bluuebunny/crossref_metadata_2025 huggingface dataset:
The growing scale and scope of the supply chain: a reflection on supply chain graduate skills
Authors: Jordan Christine , Bak Ozlem
Published: September 2016

Purpose

The growing scale and scope of the supply chain requires a greater understanding of the broader supply chain skills picture. This study aims to assess the supply chain skills needs within the context of a UK-based higher education institution involving graduates, academics and employers to appreciate the graduate skills demands of modern supply chains.

Design/methodology/approach

A mixed methods study entailing in-depth interviews with academics followed by a questionnaire distributed to graduates and employers has been designed and utilised.

Findings

The findings indicate that the changing supply chain scope encourages the requisition and development of different supply chain skills with varied levels of emphases in relation to 25 skills identified in the literature. Key graduate skills needs are highlighted, including time management, collaborative learning, teamwork and problem solving, with the addition of two supply chain skill areas, namely specialist training and the understanding and application of regulations. The findings of the current study present a limited emphasis on information technology (IT) skills, despite the significant IT advancements and changes in supply chains.

Research limitations/implications

The study has been carried out in a UK university delivering undergraduate supply chain management courses. It would be beneficial to test whether the findings are exemplary across other supply chain courses and to investigate the integration of these skills within the supply chain syllabus and how employers, graduates and academic parties could actively engage in developing the agenda for future supply chain skills needs.

Practical implications

This research paper highlights the gaps in supply chain skills, which inevitably puts considerable pressure on operatives and managers whose responsibility it is to ensure compliance with regulations and professional bodies.

Originality/value

This paper contributes to the supply chain skills discussion and reports subject relevant challenges for supply chain educators by engaging three key stakeholders – graduate employers, graduates and academics. The findings have generated additional supply chain skills to the academic literature, in addition to providing an understanding of the weighting of skills in terms of their importance and application to industry needs.
Multi‐stressed families, child violence and the larger system: an adaptation of the nonviolent model
Authors: Jakob Peter
Published: September 2016

Non Violent Resistance (NVR) aims to change family relationships, when children and young people show violent, aggressive or self‐destructive behaviour. Trauma in multi‐stressed families necessitates an adaptation of the original NVR approach in order to meet these clients' specific therapeutic needs when child violence arises. The author has developed such an adaptation. This article gives an overview of the larger system aspect of the adapted NVR model, illustrating how NVR core principles are applied to help family members develop a sense of safety within the larger system, so the nuclear family itself can become a safe and supportive recovery environment.

Practitioner points

By differentiating between interaction patterns, parents identify safe supporters within the larger system to help develop effective responses to harmful child behaviour

Therapeutic conversation centres parents’ own formulation of their support needs, in order to regain their voice and experience personal agency

Effective resistance to problem behaviour grows by engaging other adults in ways that facilitate parents’ access to internal and interpersonal resources
Therapeutic Apheresis in Hematologic, Autoimmune and Dermatologic Diseases With Immunologic Origin
Authors: Bambauer Rolf , Latza Reinhard , Burgard Daniel , Schiel Ralf
Published: September 2016

The process of curing a patient by removing his illness by extracting blood is a very old one. Many years ago, phlebotomy was practiced to cure illness. Now, this old process, placed on a rational basis with therapeutic apheresis (TA), is being followed in clinical practice. Therapeutic plasma exchange (TPE) with hollow fiber modules has been used in different severe diseases for more than 40 years. Based on many years of experience with the extracorporeal circulation in end‐stage renal disease, the authors herein give an overview of TA in immunological diseases, especially in hematologic, autoimmune and dermatologic diseases. Updated information on immunology and molecular biology of different immunological diseases is discussed in relation to the rationale for apheresis therapy and its place in combination with other modern therapies. With the introduction of novel and effective biologic agents, TA is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved in recent years, due in part to very aggressive therapy schemes. For the immunological diseases that can be treated with TA, the guidelines of the German Working Group of Clinical Nephrology and of the Apheresis Applications Committee of the American Society for Apheresis are cited. TA has been shown to effectively remove the autoantibodies from blood and lead to rapid clinical improvement.
Attitudes towards and experiences with research: Differences between dietetics students and professionals in Australia and the United States
Authors: Tan Sze‐Yen , Hemmelgarn Megan , Baumgardner Kelli , Tucker Robin M.
Published: September 2016

Aim

Research conducted by dietitians is encouraged by national and international organisations, yet research output remains low. The attitudes towards and experiences with research and research methods course work of students and practitioners in Australia and the United States were examined.

