bluuebunny/crossref_metadata_2025 huggingface dataset:
Oil‐in‐Water Emulsion Exhibits Bitterness‐Suppressing Effects in a Sensory Threshold Study
Authors: Torrico Damir Dennis , Sae‐Eaw Amporn , Sriwattana Sujinda , Boeneke Charles , Prinyawiwatkul Witoon
Published: May 2015

Little is known about how emulsion characteristics affect saltiness/bitterness perception. Sensory detection and recognition thresholds of NaCl, caffeine, and KCl in aqueous solution compared with oil‐in‐water emulsion systems were evaluated. For emulsions, NaCl, KCl, or caffeine were dissolved in water + emulsifier and mixed with canola oil (20% by weight). Two emulsions were prepared: emulsion 1 (viscosity = 257 cP) and emulsion 2 (viscosity = 59 cP). The forced‐choice ascending concentration series method of limits (ASTM E‐679‐04) was used to determine detection and/or recognition thresholds at 25 °C. Group best estimate threshold (GBET) geometric means were expressed as g/100 mL. Comparing NaCl with KCl, there were no significant differences in detection GBET values for all systems (0.0197 ‐ 0.0354). For saltiness recognition thresholds, KCl GBET values were higher compared with NaCl GBET (0.0822 ‐ 0.1070 compared with 0.0471 ‐ 0.0501). For NaCl and KCl, emulsion 1 and/or emulsion 2 did not significantly affect the saltiness recognition threshold compared with that of the aqueous solution. However, the bitterness recognition thresholds of caffeine and KCl in solution were significantly lower than in the emulsions (0.0242 ‐ 0.0586 compared with 0.0754 ‐ 0.1025). Gender generally had a marginal effect on threshold values. This study showed that, compared with the aqueous solutions, emulsions did not significantly affect the saltiness recognition threshold of NaCl and KCl, but exhibited bitterness‐suppressing effects on KCl and/or caffeine.
Discovery and characterization of single nucleotide polymorphisms in coho salmon, Oncorhynchus kisutch
Authors: Starks Hilary A. , Clemento Anthony J. , Garza John Carlos
Published: May 2015

Molecular population genetic analyses have become an integral part of ecological investigation and population monitoring for conservation and management. Microsatellites have been the molecular marker of choice for such applications over the last several decades, but single nucleotide polymorphism (SNP) markers are rapidly expanding beyond model organisms. Coho salmon (Oncorhynchus kisutch) is native to the north Pacific Ocean and its tributaries, where it is the focus of intensive fishery and conservation activities. As it is an anadromous species, coho salmon typically migrate across multiple jurisdictional boundaries, complicating management and requiring shared data collection methods. Here, we describe the discovery and validation of a suite of novel SNPs and associated genotyping assays which can be used in the genetic analyses of this species. These assays include 91 that are polymorphic in the species and one that discriminates it from a sister species, Chinook salmon. We demonstrate the utility of these SNPs for population assignment and phylogeographic analyses, and map them against the draft trout genome. The markers constitute a large majority of all SNP markers described for coho salmon and will enable both population‐ and pedigree‐based analyses across the southern part of the species native range.
Herbivory and fire interact to affect forest understory habitat, but not its use by small vertebrates
Authors: Foster C. N. , Barton P. S. , Sato C. F. , Wood J. T. , MacGregor C. I. , Lindenmayer D. B.
Published: May 2015

Herbivory and fire are two disturbances that often co‐occur, but studies of their interactive effects are rare outside of grassland ecosystems. We experimentally tested the interactive effects of prescribed fire and macropod herbivory on forest understory vegetation and its vertebrate fauna. Fire and herbivory interacted synergistically to affect forest understory vegetation, with palatable plants showing poor post‐fire recovery in unfenced sites compared with herbivore exclusion sites. Despite this strong interactive effect on vegetation, small vertebrates responded to the individual, and not the interactive effects of disturbance. The native insectivorous mammal Antechinus stuartii was more frequently encountered on large herbivore exclusion sites, as was the introduced European rabbit. In contrast, the small skink Lampropholis delicata was more common on sites with high densities of large herbivores. Skinks, snakes and European rabbits were also more active on burnt than unburnt sites. Our results suggest that it may be necessary to manage the macropod herbivore population after fire to prevent the decline of palatable plants, and maintain the dense habitat required by some small mammals. However, as the invasive rabbit was most active in macropod‐free sites after fire, any management must include control of both types of herbivores. A mix of understory densities may also need to be maintained to ensure the persistence of species preferring more open habitats. Our study demonstrates that interactive effects of disturbance on vegetation communities may not lead to predictable effects on animals, and highlights the importance of considering both multiple stressors, and multiple species, in the management of disturbance regimes.
Transition probabilities for four states of alcohol use in adolescence and young adulthood: what factors matter when?
Authors: Probst Charlotte , Moyo Daniel , Purshouse Robin , Rehm Jürgen
Published: May 2015

Background and Aims

Risky single‐occasion drinking (RSOD) is a health threat, particularly at younger ages. The study aimed to quantify transition probabilities (TPs) between abstinence, use of alcohol, RSOD and frequent RSOD, and to understand how TPs are associated with key demographic factors.

Design

Cohort study (baseline, two follow‐ups). A Markov model was fitted to estimate annual TPs and hazard ratios (HRs) for age, sex and socio‐economic status (SES).

