coates Dominiek , Cashman Emma
Published: November 2013

Aims

Historically, the Australian health system has failed to meet the needs of young people with mental health problems and mental illness. In 2006, New South Wales (NSW) Health allocated considerable funds to the reform agenda of mental health services in NSW to address this inadequacy. Children and Young People's Mental Health (CYPMH), a service that provides mental health care for young people aged 12–24 years, with moderate to severe mental health problems, was chosen to establish a prototype Youth Mental Health (YMH) Service Model for NSW. This paper describes nine key principles developed by CYPMH to guide the development of YMH Service Models in NSW.

Methods

A literature review, numerous stakeholder consultations and consideration of clinical best practice were utilized to inform the development of the key principles.

Results

Subsequent to their development, the nine key principles were formally endorsed by the Mental Health Program Council to ensure consistency and monitor the progress of YMH services across NSW. As a result, between 2008 and 2012 YMH Services across NSW regularly reported on their activities against each of the nine key principles demonstrating how each principle was addressed within their service.

Conclusions

The nine key principles provide mental health services a framework for how to reorient services to accommodate YMH and provide a high‐quality model of care.

[Corrections added on 29 November 2013, after first online publication: The last two sentences of the Results section have been replaced with "As a result, between 2008 and 2012 YMH Services across NSW regularly reported on their activities against each of the nine key principles demonstrating how each principle was addressed within their service."]
Is the Problem Only Ours? A Question of Relevance in Management Research
Authors: Vicari Salvatore
Published: November 2013

Academics do not turn to managers for inspiration for their research and managers do not consult academics on theories to develop models and strategies. The resulting issue of the non‐relevance of research in this field is so controversial that it could limit the development of management studies. The problem, however, cannot be eliminated by simply calling for research on more relevant topics or hoping for greater collaboration between researchers and managers. The absence of a solution to this problem is not due to the unwillingness or lack of intelligence of researchers, but because science must be closed to external demands and therefore also to the managerial world. In this paper, I argue that the solution is not in opposing this closure, but incorporating it within a research and practice eco‐system that sets out from the fact that non‐relevance is not only a problem of the scientific community, but also of the managerial world: they have a problem too.
Does Spousal Support Moderate the Association Between Perceived Racial Discrimination and Depressive Symptoms among African American Couples?
Authors: McNeil Sharde’ N. , Fincham Frank D. , Beach Steven R. H.
Published: November 2013

Social stress theory proposes that stress resulting from one's social position in society leads to fewer coping resources, and subsequently causes an increase in mental health problems. Guided by this framework, we investigated whether the relationship between perceived discrimination and depressive symptoms was moderated by spousal social support in a sample of 487 African American heterosexual couples. Using the actor‐partner interdependence model, findings suggested that female partner's perceived racial discrimination was predictive of her depressive symptomology irrespective of spousal support and male partner's perceived racial discrimination was predictive of depressive symptomology only among men with low levels of spousal support. No partner effects were present. The results demonstrate the need to examine variability in social stress and mental health outcomes for those in close relationships.
Localization and behaviors in null mice suggest that ASIC1 and ASIC2 modulate responses to aversive stimuli
Authors: Price M. P. , Gong H. , Parsons M. G. , Kundert J. R. , Reznikov L. R. , Bernardinelli L. , Chaloner K. , Buchanan G. F. , Wemmie J. A. , Richerson G. B. , Cassell M. D. , Welsh M. J.
Published: November 2013

Acid‐sensing ion channels (ASICs) generate H+‐gated Na+ currents that contribute to neuronal function and animal behavior. Like ASIC1, ASIC2 subunits are expressed in the brain and multimerize with ASIC1 to influence acid‐evoked currents and facilitate ASIC1 localization to dendritic spines. To better understand how ASIC2 contributes to brain function, we localized the protein and tested the behavioral consequences of ASIC2 gene disruption. For comparison, we also localized ASIC1 and studied ASIC1−/− mice. ASIC2 was prominently expressed in areas of high synaptic density, and with a few exceptions, ASIC1 and ASIC2 localization exhibited substantial overlap. Loss of ASIC1 or ASIC2 decreased freezing behavior in contextual and auditory cue fear conditioning assays, in response to predator odor and in response to CO2 inhalation. In addition, loss of ASIC1 or ASIC2 increased activity in a forced swim assay. These data suggest that ASIC2, like ASIC1, plays a key role in determining the defensive response to aversive stimuli. They also raise the question of whether gene variations in both ASIC1 and ASIC2 might affect fear and panic in humans.
Post‐heading heat stress and yield impact in winter wheat of China
Authors: Liu Bing , Liu Leilei , Tian Liying , Cao Weixing , Zhu Yan , Asseng Senthold
Published: November 2013