Methods

A cross‐sectional online survey was conducted. Participants were contacted by email; 173 Australian (N = 50 students; 123 practitioners) and 499 US (N = 231 students; 268 practitioners) respondents completed the survey.

Results

A smaller proportion of American students (74%) indicated that they would consider conducting research in the future compared to Australian students (84%) (P < 0.001). More Australian than American practitioners indicated interest in conducting research in their current position (87% vs 66%; P < 0.001). Research training did not increase future research plans, but respondents who had conducted research either as a student or at work responded more favourably to conducting research in the future (P < 0.001). In general, Australian respondents were more supportive of and more experienced with research.

Conclusions

Unlike classroom training, past research experiences supported plans for future research. Further work needs to investigate how the culture of the profession can be changed to support more dietitian‐conducted research.
Release Kinetics of Nisin from Chitosan–Alginate Complex Films
Authors: Chandrasekar Vaishnavi , Coupland John N. , Anantheswaran Ramaswamy C.
Published: September 2016

Understanding the release kinetics of antimicrobials from polymer films is important in the design of effective antimicrobial packaging films. The release kinetics of nisin (30 mg/film) from chitosan–alginate polyelectric complex films prepared using various fractions of alginate (33%, 50%, and 66%) was investigated into an aqueous release medium. Films containing higher alginate fractions showed significantly lower (P < 0.05) degree of swelling in water. Total amount of nisin released from films into an aqueous system decreased significantly (P < 0.05) with an increase in alginate concentration. The mechanism of diffusion of nisin from all films was found to be Fickian, and diffusion coefficients varied from 0.872 × 10−9 to 8.034 ×10−9 cm2/s. Strong complexation was confirmed between chitosan and alginate polymers within the films using isothermal titration calorimetry and viscosity studies, which affects swelling of films and subsequent nisin release. Complexation was also confirmed between nisin and alginate, which limited the amount of free nisin available for diffusion from films. These low‐swelling biopolymer complexes have potential to be used as antimicrobial packaging films with sustained nisin release characteristics.
The role of birth cohorts in long‐term trends in liver cirrhosis mortality across eight European countries
Authors: Trias‐Llimós Sergi , Bijlsma Maarten J. , Janssen Fanny
Published: September 2016

Background and aims

Understanding why inequalities in alcohol‐related mortality trends by sex and country exist is essential for developing health policies. Birth cohort effects, indicative of differences by generation in drinking, have rarely been studied. This study estimated the relative contributions of birth cohorts to liver cirrhosis mortality trends and compared sex‐ and country‐specific cohort patterns across eight European countries.

Design

Time–series analysis of population‐level mortality data.

Setting

Austria, Finland, Hungary, Italy, the Netherlands, Poland, Spain and Sweden; 1950–2011.

Participants

National populations aged 15–94 years.

Measurements

We modelled country‐ and sex‐specific liver cirrhosis mortality (from national vital registers) adjusting for age, period and birth cohort.

Findings

Birth cohorts (adjusted for age and period) made statistically significant contributions to liver cirrhosis mortality in all countries and for both sexes (P < 0.001), and more so among women (average contribution to deviance reduction of 38.8%) than among men (17.4%). The observed cohort patterns were statistically different between all but two country pairs (P < 0.001). Sex differences existed overall (P < 0.001), but not in the majority of countries (P > 0.999). Visual inspection of birth cohort patterns reveals birth cohorts at higher risk of liver cirrhosis mortality.