Setting

Adolescent and young adult general population of Munich (Germany) and surrounding areas.

Participants

A total of 3021 people aged 14–25 years at baseline in 1995 followed‐up in 1998/1999 (n = 2548) and 2003–2005 (n = 2210).

Measurements

Alcohol use, RSOD status, age, sex and SES (subjective financial situation) were assessed in a standardized interview.

Findings

The highest TPs (> 65%) were found for staying in the same drinking state. Higher age [hazard ratio (HR) for 1‐year increase = 0.87, 95% confidence interval (CI) = 0.84–0.91], being female (HR = 0.30, 95% CI = 0.21–0.42), and a high SES (HR = 0.64, 95% CI = 0.43–0.97) were associated with a lower hazard to progress from use to RSOD. While age was associated predominantly with transitions between abstinence and alcohol use, sex was more relevant for transitions associated with RSOD and frequent RSOD.

Conclusions

German adolescents and young adults tend to be stable in the drinking states of abstinence, use of alcohol, risky single‐occasion drinking and frequent risky single‐occasion drinking. Females are less likely to transition to riskier states and more likely to transition back from frequent risky single‐occasion drinking, higher age is associated with lower hazard of transitioning and participants of higher socio‐economic status are less likely to transition from ‘use of alcohol’ to ‘risky single‐occasion drinking’.
Outcomes of placing short implants in the posterior mandible: a preliminary randomized controlled trial
Authors: Al‐Hashedi AA , Taiyeb‐Ali TB , Yunus N
Published: May 2015

Background

Short dental implants can be an alternative to bone augmentation procedures at sites of reduced alveolar bone. Most studies on short implants are retrospective or multicentre reports that lack controlled and consistent comparison between different systems. This study aimed to compare clinical and radiographic outcomes of short implants in two different systems in the posterior mandible.

Methods

Twenty patients with two adjacent missing posterior teeth were recruited. Patients were assigned equally and randomly into two groups; Bicon® (6 or 8 mm) and Ankylos® (8 mm) implants. A two‐stage surgical approach and single crowns were used for implant placement and loading. Outcomes included peri‐implant clinical parameters, implant stability (Periotest values; PTVs) and peri‐implant bone changes, which were assessed at baseline, 2, 6 and 12 months post‐loading.

Results

No implant loss was encountered up to 12 months post‐loading. No significant difference in the clinical or radiographic parameters was observed except for PTVs (p < 0.05) that was lower in Ankylos® implants.

Conclusions

The use of short dental implants was associated with excellent 12 months clinical and radiographic outcomes. Ankylos® and Bicon® implants demonstrated similar peri‐implant soft tissue and alveolar bone changes. However, Ankylos® implants demonstrated better implant stability at all evaluation intervals.
Implementation and evaluation of a checklist to improve patient care on surgical ward rounds
Authors: Pitcher Meron , Lin Joshua T. W. , Thompson Graeme , Tayaran Ammar , Chan Steven
Published: May 2015

Background

Key aspects of care may be overlooked on a busy surgical ward round. This study assessed the use of a checklist to correct these omissions. Its use as the basis of structured ward round documentation was then measured.

Methods

Using a structured checklist, key aspects of surgical care were observed and recorded during ward rounds. Initially, members of the surgical team were unaware of the checklist. Subsequently, rounds were performed with a designated member of the team acting as ‘prompter’ if aspects of care were not considered per the checklist. A structured ward round progress form was developed and its completion assessed before and after specific education in its use. Changes in the use of checklist and documentation using the structured form were analysed for statistical significance.

Results

Following the use of a checklist and prompting during ward rounds, significant improvement occurred in the consideration of the majority of criteria included in the checklist, all of which reached statistical significance (P < 0.05). Provision of a structured progress form did not initially improve documentation but this was substantially improved with specific education (P < 0.05).

Conclusion

The use of a checklist during surgical ward rounds makes significant improvement in the consideration of most key aspects of care and education in the completion of a structured progress form substantially improved documentation.
COFFEE CO‐OPERATIVES IN MALAWI: BUILDING RESILIENCE THROUGH INNOVATION
Authors: BORDA‐RODRIGUEZ Alexander , VICARI Sara
Published: May 2015

This article focuses on the role played by innovation in the context of coffee co‐operatives. It shows how interconnected forms of innovation contribute to co‐operative resilience. Data was collected from the largest coffee co‐operative Union in Malawi and illustrates how coffee co‐operatives have innovated in order to cope with organizational and market constrains. We identify four areas of innovation: sustainable technologies, development of market niches, women's inclusion and business diversification. The combination of these forms of innovation contributes to co‐operative resilience in different degrees, the article also analyzes how innovation is influenced and driven by co‐operative's values and principles and by partnerships with national and international actors.
INCENTIVES, PROCUREMENT AND REGULATION OF WORK INTEGRATION SOCIAL ENTERPRISES IN FRANCE: OLD IDEAS FOR NEW FIRMS?
Authors: GIANFALDONI Patrick , MORAND Pierre‐Henri
Published: May 2015

Work Integration Social Enterprises (WISEs) in France become increasingly dependent on commercial resources through public and private markets. Following New Public Management reforms that try to modernize the sector via market oriented management, they have restructured and modified their practices. We compare the normative prescriptions of the theory of incentives in regulation to the actual practices. The trend toward competitive process is described and the form of incentives contract toward workfare is detailed. Are the main insights of this literature appealing for this kind of enterprises? Do the traditional incentives and contract theories ignore some very specific features of WISEs entities? We point out the drawbacks of potentially inaccurate forms of regulation contracts currently used.
Smoking prevalence and its influence on disease course and surgery in Crohn's disease and ulcerative colitis
Authors: Lunney P. C. , Kariyawasam V. C. , Wang R. R. , Middleton K. L. , Huang T. , Selinger C. P. , Andrews J. M. , Katelaris P. H. , Leong R. W. L.
Published: May 2015

Background

Smoking demonstrates divergent effects in Crohn's disease (CD) and ulcerative colitis (UC). Smoking frequency is greater in CD and deleterious to its disease course. Conversely, UC is primarily a disease of nonsmokers and ex‐smokers, with reports of disease amelioration in active smoking.