Wheat is sensitive to high temperatures, but the spatial and temporal variability of high temperature and its impact on yield are often not known. An analysis of historical climate and yield data was undertaken to characterize the spatial and temporal variability of heat stress between heading and maturity and its impact on wheat grain yield in China. Several heat stress indices were developed to quantify heat intensity, frequency, and duration between heading and maturity based on measured maximum temperature records of the last 50 years from 166 stations in the main wheat‐growing region of China. Surprisingly, heat stress between heading and maturity was more severe in the generally cooler northern wheat‐growing regions than the generally warmer southern regions of China, because of the delayed time of heading with low temperatures during the earlier growing season and the exposure of the post‐heading phase into the warmer part of the year. Heat stress between heading and maturity has increased in the last decades in most of the main winter wheat production areas of China, but the rate was higher in the south than in the north. The correlation between measured grain yields and post‐heading heat stress and average temperature were statistically significant in the entire wheat‐producing region, and explained about 29% of the observed spatial and temporal yield variability. A heat stress index considering the duration and intensity of heat between heading and maturity was required to describe the correlation of heat stress and yield variability. Because heat stress is a major cause of yield loss and the number of heat events is projected to increase in the future, quantifying the future impact of heat stress on wheat production and developing appropriate adaptation and mitigation strategies are critical for developing food security policies in China and elsewhere.
Correlation between endogenous VWF:Ag and PK parameters and bleeding frequency in severe haemophilia A subjects during three‐times‐weekly prophylaxis with rFVIII‐FS
Authors: Lalezari S. , Martinowitz U. , Windyga J. , Enriquez M. M. , Delesen H. , Schwartz L. , Scharrer I.
Published: November 2013

Patients with severe haemophilia A experience frequent and spontaneous bleeding, causing debilitating damage to joints and decreasing quality of life. Prophylaxis with factor VIII (FVIII) reduces joint damage if initiated early. Circulating FVIII levels may be influenced by endogenous von Willebrand factor (VWF), a chaperone protein that binds and stabilizes FVIII. The aim of this study was to determine whether endogenous VWF antigen (VWF:Ag) levels are correlated with FVIII pharmacokinetic (PK) parameters and clinical outcomes in patients with severe haemophilia A. Previously treated, non‐inhibitor patients in a multinational, randomized, double‐blind, Ph II study received prophylaxis with once‐weekly BAY 79‐4980 (35 IU kg−1) or thrice‐weekly recombinant sucrose‐formulated FVIII (rFVIII‐FS; 25 IU kg−1). PK parameters were evaluated at weeks 1 and 26. The number of bleeds per patient during the study was captured as part of the core efficacy endpoint. Spearman rank correlations assessed relationships of VWF:Ag levels with patient age, PK and annualized bleeding rate. Of 131 study patients (aged 13−64 years; BAY 79‐4980, n = 63; rFVIII‐FS, n = 68), 27 (21%; n = 15 and 12 respectively) were evaluable for PK assessment. Baseline VWF:Ag levels correlated with patient age (P < 0.0001). There was no significant difference in PK results between treatments; thus, PK parameters and VWF levels of all patients were analysed together. AUCnorm and T1/2 significantly increased with increased VWF:Ag (P < 0.001); clearance significantly decreased with increased VWF:Ag (P = 0.002). Annualized bleeding rate in patients treated with 3× per week rFVIII‐FS significantly correlated with VWF:Ag and age (P = 0.038 and 0.021 respectively). PK parameters as well as the clinical outcome significantly correlated with endogenous VWF:Ag. The improved clinical outcome in subjects with high VWF:Ag levels may be explained by VWF:Ag influence on FVIII PK.
Effectiveness of two modalities of physiotherapy in the treatment of haemophilic arthropathy of the ankle: a randomized pilot study
Authors: Cuesta‐Barriuso R. , Gómez‐Conesa A. , López‐Pina J.‐A.
Published: November 2013