Conclusions

The inclusion of the birth cohort dimension improves the understanding of alcohol‐attributable mortality trends in Europe. Birth cohorts at higher risk of liver cirrhosis mortality were born during 1935–49 in Sweden and Finland, around 1950 in Austria and the Netherlands and 1960 or later in Hungary, Italy, Poland and Spain.
The Globalization of Ayahuasca Shamanism and the Erasure of Indigenous Shamanism
Authors: Fotiou Evgenia
Published: September 2016

Ayahuasca is a hallucinogenic plant mixture used in a ceremonial context throughout western Amazonia, and its use has expanded globally in recent decades. As part of this expansion, ayahuasca has become popular among westerners who travel to the Peruvian Amazon in increasing numbers to experience its reportedly healing and transformative effects. Drawing from ethnographic fieldwork in and around the area of Iquitos, Peru, the epicenter of ayahuasca tourism, this paper focuses on some of the problematic aspects of western engagement with indigenous spiritual traditions. This engagement is usually based on idealized and romanticized notions of indigenous shamanism and an inability to digest its less palatable aspects, such as sorcery. Through ethnographic examples and ethnohistorical evidence, I show that the romanticization indigenous peoples is not benign. In fact, this one‐sided romantic image hides the complexity of indigenous peoples’ situations by erasing the injustices that they have experienced and continue to experience. I propose a more holistic approach to ayahuasca shamanism that views indigenous peoples not living in a fictitious harmony with nature but as people embedded in larger struggles and facing important challenges not the least of which is the recent commercialization of indigenous spirituality.
Ayahuasca and Sumak Kawsay: Challenges to the Implementation of the Principle of “Buen Vivir,” Religious Freedom, and Cultural Heritage Protection
Authors: Irigaray Carlos Teodoro J. H. , Girard Pierre , Irigaray Maíra , da Silva Carolina Joana
Published: September 2016

The current environmental crisis can be approached, through many perspectives, as a civilizational crisis. Alternatives of human transcendence are identified in the Inca civilization to compensate for the malaise that characterizes the actual crisis. There is a multicultural dimension to the manifestations of Hoasca (or Ayahuasca) occurring in Amazonian countries. As employed by the Beneficent Spiritist Center União do Vegetal (UDV) in a religious context, it can contribute to the reconstruction of buen vivir (or in Quechua, sumak kawsay, meaning complete wellness), which served as the principle of the civilizations that preceded the colonization of the Americas by Europeans. Today, the State openly confronts the manifestation of the constitutional principles of buen vivir, religious freedom, and the protection of this cultural heritage. Here, the implications of the civilizational crisis and ways of overcoming it are approached from the standpoint of deep ecology, but the implications also reflect the doctrinal vision of the UDV to which the authors are affiliated.
Ayahuasca Treatment Center Safety for the Western Seeker
Authors: Ray Raven Renèe , Lassiter Kerry S.
Published: September 2016

Ayahuasca, an ancient Amazonian psychedelic tea traditionally used ceremonially among indigenous peoples, has recently become known as a possible treatment for a wide range of disorders. The awareness of this sacred medicine has grown exponentially over the past decade, attracting westerners from a wide variety of backgrounds, hoping to find treatment for a myriad of emotional and physical illnesses, as well as spiritual needs. In the wake of the commercialization and westernization of the use of ayahuasca, and the subsequent proliferation of ayahuasca treatment centers, this paper examines the benefits and possible risks of this form of therapy in an effort to create a safety protocol for Westerners in this context. The most practical approach to increasing safety for Westerners attending these Amazonian treatment centers is to educate the seeker prior to treatment and to provide access to specialized therapeutic aftercare services.
Systematic review with meta‐analysis: fundic gland polyps and proton pump inhibitors
Authors: Martin F. C. , Chenevix‐Trench G. , Yeomans N. D.
Published: September 2016

Background

A causal association between proton pump inhibitor (PPI) use and fundic gland polyps has been suggested, but the data are conflicting.