Aim

To determine the prevalence of smoking and its effects on disease progression and surgery in a well‐characterised cohort of inflammatory bowel diseases (IBD) patients.

Methods

Patients with smoking data of the Sydney IBD Cohort were included. Demographic, phenotypic, medical, surgical and hospitalisation data were analysed and reported on the basis of patient smoking status.

Results

1203 IBD patients were identified comprising 626 CD and 557 UC with 6725 and 6672 patient‐years of follow‐up, respectively. CD patients were more likely to smoke than UC patients (19.2% vs. 10.2%, P < 0.001). A history of smoking in CD was associated with an increased proportional surgery rate (45.8% vs. 37.8%, P = 0.045), requirement for IBD‐related hospitalisation (P = 0.009) and incidence of peripheral arthritis (29.8% vs. 22.0%, P = 0.027). Current smokers with UC demonstrated reduced corticosteroid utilisation (24.1% vs. 37.5%, P = 0.045), yet no reduction in the rates of colectomy (3.4% vs. 6.6%, P = 0.34) or hospital admission (P = 0.25) relative to nonsmokers. Ex‐smokers with UC required proportionately greater immunosuppressive (36.2% vs. 26.3%, P = 0.041) and corticosteroid (43.7% vs. 34.5%, P = 0.078) therapies compared with current and never smokers.

Conclusions

This study confirms the detrimental effects of smoking in CD, yet failed to demonstrate substantial benefit from smoking in UC. These data should encourage all patients with IBD to quit smoking.
Liberalism and Public Health Ethics
Authors: Rajczi Alex
Published: May 2015

Many public health dilemmas involve a tension between the promotion of health and the rights of individuals. This article suggests that we should resolve the tension using our familiar liberal principles of government. The article considers the common objections that (i) liberalism is incompatible with standard public health interventions such as anti‐smoking measures or intervention in food markets; (2) there are special reasons for hard paternalism in public health; and (3) liberalism is incompatible with proper protection of the community good. The article argues that we should examine these critiques in a larger methodological framework by first acknowledging that the right theory of public health ethics is the one we arrive at in reflective equilibrium. Once we examine the arguments for and against liberalism in that light, we can see the weaknesses in the objections and the strength of the case for liberalism in public health.
Does forming implementation intentions help people with mental health problems to achieve goals? A meta‐analysis of experimental studies with clinical and analogue samples
Authors: Toli Agoro , Webb Thomas L. , Hardy Gillian E.
Published: May 2015

Objective

People struggle to act on the goals that they set themselves, and this gap between intention and action is likely to be exacerbated by mental health problems. Evidence suggests that forming specific if‐then plans (or ‘implementation intentions’) can promote goal attainment and a number of studies have applied such techniques in clinical contexts. However, to date, the extent to which planning can help people with mental health problems has not been systematically examined.

Method

The present review used meta‐analysis to investigate the effect of if‐then planning on goal attainment among people with a DSM‐IV/ICD‐10 diagnosis (i.e., clinical samples) or scores above a relevant cut‐off on clinical measures (i.e., analogue samples). In total, 29 experimental studies, from 18 records, met the inclusion criteria.

Results

Excluding one outlying (very large) effect, forming implementation intentions had a large‐sized effect on goal attainment (d+ = 0.99, k = 28, N = 1,636). Implementation intentions proved effective across different mental health problems and goals, and in studies with different methodological approaches.

Conclusions

Taken together, the findings suggest that forming implementation intentions can be a useful strategy for helping people with mental health problems to achieve various goals and might be usefully integrated into existing treatment approaches. However, further studies are needed addressing a wider range of mental health problems.

Practitioner points

This meta‐analysis suggests that prompting people with mental health problems to form if‐then plans (known as ‘implementation intentions’) specifying when, where, and how they will achieve their goals can be beneficial.

The findings proved robust across a range of methodologies, samples, and focal goals, suggesting that forming implementation intentions can help people with a range of mental health problems to achieve a range of different goals.

We provide guidance to researchers and practitioners in how to promote the formation of implementation intentions.
Population‐based study of long‐term functional outcomes after prostate cancer treatment
Authors: Carlsson Sigrid , Drevin Linda , Loeb Stacy , Widmark Anders , Lissbrant Ingela Franck , Robinson David , Johansson Eva , Stattin Pär , Fransson Per
Published: May 2015

Objective

To evaluate long‐term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median (interquartile range) follow‐up of 12 (11–13) years.