Although different techniques of physiotherapy have been described for the treatment of haemophilic arthropathy (HA) of ankle, hardly any studies have been applied manual therapy or educational physiotherapy and home exercises. The aim of this study was to assess the effectiveness of manual therapy and educational physiotherapy in the treatment of HA of the ankle. Thirty‐one patients with HA of the ankle with a mean age of 35.29 (SD: 12.877) years randomized to manual therapy group (n = 11), educational group (n = 10) and a control group (n = 10). The two physiotherapy programmes were one with manual therapy articular traction, passive stretching of the gastrocnemius muscles, and exercises for muscle strength and proprioception (MT group) and the other with educational sessions and home exercises (E group). The study lasted for 12 weeks. The treatment with manual therapy improved the gastrocnemius muscle circumference, and the pain of ankle (P < 0.05). Six months later, MT group still enjoyed improvement. In the educational group there were improvements, but not significant, in the measured variables. No patient had ankle haemarthrosis during the study. The treatment with manual therapy improved the circumference of gastrocnemius and lessened pain in the patients with haemophilic arthropathy of the ankle.
Expression of Mucin‐1 in multiple myeloma and its precursors: correlation with glycosylation and subcellular localization
Authors: Andrulis Mindaugas , Ellert Elena , Mandel Ulla , Clausen Henrik , Lehners Nicola , Raab Marc‐Steffen , Goldschmidt Hartmut , Schwartz‐Albiez Reinhard
Published: November 2013

Aims

Recent reports suggest a possible role for extracellular (MUC1N) and transmembrane (MUC1C) subunits of Mucin 1 (MUC1) in the pathogenesis of multiple myeloma (MM). Nuclear translocation of MUC1C is involved in activation of various oncogenic signalling pathways and both MUC1 subunits are potential therapeutic targets. We aimed at performing a comprehensive expression analysis of the MUC1 subunits in plasma cell dyscrasias.

Methods and results

Immunohistochemistry with monoclonal antibodies against the MUC1N subunit (EMA and 5E10) tumour‐associated glycoforms of MUC1N (5E5) and the MUC1C subunit were applied to a series of biopsies from normal controls (n = 10) and plasma cell dyscrasias (n = 121). Clonal plasma cells showed reduced MUC1N expression, and the 5E5 MUC1N epitope was expressed only in neoplastic plasma cells. Nuclear localization of MUC1C was equally frequent in all disease stages and did not differ from the control cases. Loss of both MUC1 subunits in MM (n = 12) was associated with significantly shorter overall survival and was more frequent in pretreated MM samples.

Conclusions

Our findings indicate that aberrant glycosylation of MUC1 is an early event in the pathogenesis of MM. In contrast, MUC1C nuclear localization is not likely to be a driver of tumour progression.
National sovereignty and transnational labour: the case of Mexican seasonal agricultural workers in British Columbia, Canada
Authors: Vosko Leah F.
Published: November 2013

This article analyses the experience of recently unionised Mexican seasonal agricultural workers in British Columbia, Canada, whose visa reapplications were blocked by Mexico and a concomitant complaint to the province's labour board. Illustrating the significance of this sending state's actions, it reveals the growing disjuncture between nationally based labour relations systems and transnational labour.
Employment relations on major construction projects: the London 2012 Olympic construction site
Authors: Druker Janet , White Geoffrey
Published: November 2013

The construction of the London 2012 Olympic Park provided a model of employee relations that crossed organisational boundaries. This model was countercultural, contrasting with the unregulated approaches that are commonplace in construction and contrasting too with collaborative models that have been developed on other major projects.
Science supporting negative pressure wound therapy with instillation
Authors: Rycerz Anthony M , Allen Diwi , Lessing M Christian
Published: November 2013