Aim

To clarify the relationship through a meta‐analysis of the existing data.

Methods

A systematic retrieval and selection of records was performed. The main inclusion criteria were original studies reporting the prevalence of fundic gland polyps in PPI users or the reverse, compared to controls. Key outcomes were the odds ratios (OR) for fundic gland polyp prevalence in association with PPI use, prevalence of PPI use amongst subjects with fundic gland polyps and fundic gland polyp prevalence among PPI users. Statistical analysis was performed using Mix 2.0 Pro.

Results

The initial search using electronic databases and manual searching retrieved 339 peer‐reviewed articles and abstracts. Twenty articles met all inclusion and exclusion criteria, with a total of 40 218 subjects included. The meta‐analysis of 12 studies revealed an increase in fundic gland polyps amongst PPI users compared to controls (OR 2.46, 95% CI 1.42–4.27,P = 0.001), particularly among individuals taking PPIs for at least 6 months (OR: 4.71, 95% CI 2.22–9.99,P < 0.001) or 12 months (OR: 5.32, 95% CI 2.58–10.99,P < 0.001).

Conclusions

Proton pump inhibitor usage is associated with a significantly increased prevalence of fundic gland polyps, and there is a trend for this to increase with longer length of PPI exposure. However, the meta‐analysis is limited mainly to cohort studies.
Establishment of MAGEC2‐knockout cells and functional investigation of MAGEC2 in tumor cells
Authors: Wang Jingjing , Song Xiao , Guo Chengli , Wang Ying , Yin Yanhui
Published: September 2016

Cancer/testis antigen MAGEC2, a member of the type I melanoma‐associated antigen family, is expressed in a wide variety of cancer types but not in normal somatic cells. MAGEC2 has long been recognized as a tumor‐specific target, however, its functions remain largely unknown. In this study, we established MAGEC2‐knockout A375 melanoma cell lines using the CRISPR/Cas9 system. Seven clonal cell lines were generated by using four single guide RNAs targeting the coding region of the MAGEC2 gene, which produced indels that abolished MAGEC2 protein expression. To identify the differentially expressed protein profiles associated with MAGEC2 loss, isobaric tag for relative quantitation‐based comparative proteomics experiments were carried out on the MAGEC2‐knockcout and control A375 cells. Mining of the proteomics data identified a total 224 (61.6% upregulated and 38.4% downregulated) proteins to be significantly altered in expression level in MAGEC2‐knockcout cells. Ingenuity Pathway Analysis indicated that the significantly altered proteins were involved in critical neoplasia‐related biological functions such as cell death, proliferation, and movement. Gene ontology analysis identified “apoptosis signaling” as the top‐most upregulated pathway associated with MAGEC2 loss. We showed that knockout or knockdown of the MAGEC2 gene sensitized melanoma cells to tumor necrosis factor‐α‐induced apoptosis. Interestingly, actin‐based motility by Rho and RhoA signaling, known to promote cell migration, were also identified as the top downregulated pathways in MAGEC2‐knockout A375 cells. In short, our study provides a suitable cell model for exploring the biological functions of MAGEC2 in malignant cells, and sheds light on the molecular pathway by which MAGEC2 promotes tumor development.
Feasibility of the Participatory Experience Survey and the Setting Affordances Survey for use in evaluation of programmes serving youth with intellectual and developmental disabilities
Authors: Liljenquist K. , Coster W. , Kramer J. , Rossetti Z.
Published: September 2016

Background

Participation by youth with disabilities in recreational activities has been shown to promote the development of important skills needed for transition to adulthood. The Participatory Experience Survey (PES) and the Setting Affordances Survey (SAS) were developed for use by recreational programmes serving youth with significant intellectual and developmental disabilities (SIDD) to assess participant experiences and ensure that participants are afforded optimal opportunities to develop these skills. This paper presents a feasibility evaluation to determine the appropriateness of the PES and the SAS for use in a programme evaluation context.