Patients and Methods

In this nationwide, population‐based study, we identified 6 003 men diagnosed with localized prostate cancer (clinical local stage T1–2, any Gleason score, prostate‐specific antigen <20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 from the National Prostate Cancer Register, Sweden. The men were aged ≤70 years at diagnosis. A control group of 1 000 men without prostate cancer were also selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self‐reported questionnaire.

Results

Responses were obtained from 3 937/6 003 cases (66%) and 459/1 000 (46%) controls. At 12 years after diagnosis and at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction/sexual inactivity, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62, 6 and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction compared with the men in the control group. Radical prostatectomy was associated with an increased risk of urinary incontinence (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.36–2.62) and radiotherapy increased the risk of bowel dysfunction (OR 2.46, 95% CI 1.73–3.49) compared with men in the control group. Multi‐modal treatment, in particular treatment including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance, radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 (95% CI 1.76–7.95) for erectile dysfunction and an OR of 3.22 (95% CI 1.93–5.37) for urinary incontinence.

Conclusion

The proportion of men who experienced a long‐term impact on functional outcomes after prostate cancer treatment was substantial.
Radical Innovation with Limited Resources in High‐Turbulent Markets: The Role of Lean Innovation Capability
Authors: Bicen Pelin , Johnson William H.A.
Published: May 2015

How do firms radically innovate with limited resources in high‐turbulent environments? We examine this question via in‐depth comparative case studies of ten start‐up firms in diverse high‐turbulent markets. Evidence shows that the perceived value of resources depends on two contextual factors: market type and business model type. More interestingly, firms that see resource limitation as an enabler rather than an inhibitor seem to have a distinct capability that we call lean innovation capability. It is defined as a distinct capability that reflects a firm's ability to experiment with ideas that meet core customer needs by constantly iterating the initial offering with the purpose of validating the learning through continuous market feedback to achieve sustainable performance. The three main qualities of these companies are (1) adopting abductive reasoning, (2) embracing a validity‐driven approach, and (3) operating in the overlapping spaces of fundamental customer needs, business viability and technological feasibility. Lean firms adopt design‐thinking methodology and act like bricoleurs, such as make‐do by applying combinations of the available resources through rapid prototyping to new problems and opportunities in an experimental way. Briefly, lean innovation capability enables firms to manage limited resources by reconfiguring and reallocating existing resources, and, thereby, helps empower resource‐limited radical innovation.
The Ludic Drive as Innovation Driver: Introduction to the Gamification of Innovation
Authors: Roth Steffen , Schneckenberg Dirk , Tsai Chia‐Wen
Published: May 2015

Gamification has recently been receiving increased attention in corporate innovation and business research alike. In this article, we first outline the main streams of research on gamification in the creativity and innovation literature. We then introduce the selection of contributions to this special section by theoretically embedding them in their application contexts. Thus referring to research fields as different as business model innovation, design thinking and crowdsourcing, we indicate theoretical challenges for future research on gamification, among the most important of which we count theoretical approaches to the question of whether and how organizations actually can play with persons.
Heat‐Shock Protein 90 (Hsp90) as Anticancer Target for Drug Discovery: An Ample Computational Perspective
Authors: Kumalo Hezekiel M. , Bhakat Soumendranath , Soliman Mahmoud E.
Published: May 2015

There are over 100 different types of cancer, and each is classified based on the type of cell that is initially affected. If left untreated, cancer can result in serious health problems and eventually death. Recently, the paradigm of cancer chemotherapy has evolved to use a combination approach, which involves the use of multiple drugs each of which targets an individual protein. Inhibition of heat‐shock protein 90 (Hsp90) is one of the novel key cancer targets. Because of its ability to target several signaling pathways, Hsp90 inhibition emerged as a useful strategy to treat a wide variety of cancers. Molecular modeling approaches and methodologies have become ‘close counterparts’ to experiments in drug design and discovery workflows. A wide range of molecular modeling approaches have been developed, each of which has different objectives and outcomes. In this review, we provide an up‐to‐date systematic overview on the different computational models implemented toward the design of Hsp90 inhibitors as anticancer agents. Although this is the main emphasis of this review, different topics such as background and current statistics of cancer, different anticancer targets including Hsp90, and the structure and function of Hsp90 from an experimental perspective, for example, X‐ray and NMR, are also addressed in this report. To the best of our knowledge, this review is the first account, which comprehensively outlines various molecular modeling efforts directed toward identification of anticancer drugs targeting Hsp90. We believe that the information, methods, and perspectives highlighted in this report would assist researchers in the discovery of potential anticancer agents.
Vitamins A and D have antagonistic effects on expression of effector cytokines and gut‐homing integrin in human innate lymphoid cells
Authors: Ruiter B. , Patil S. U. , Shreffler W. G.
Published: May 2015

Background

Retinoic acid (RA), the main biologically active metabolite of vitamin A, is known to promote gut homing of lymphocytes, as well as various regulatory and effector immune responses. In contrast, the active form of vitamin D, 1,25‐dihydroxyvitamin D3 (1,25D3), is predominantly immunosuppressive. Little is known about the direct effects of these vitamins on the recently identified innate lymphoid cells (ILCs).

Objective

We sought to characterize the effects of RA and 1,25D3 on human ILCs.

Methods

Peripheral blood mononuclear cells were isolated from 27 non‐selected blood donor buffy coats, and ILCs were sorted by FACS. ILC1, ILC2, and ILC3 cells were cultured for 5 days with RA, 1,25D3, and various cytokines known to activate ILCs (IL‐2, IL‐7, IL‐12, thymic stromal lymphopoietin (TSLP), IL‐25, and IL‐33). Cytokines produced by ILCs were measured in culture supernatants, and surface receptor expression was analysed by flow cytometry.