A new method (V.A.C.ULTA™ Therapy System, KCI USA, Inc., San Antonio, TX) combines the benefits of negative pressure wound therapy (NPWT; V.A.C.® Therapy, KCI USA, Inc.) with regulated, periodic instillation of user‐selected topical wound solutions (V.A.C. VeraFlo™ Therapy, KCI USA, Inc.). In simulated wound model studies comparing solution distribution using NPWT with and without a soak phase, the instillation soak phase allowed for uniform solution distribution across the wound bed, whereas continuous (no soak) irrigation resulted in uneven coverage. Additional in vitro work illustrated that bacterial particle aerosolisation during wound cleansing was significantly decreased using NPWT with instillation (NPWTi) versus commercially available low‐pressure wound cleansers (P < 0·05). In porcine studies, NPWT with saline instillation induced 43% more granulation tissue versus NPWT (P < 0·05) and was as effective at wound cleansing as pulsed lavage. These studies have demonstrated that NPWTi may be an effective wound management therapy that provides both wound cleansing and NPWT benefits.
Antimicrobial and antiseptic strategies in wound management
Authors: Daeschlein Georg
Published: November 2013

Wounds, especially chronic wounds, represent a global problem costing millions of dollars per year in developed countries and are characterised by microbial complications including local or overt infection, delayed healing and spread of multiresistant germs. Therefore, antimicrobial wound management is a major challenge that continues to require new solutions against microbes and their biofilms. As systemic antibiotics can barely penetrate into wound biofilms and topically applied ones can easily lead to sensitisation, antisepsis is the method of choice to treat germs in wounds. This brief review discusses the role of antiseptics in reducing bioburden in chronic wounds. Balancing antimicrobial potency and tolerability of antiseptic procedures is critical in wound therapy. However, antiseptics alone may not be able to achieve wound healing without addressing other factors regarding the patient's general health or the wound's physical environment. Although the precise role of bioburden in chronic wounds remains to be evaluated, planktonic as well as biofilm‐bound microbes are indications for antiseptic intervention. Octenidine dihydrochloride and polyhexanide are the most effective, as well as best tolerated, antiseptics in wound management today, and new strategies to reduce bacterial wound burden and support the body's immune response are being developed.
Activation of granulocytes by anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis: a predominant role for the IgG3 subclass of ANCA
Authors: MULDER A H L , STEGEMAN C A , KALLENBERG C G M
Published: November 2013

To study ANCA-induced granulocyte activation in relation to disease activity in Wegener's granulomatosis (WG), serum samples taken from patients with WG at the time of active (n = 17) and inactive (n = 17) disease were analysed for their capacity to activate primed normal donor granulocytes. Compared with control sera (n = 6), the capacity of IgG fractions from patients with WG to induce the respiratory burst was significantly higher (P < 0·0001). Furthermore, the capacity to induce the respiratory burst significantly correlated with ANCA titre (r = 0·499, P = 0·003). IgG fractions from patients with active extensive disease induced the respiratory burst significantly more stongly than IgG fractions from patients with limited disease (n = 7) (P < 0·01) or patients during disease remission (n = 17) (P < 0·001). As ANCA-induced neutrophil activation is Fc-dependent and different IgG subclasses are involved in the interaction with various Fc receptors from neutrophils, we assessed changes in ANCA titre, total IgG and IgG subclass distribution of ANCA during active disease and remission in relation to the neutrophil-activating capacity of ANCA. Changes in capacity to activate granulocytes were related neither to changes in titre nor to changes in levels of total IgG, IgG1, IgG3, or IgG4 subclass of ANCA. However, changes in capacity to induce the respiratory burst were significantly related to changes in the relative amount of the IgG3 subclass of ANCA (P < 0·001), and not to changes in the relative amount of IgG1 or IgG4 subclass of ANCA. These data suggest that the increase in neutrophil-activating capacity of ANCA from inactive to active disease is, at least in part, based on the relative increase of the IgG3 subclass of ANCA that occurs during active disease.