Method

The PES and the SAS were used to evaluate a programme serving youth with SIDD in the greater northwest region of the United States. Three recreational activities were evaluated: an art project, trip to a zoo and a track practice. Programme volunteers used the SAS to assess opportunities and affordances offered within each activity. The PES was then given to 10 young people in each activity to capture their experiences. It was hypothesized that each setting would afford different experiences and developmental opportunities because of the differing nature of the activities.

Results

The PES and SAS were found to be feasible for conducting a programme evaluation. All three settings offered varying types of experiences and affordances. Notably, as measured by the SAS, opportunity for skill development was greater in more structured activities; the zoo had the fewest opportunities for skill development and the art project had the most skill development opportunities. Youth answered ‘no’ most often to ‘asking for help’ and ‘helping a kid’, suggesting changes to offer more opportunities to develop these skills would be beneficial in all three activities.

Conclusion

These new instruments offer programmes a means to more fully include young people with disabilities during programme evaluations, leading to better‐structured, more supportive programmes.
Patterns of simultaneous patch test reactions to thiurams and dithiocarbamates in 164 patients
Authors: Aalto‐Korte Kristiina , Pesonen Maria
Published: September 2016

Background

Thiurams and dithiocarbamates are structurally related sensitizing rubber accelerators.

Objectives

To study patterns of simultaneous patch test reactions to thiurams and dithiocarbamates at the Finnish Institute of Occupational Health in 1991–2015.

Methods

We searched the patch test files for patients with allergic reactions to thiuram mix, its four components, and three dithiocarbamates, and analysed patterns of simultaneous reactions to these test substances.

Results

We found 155 patients who reacted positively to at least one thiuram or dithiocarbamate in the rubber chemical series. Thirty‐four (22%) of these patients reacted positively to some dithiocarbamate derivatives. Twenty‐one reacted positively to zinc dimethyldithiocarbamate, 20 to zinc diethyldithiocarbamate, and 1 to zinc dibutyldithiocarbamate. All dithiocarbamate‐allergic patients reacted positively to some thiurams, and their thiuram reactions were often strong or extreme positive. Nine thiuram mix reactions turned out to be false‐positive reactions, without reactions to the constituents, and 24 patients showed false‐negative reactions to thiuram mix during the same time period.

Conclusions

Dithiocarbamate contact allergy was always connected to thiuram allergy. Screening dithiocarbamate allergy with carba mix thus appears to be unnecessary, but ways to improve the present thiuram mix should be investigated. Meanwhile, individual thiurams are best for diagnosing contact allergy to these accelerators.
Cardiac computed tomography of an asymptomatic 48‐year‐old woman with ALCAPA syndrome
Authors: Sajjadieh khajouei Amirreza , Samie‐Nasab Mohammadreza , Behjati Mohaddeseh , Biederman Robert W.
Published: September 2016

Untreated ALCAPA cases most often die in infancy. Adults with untreated ALCAPA commonly present with mitral regurgitation, severe left ventricular dysfunction, and sometimes myocardial infarction. Herein, we present an asymptomatic adult female with ALCAPA recognized through cardiac computed tomography (CT). In ALCAPA, like other coronary anomalies, cardiac CT is often instrumental in providing unique noninvasive and clinically relevant evaluation. Herein, we present an atypical presentation of an asymptomatic middle‐aged adult female with ALCAPA.
Hyperuricemia protects against low bone mineral density, osteoporosis and fractures: a systematic review and meta‐analysis
Authors: Veronese Nicola , Carraro Sara , Bano Giulia , Trevisan Caterina , Solmi Marco , Luchini Claudio , Manzato Enzo , Caccialanza Riccardo , Sergi Giuseppe , Nicetto Davide , Cereda Emanuele
Published: September 2016

Background

Serum uric acid (SUA) accounts for about 50% of extracellular antioxidant activity, suggesting that hyperuricemia may have a protective role in diseases characterized by high levels of oxidative stress, such as osteoporosis. We aimed to meta‐analyse data regarding bone mineral density (BMD), osteoporosis and fractures in people with higher SUA vs. lower SUA concentrations.