Results

Retinoic acid acted synergistically with IL‐2 and other activating cytokines to induce expression of the gut‐homing integrin α4β7 in ILCs, as well as production of IL‐5 and IL‐13 in ILC2 cells, and IFN‐γ in ILC1 and ILC3 cells. Expression of integrin α4β7 and cytokine production in ILCs stimulated with RA + IL‐2 was increased at least fourfold as compared to ILCs cultured with RA or IL‐2 alone. In contrast, RA completely inhibited the IL‐2‐induced expression of cutaneous lymphocyte antigen (CLA) in ILCs. Moreover, addition of 1,25D3 to ILCs cultured with RA + IL‐2 inhibited cytokine production and expression of integrin α4β7 by at least 30%.

Conclusions

Retinoic acid and 1,25D3 have antagonistic effects on the expression of effector cytokines and gut‐homing integrin by human ILCs. The balance between these vitamins may be an important factor in the functioning of ILCs and the diseases in which ILCs are implicated, such as allergic inflammation.
Clinical presentation of hyperthyroidism in a large representative sample of outpatients in France: relationships with age, aetiology and hormonal parameters
Authors: Goichot B. , Caron Ph. , Landron F. , Bouée S
Published: May 2015

Objective

Signs and symptoms of thyrotoxicosis are not specific, and thyroid function tests are frequently prescribed to recognize such thyroid dysfunction. Ultrasensitive assays of thyroid‐stimulating hormone (TSH) allow early diagnosis and identification of mild hyperthyroidism (generally designed as ‘subclinical’). The aim of this study was to re‐evaluate the clinical picture of thyrotoxicosis in the context of the current large utilization of ultrasensitive TSH assays.

Design

Prospective descriptive cohort.

Methods

Clinical presentation of 1572 patients with a recent (<3 months) diagnosis of thyrotoxicosis recruited by a large representative sample of 263 French endocrinologists was studied using two questionnaires (one at inclusion and the second after 3 months) concerning symptoms, hormonal evaluation and treatment.

Results

A total of 1240 (78·9%) patients were women, mean age 48 ± 17 years. Subclinical hyperthyroidism (SCHT) was present in 86 patients (10·4%). Symptoms of thyrotoxicosis were in decreasing frequency order: palpitations, weakness, heat‐related signs and disturbed sleep. A total of 64·9% of patients had lost weight. Signs and symptoms were more frequent in Graves' disease, in young patients, and were partially related to biochemical severity. Symptoms were less frequent in elderly patients except for cardiac manifestations (atrial fibrillation). Most patients with SCHT had one or several signs or symptoms of thyrotoxicosis.

Conclusion

This study confirms that elderly patients have less symptoms of thyrotoxicosis than younger subjects but are at increased risk of cardiac complications. Our results show that most patients with ‘subclinical’ HT have in fact signs or symptoms of thyrotoxicosis.
Mutations in RIT1 cause Noonan syndrome – additional functional evidence and expanding the clinical phenotype
Authors: Koenighofer M. , Hung C. Y. , McCauley J. L. , Dallman J. , Back E. J. , Mihalek I. , Gripp K. W. , Sol‐Church K. , Rusconi P. , Zhang Z. , Shi G‐X. , Andres D. A. , Bodamer O. A.
Published: May 2015

RASopathies are a clinically heterogeneous group of conditions caused by mutations in 1 of 16 proteins in the RAS‐mitogen activated protein kinase (RAS‐MAPK) pathway. Recently, mutations in RIT1 were identified as a novel cause for Noonan syndrome. Here we provide additional functional evidence for a causal role of RIT1 mutations and expand the associated phenotypic spectrum. We identified two de novo missense variants p.Met90Ile and p.Ala57Gly. Both variants resulted in increased MEK‐ERK signaling compared to wild‐type, underscoring gain‐of‐function as the primary functional mechanism. Introduction of p.Met90Ile and p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human phenotype but also revealed abnormalities of eye development, emphasizing the importance of RIT1 for spatial and temporal organization of the growing organism. In addition, we observed severe lymphedema of the lower extremity and genitalia in one patient. We provide additional evidence for a causal relationship between pathogenic mutations in RIT1, increased RAS‐MAPK/MEK‐ERK signaling and the clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity or a diminished ability to interact with cellular GTPase activating proteins; however the precise mechanism remains unknown. The phenotypic spectrum is likely to expand and includes lymphedema of the lower extremities in addition to nuchal hygroma.
Revisiting tetranitrophenolsulfonephthalein
Authors: Mchedlov‐Petrossyan Nikolay O. , Roshchyna Kateryna V. , Shekhovtsov Sergey V. , Eltsov Sergey V. , Zozulia Oleksii S. , Omelchenko Irina V. , Shishkin Oleg V.
Published: May 2015