Materials and methods

Two investigators conducted a literature search using PubMed and Scopus, without language restrictions. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used for BMD; risk ratios (RRs) and adjusted odds ratios (ORs) for cross‐sectional data. Most possible adjusted hazard ratios (HRs) were used to assess the association between baseline SUA and incident fractures.

Results

Of 1405 initial hits, 19 studies were eligible including a total of 55 859 participants. Subjects with higher SUA levels had significantly higher BMD values for the spine (six studies; SMD = 0·29; 95% CI: 0·22–0·35; I2 = 47%), total hip (seven studies; SMD = 0·29; 95% CI: 0·24–0·34; I2 = 33%) and femoral neck (six studies; SMD = 0·25; 95% CI: 0·16–0·34; I2 = 71%). Simple correlation analyses substantially confirmed these findings. An increase of one standard deviation in SUA levels reduced the number of new fractures at follow‐up (three studies; HR = 0·83; 95% CI: 0·74–0·92; I2 = 0%). No significant differences between men and women emerged, although data about women were limited.

Conclusions

Hyperuricemia was found independently associated with BMD and fractures, supporting a protective role for uric acid in bone metabolism disorders.
Default mode network changes in multiple sclerosis: a link between depression and cognitive impairment?
Authors: Bonavita S. , Sacco R. , Esposito S. , d'Ambrosio A. , Della Corte M. , Corbo D. , Docimo R. , Gallo A. , Lavorgna L. , Cirillo M. , Bisecco A. , Esposito F. , Tedeschi G.
Published: September 2016

Background and purpose

In multiple sclerosis (MS), depression is a common disorder whose pathophysiology is still debated. To gain insights into the pathophysiology of depression in MS, resting‐state (RS) functional connectivity (FC) changes of the default mode network (DMN), salience network (SN) and executive control network (ECN) were assessed in a group of depressed MS (D‐MS) patients and in appropriately matched control groups.

Methods

Sixteen D‐MS patients, 17 non‐depressed MS (ND‐MS) patients, 17 non‐depressed healthy controls and 15 depressed subjects (D‐S), age, sex and education matched, cognitively preserved and non‐fatigued, were enrolled. All participants underwent a neuropsychological evaluation and RS functional magnetic resonance imaging study.

Results

Comparing D‐MS patients with D‐S, within the DMN, a significant RS‐FC suppression was found in the posterior cingulate cortex (PCC); comparing D‐MS with ND‐MS, FC was significantly increased in the anterior cingulate cortex and significantly reduced in the PCC. Within the SN increased FC in the right supramarginal gyrus and right middle frontal gyrus was found in D‐MS patients compared to D‐S and to ND‐MS; within the ECN increased FC in the right inferior parietal cortex was found in D‐MS patients compared to ND‐MS patients.

Conclusions

In cognitively preserved D‐MS patients, FC derangement occurs in the SN, ECN and DMN. In the latter, changes occurring both in the anterior cingulate cortex and PCC suggest that depression in MS may be linked to MS itself and, in particular, to a peculiar pattern of network abnormalities favored by MS pathology through disconnection mechanisms. Reduced FC in the PCC, similar to MS patients with cognitive impairment, suggests a functional link between depression and cognitive impairment in MS.
Does Paid Maternity Leave Affect Infant Development and Second‐Birth Intentions?
Authors: Hwang Woosang , Jung Eunjoo
Published: September 2016

Given the economic implications of a low‐fertility rate, many countries have implemented paid maternity leave to promote births. However, the efficacy of this policy is mostly unknown. We examined whether paid maternity leave in South Korea, which has a fertility rate among the lowest in the world, is directly related to infant development and employed mothers' second‐birth intentions, and indirectly associated with these outcomes via parenting stress. Participants included 315 married and employed Korean mothers in the months after giving birth to their first child. Paid maternity leave was beneficial for infant development but was not a solution for promoting second‐birth intentions among employed mothers in Korea. Parenting stress adversely affected both infant development and employed mothers' second‐birth intentions, and it may therefore need to be considered as work–family policies, fertility issues, and infant development in families are addressed. Implications considering cultural and familial contexts are discussed.
Human DP and EP2 prostanoid receptors take on distinct forms depending on the diverse binding of different ligands
Authors: Suganami Akiko , Fujino Hiromichi , Okura Iori , Yanagisawa Naoki , Sugiyama Hajime , Regan John W. , Tamura Yutaka , Murayama Toshihiko
Published: September 2016

Human D‐type prostanoid (DP) and E‐type prostanoid 2 (EP2) receptors are G protein‐coupled receptors and are regarded as the most closely related receptors among prostanoid receptors because they are generated by tandem duplication. The DP receptor‐cognate ligand, prostaglandin D2 (PGD2) has the ability to activate not only DP receptors but also EP2 receptors. Likewise, the EP2 receptor‐cognate ligand, prostaglandin E2 (PGE2) has the ability to activate DP receptors in addition to EP receptors in order to stimulate cAMP formation. However, since PGD2 and/or PGE2 activate DP and EP2 receptors to similar maximal levels, that is, their similar efficacies, differences between the ligands in each receptor have not yet been determined in detail except for their different affinities. Herein we demonstrated, using an in silico simulation to predict binding patterns among DP or EP2 receptors and PGD2, PGE2, or prostaglandin F2α as the reference prostanoid, that DP and EP2 receptors plausibly take on distinct forms depending on the diverse binding of different ligands. Since these ligands have the potential to make these receptors form distinct conformations with discrete signaling pathways, they are consequently regarded as endogenous biased ligands. Moreover, by using functional assays, the susceptibilities of the DP receptors to the noncognate ligands were approximately 10 times lower than those of EP2 receptors. Thus, EP2 receptors seem to be able to distinguish endogenous ligands better than DP receptors, thereby both receptors are plausibly gaining role‐sharing functions with respect to one another as the copies of duplicated gene.
The influence of angiotensin converting enzyme mutations on the kinetics and dynamics of N‐domain selective inhibition
Authors: Lubbe Lizelle , Sewell Brian T. , Sturrock Edward D.
Published: September 2016

Angiotensin‐1‐converting enzyme (ACE) is a zinc metalloprotease that plays a major role in blood pressure regulation via the renin–angiotensin–aldosterone system. ACE consists of two domains with differences in inhibitor binding affinities despite their 90% active site identity. While the C‐domain primarily controls blood pressure, the N‐domain is selective for cleavage of the antifibrotic N‐acetyl‐Ser–Asp–Lys–Pro. Inhibitors, such as 33RE, that selectively bind to the N‐domain thus show potential for treating fibrosis without affecting blood pressure. The aim of this study was to elucidate the molecular mechanism of this selectivity. ACE inhibition by 33RE was characterized using a continuous kinetic assay with fluorogenic substrate. The N‐domain displayed nanomolar (Ki = 11.21 ± 0.74 nm) and the C‐domain micromolar (Ki = 11 278 ± 410 nm) inhibition, thus 1000‐fold selectivity. Residues predicted to contribute to selectivity based on the N‐domain‐33RE co‐crystal structure were subsequently mutated to their C‐domain counterparts. S2 subsite mutation with resulting loss of a hydrogen bond drastically decreased the affinity (Ki = 2 794 ± 156 nm), yet did not entirely account for selectivity. Additional substitution of all unique S2′ residues, however, completely abolished selectivity (Ki = 10 009 ± 157 nm). Interestingly, these residues do not directly bind 33RE. All mutants were therefore subjected to molecular dynamics simulations in the presence and absence of 33RE. Trajectory analyses highlighted the importance of these S2′ residues in formation of a favourable interface between the ACE subdomains and thus a closed, ligand‐bound complex. This study provides a molecular basis for the intersubsite synergism governing 33RE's 1000‐fold N‐selectivity and aids the future design of novel inhibitors for fibrosis treatment.