Among the vast series of phenolsulfonephthalein dyes, the nitro derivatives and especially 3,3′,5,5′‐tetranitrophenolsulfonephthalein (nitrophenol crimson) remain practically unexplored, whereas the halogen and alkyl derivatives have been studied comprehensively. This striking difference is probably due to the enormous influence of the four NO2 groups on the properties of the dye. As a result, the protolytic behaviour is unlike even that of tetrabromo phenolsulfonephthalein, and the recognised scheme of acid–base and tautomeric equilibrium of the sulfonephthaleins is unable to explain it. The molecular form H2R was isolated as a sultonic tautomer, and an X‐ray crystal structure analysis was carried out. Our studies of the UV‐vis absorption spectra in water, methanol, dimethyl sulfoxide, acetonitrile, acetone, and dichloromethane, as well as in aqueous micellar solutions of surfactants, allowed us to evaluate the true molar absorptivity of the dianion R2−, and to elucidate the enormous tendency to form yellow trianionic carbinol ROH3−, even in the presence of traces of H2O. Nuclear magnetic resonance and electrospray data confirm the proposed scheme of ionisation and tautomerism of nitrophenol crimson.
Deep‐coloured polyester/cotton blends with low concentrations of polymethylol dyes by a one‐pass continuous dyeing process
Authors: Zhao Hongjuan , Zhang Shufen
Published: May 2015

An obvious limitation of the one‐pass continuous dyeing process for polyester/cotton blends is its inability to achieve deep colour depth, which is caused by the low dye fixation yields of commercial reactive dyes. In this study, the performances of polyester/cotton blends dyed with high‐fixation polymethylol dyes and disperse dyes were compared with those of polyester/cotton blends dyed with a mixture of reactive dyes and disperse dyes. Polymethylol dyes were observed to be suitable for dyeing polyester/cotton blends when used in low concentrations; the required concentrations of polymethylol dyes were only 23–58% of the concentrations of commercial reactive dyes required to reach a given colour level on polyester/cotton blends. The wash and crocking fastness of polyester/cotton blends dyed with polymethylol dyes were similar to those of polyester/cotton blends dyed with reactive dyes.
Bounded Entrepreneurial Vitality: The Mixed Embeddedness of Female Entrepreneurship
Authors: Langevang Thilde , Gough Katherine V. , Yankson Paul W. K. , Owusu George , Osei Robert
Published: May 2015

Despite the recent increased interest in female entrepreneurs, attention has tended to focus on dynamic individuals and generic incentives without considering the roles of gender and place in entrepreneurship. In this article, we draw on the notion of mixed embeddedness to explore how time‐and‐place–specific institutional contexts influence women's entrepreneurship. Drawing on primary data collected in Ghana, where exceptionally more women engage in entrepreneurial activities than men, we examine the scale and characteristics of female entrepreneurial activity, exploring the factors that account for this strong participation of women, and examine whether this high entrepreneurial rate is also reflected in their performance and growth aspirations. The findings reveal a disjuncture between, on the one hand, the vibrant entrepreneurial endeavors of Ghanaian women and positive societal attitudes toward female entrepreneurship and, on the other hand, female business activities characterized by vulnerability and relatively low achievement. The article shows how regulatory, normative, and cultural–cognitive institutional forces, which have been transformed over time by local and global processes and their interaction, are concomitantly propelling and impeding women's entrepreneurial activities. We propose that the study of female entrepreneurs within economic geography could be advanced by analyzing the differing effects of the complex, multiple, and shifting layers of institutional contexts in which they are embedded.
Characteristics of Left Atrial Deformation Parameters and Their Prognostic Impact in Patients with Pathological Left Ventricular Hypertrophy: Analysis by Speckle Tracking Echocardiography
Authors: Iio Chiharuko , Inoue Katsuji , Nishimura Kazuhisa , Fujii Akira , Nagai Takayuki , Suzuki Jun , Okura Takafumi , Higaki Jitsuo , Ogimoto Akiyoshi
Published: May 2015

Background

The pathological process of left ventricular (LV) hypertrophy is associated with left atrial (LA) remodeling. This study was aimed to evaluate the prognostic value of LA strain parameters in patients with pathological LV hypertrophy.

Methods

This study included 95 patients with hypertensive heart disease (HHD: n = 24), hypertrophic cardiomyopathy (HCM: n = 56), cardiac amyloidosis (CA: n = 15), and control subjects (n = 20). We used two‐dimensional speckle tracking echocardiography (STE) to analyze LA global strain. LA electromechanical conduction time (EMT) at the septal (EMT‐septal) and lateral wall (EMT‐lateral), and their time difference (EMT‐diff) were calculated. The incidence of cardiac death and heart failure hospitalization was defined as major cardiac events and that of atrial fibrillation as secondary outcome.

Results

Left atrial volume index was increased and LA booster strain was decreased in the HCM and CA groups compared with the HHD group. EMT‐lateral was increased in the diseased groups compared with the control. EMT‐diff was prolonged in the CA group compared with the HCM group. During the follow‐up period (mean 3.4 years), major cardiac events and atrial fibrillation occurred in 17 and 13 patients, respectively. The occurrence of atrial fibrillation was associated with CA etiology, E/e′, LA volume index, LAa, and EMT‐lateral. The incidence of major cardiac events was independently correlated with LA volume index and EMT‐diff in multivariate analysis.

Conclusion

This study suggested that the EMT‐diff could discriminate patients with a high risk of cardiac events among patients with pathological LV hypertrophy.
Another biomineralising protostome with an msp130 gene and conservation of msp130 gene structure across Bilateria
Authors: Szabó Réka , Ferrier David E.K.
Published: May 2015

Msp130 genes are known for their association with biomineralisation, principally in echinoderm skeletogenesis. Recently, msp130 genes were shown to exist more widely across the animal kingdom, including in molluscs, and a hypothesis was formed that the genes had arisen independently in the deuterostome and mollusc lineages via horizontal gene transfer, thus facilitating the evolution of biomineralisation in these distinct lineages (Ettensohn, 2014). Here we show that another biomineralising protostome, the polychaete Spirobranchus (formerly Pomatoceros) lamarcki also possesses an msp130 gene, and expresses it during a biomineralisation process. However, based on analysis of gene structure, we hypothesize that the protostome and deuterostome msp130 genes did not originate from independent horizontal gene transfers, but instead are descended from a gene already present in the bilaterian ancestor, with the gene being secondarily lost from several lineages.
The significance and scope of evolutionary developmental biology: a vision for the 21st century
Authors: Moczek Armin P. , Sears Karen E. , Stollewerk Angelika , Wittkopp Patricia J. , Diggle Pamela , Dworkin Ian , Ledon‐Rettig Cristina , Matus David Q. , Roth Siegfried , Abouheif Ehab , Brown Federico D. , Chiu Chi‐Hua , Cohen C. Sarah , Tomaso Anthony W. De , Gilbert Scott F. , Hall Brian , Love Alan C. , Lyons Deirdre C. , Sanger Thomas J. , Smith Joel , Specht Chelsea , Vallejo‐Marin Mario , Extavour Cassandra G.
Published: May 2015

Evolutionary developmental biology (evo‐devo) has undergone dramatic transformations since its emergence as a distinct discipline. This paper aims to highlight the scope, power, and future promise of evo‐devo to transform and unify diverse aspects of biology. We articulate key questions at the core of eleven biological disciplines—from Evolution, Development, Paleontology, and Neurobiology to Cellular and Molecular Biology, Quantitative Genetics, Human Diseases, Ecology, Agriculture and Science Education, and lastly, Evolutionary Developmental Biology itself—and discuss why evo‐devo is uniquely situated to substantially improve our ability to find meaningful answers to these fundamental questions. We posit that the tools, concepts, and ways of thinking developed by evo‐devo have profound potential to advance, integrate, and unify biological sciences as well as inform policy decisions and illuminate science education. We look to the next generation of evolutionary developmental biologists to help shape this process as we confront the scientific challenges of the 21st century.
Young Australians with moderate to severe mental health problems: client data and outcomes at Children and Young People's Mental Health
Authors: Howe Deborah , Batchelor Samantha , Coates Dominiek D.
Published: May 2015

Aim

Almost a quarter of young Australians experience a mental health issue that may become chronic if left untreated. Children and Young People's Mental Health (CYPMH) is a specialist tertiary service for young people with moderate to severe mental health problems on the Central Coast in Australia. This paper presents an overview of client data and service use collected over a 1 year period specific to the Youth Mental Health (YMH) component of the service.

Method

Client data, including demographic characteristics, service usage, presenting issues and standardized outcome measures, were analysed using SPSS. Clinicians routinely collect MH‐OAT (Mental Health Outcomes and Assessment Tools) measures at different points in a client's episode of care, and each of these measures was analysed separately. Wilcoxon Z and a series of McNemar's tests were used to report on the difference between admission and discharge scores.

Results

During a designated 1 year period, 830 referrals to YMH were received. The most prevalent presenting issue was suicidal ideation followed by deliberate self‐harm and depression. A comparison of admission and discharge outcome scores shows significant improvement by discharge on a range of measures. Specifically, analysis identified significant differences between admission and discharge HoNOSCA (Health of the Nation Outcomes Scales for Children and Adolescents) and CGAS (Children's Global Assessment Scale) scores for young people aged 12–17 and HONOS (Health of the Nation Outcomes Scale) scores for young people aged 18–24.

Conclusion

The clinical outcomes for young people are positive with improvements seen on a range of measures.
Tumour‐associated mast cells in classical Hodgkin's lymphoma: correlation with histological subtype, other tumour‐infiltrating inflammatory cell subsets and outcome
Authors: Andersen Maja D. , Kamper Peter , Nielsen Patricia S. , Bendix Knud , Riber‐Hansen Rikke , Steiniche Torben , Hamilton‐Dutoit Stephen , Clausen Michael , d'Amore Francesco
Published: May 2015

The tumour microenvironment in classical Hodgkin's lymphoma (cHL) is characterised by a minor population of neoplastic Hodgkin and Reed–Sternberg cells within a heterogeneous background of non‐neoplastic bystanders cells, including mast cells. The number of infiltrating mast cells in cHL has been reported to correlate with poor prognosis. We used immunohistochemistry to assess the degree of tumour‐infiltrating mast cells in cHL tissue microarrays and correlated this with clinico‐pathological features and prognosis in a cohort of homogeneously treated patients with Hodgkin's disease. A high degree of tumour mast cells was associated with nodular sclerosis (NS) subtype histology (P = 0.0002). Moreover, the number of mast cells was inversely correlated with the numbers of CD68+ and CD163+ macrophages (P = 0.0001 and P = 0.003, respectively) and with the number of granzyme+ cytotoxic cells (P = 0.004). The degree of mast cell infiltration was not a prognostic factor in cHL of nodular sclerosis subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast cells correlated with significantly poorer outcome both in terms of overall (P = 0.03) and event‐free survival (P = 0.01). Further studies are warranted into the biological mechanisms underlying this adverse outcome and their possible therapeutic implications.
Right parietal cortex mediates recognition memory for melodies
Authors: Schaal Nora K. , Javadi Amir‐Homayoun , Halpern Andrea R. , Pollok Bettina , Banissy Michael J.
Published: May 2015

Functional brain imaging studies have highlighted the significance of right‐lateralized temporal, frontal and parietal brain areas for memory for melodies. The present study investigated the involvement of bilateral posterior parietal cortices (PPCs) for the recognition memory of melodies using transcranial direct current stimulation (tDCS). Participants performed a recognition task before and after tDCS. The task included an encoding phase (12 melodies), a retention period, as well as a recognition phase (24 melodies). Experiment 1 revealed that anodal tDCS over the right PPC led to a deterioration of overall memory performance compared with sham. Experiment 2 confirmed the results of Experiment 1 and further showed that anodal tDCS over the left PPC did not show a modulatory effect on memory task performance, indicating a right lateralization for musical memory. Furthermore, both experiments revealed that the decline in memory for melodies can be traced back to an interference of anodal stimulation on the recollection process (remember judgements) rather than to familiarity judgements. Taken together, this study revealed a causal involvement of the right PPC for memory for melodies and demonstrated a key role for this brain region in the recollection process of the memory task.
Differential influence of propofol and isoflurane anesthesia in a non‐human primate on the brain kinetics and binding of [18F]DPA‐714, a positron emission tomography imaging marker of glial activation
Authors: Saba Wadad , Goutal Sébastien , Kuhnast Bertrand , Dollé Frédéric , Auvity Sylvain , Fontyn Yoan , Cayla Jérôme , Peyronneau Marie‐Anne , Valette Héric , Tournier Nicolas
Published: May 2015

Translocator protein 18 kDa (TSPO) expression at the mitochondrial membrane of glial cells is related to glial activation. TSPO radioligands such as [18F]DPA‐714 are useful for the non‐invasive study of neuroimmune processes using positron emission tomography (PET). Anesthetic agents were shown to impact mitochondrial function and may influence [18F]DPA‐714 binding parameters and PET kinetics. [18F]DPA‐714 PET imaging was performed in Papio anubis baboons anesthetized using either intravenous propofol (n = 3) or inhaled isoflurane (n = 3). Brain kinetics and metabolite‐corrected input function were measured to estimate [18F]DPA‐714 brain distribution (VT). Displacement experiments were performed using PK11195 (1.5 mg/kg). In vitro [18F]DPA‐714 binding experiments were performed using baboon brain tissue in the absence and presence of tested anesthetics. Brain radioactivity peaked higher in isoflurane‐anesthetized animals compared with propofol (SUVmax = 2.7 ± 0.5 vs. 1.3 ± 0.2, respectively) but was not different after 30 min. Brain VT was not different under propofol and isoflurane. Displacement resulted in a 35.8 ± 8.4% decrease of brain radioactivity under propofol but not under isoflurane (0.1 ± 7.0%). In vitro, the presence of propofol increased TSPO density and dramatically reduced its affinity for [18F]DPA‐714 compared with control. This in vitro effect was not significant with isoflurane. Exposure to propofol and isoflurane differentially influences TSPO interaction with its specific radioligand [18F]DPA‐714 with subsequent impact on its tissue kinetics and specific binding estimated in vivo using PET. Therefore, the choice of anesthetics and their potential influence on PET data should be considered for the design of imaging studies using TSPO radioligands, especially in a translational research context.
Features of cardioembolic stroke with persistent and paroxysmal atrial fibrillation – a study with the Japan Stroke Registry
Authors: Deguchi I. , Hayashi T. , Fukuoka T. , Kobayashi S. , Tanahashi N. ,   Japan Standard Stroke Registry Study Group
Published: May 2015

Background and purpose

The stroke severity on admission and clinical outcomes were compared between ischaemic stroke patients with non‐valvular atrial fibrillation (NVAF) of the persistent (PeAF) and paroxysmal (PAF) types.

Methods

The study comprised 9293 patients with cardioembolic stroke and NVAF who were registered in the Japanese stroke databank: 6522 had PeAF (70.2%) and 2771 had PAF (29.8%). Stroke severity on admission and the clinical outcomes on discharge were retrospectively compared between these patient groups.

Results

The National Institutes of Health Stroke Scale score on admission (median, interquartile range) was 10 (3–20) for PeAF patients and 7 (2–17) for PAF patients, indicating that stroke severity on admission was significantly worse in PeAF patients than PAF patients (P < 0.001). Good outcomes (modified Rankin scale score ≤2) were achieved by 45% PeAF patients and 53% PAF patients. Thus, PeAF patients had significantly poorer clinical outcomes than PAF patients (P < 0.001). In‐hospital mortality was significantly higher amongst PeAF patients (11%) than PAF patients (8%) (P < 0.001). Multivariate analysis of factors contributing to clinical outcomes showed that PeAF was a contributing factor for in‐hospital mortality (odds ratio 1.261; 95% confidence interval 1.011–1.652; P = 0.045).

Conclusions

Amongst cardioembolic stroke patients with NVAF, those with PeAF have significantly higher stroke severity on admission than those with PAF, and PeAF is a factor contributing to in‐hospital mortality. Thus, our study suggests that the type of atrial fibrillation affects stroke severity and clinical outcomes following cerebral infarction.