Enzymes

Angiotensin converting enzyme (ACE, EC 3.4.15.1).
Multi‐trophic impacts of an invasive aquatic plant
Authors: Kuehne Lauren M. , Olden Julian D. , Rubenson Erika S.
Published: September 2016

Natural resource agencies are increasingly required to prioritise management of multiple non‐native aquatic plants (macrophytes) in freshwater ecosystems. Characterising the consequences of invasions for ecological processes and corresponding ecosystem services is fundamental to this decision‐making process, but requires an understanding of impacts across physical, chemical, and biological responses.

Accordingly, we evaluated the multi‐trophic impacts of the invasive macrophyte Myriophyllum aquaticum (Haloragaceae; parrotfeather) along the mainstem Chehalis River, Washington, U.S.A. We examined invertebrate, plant and fish community responses to varying degrees of parrotfeather abundance and simultaneously characterised variation in physical structure and dissolved oxygen (DO) across the dominant native and non‐native plant species.

DO concentrations were significantly reduced and approached hypoxic levels in areas dominated by parrotfeather compared with native vegetation. Increased structural complexity, volume and biomass of parrotfeather was associated with increased diversity of epiphytic invertebrates. However, these more diverse invertebrate assemblages were dominated by amphipods, whereas native macrophytes were characterised by cladocerans, chironomids and gastropods. Non‐native fishes (primarily centrarchid species) were more strongly associated with sites where parrotfeather was present and diversity of non‐native fishes was positively correlated along a gradient of parrotfeather abundance. Native fish associated with parrotfeather areas were those that tend to be tolerant of degraded or lower quality habitats.

We saw little evidence of exclusion of other macrophytes; native and non‐native plant diversity and abundance were positively correlated with the parrotfeather gradient. This may reflect that analysis was done at a site level, and competitive dominance might be apparent by changes in species richness at smaller (plot) scales or over longer periods. Alternatively, parrotfeather may demonstrate minimal effects on native plant composition.

Given the effects observed across multiple habitat characteristics and biota, parrotfeather appears to be a highly impactful invader where it establishes. Many of the changes we observed appear to derive from the emergent leaves and dense mat formation of parrotfeather compared with a submersed structure more typical of the native community. Our results suggest that managers should specifically consider contrasting characteristics between non‐native and native physical structure when assessing and prioritising threats of invasive macrophytes.
Ciliate community structure and interactions within the planktonic food web in two alpine lakes of contrasting transparency
Authors: Kammerlander Barbara , Koinig Karin A. , Rott Eugen , Sommaruga Ruben , Tartarotti Barbara , Trattner Florian , Sonntag Bettina
Published: September 2016

Climate warming is accelerating the retreat of glaciers and recently, many ‘new’ glacial turbid lakes have been created. In the course of time, the loss of the hydrological connectivity to a glacier causes, however, changes in their water turbidity and turns these ecosystems into clear ones.

To understand potential differences in the food‐web structure between glacier‐fed turbid and clear alpine lakes, we sampled ciliates, phyto‐, bacterio‐ and zooplankton in one clear and one glacial turbid alpine lake, and measured key physicochemical parameters. In particular, we focused on the ciliate community and the potential drivers for their abundance distribution.

In both lakes, the zooplankton community was similar and dominated by the copepod Cyclops abyssorum tatricus and rotifers including Polyarthra dolichoptera, Keratella hiemalis, Keratella cochlearis and Notholca squamula. The phytoplankton community structure differed and it was dominated by the planktonic diatom Fragilaria tenera and the cryptophyte alga Plagioselmis nannoplanctica in the glacial turbid lake, while chrysophytes and dinoflagellates were predominant in the clear one.

Ciliate abundance and richness were higher in the glacial turbid lake (∼4000–27 800 Ind L−1, up to 29 species) than in the clear lake (∼570–7150 Ind L−1, up to eight species). The dominant species were Balanion planctonicum, Askenasia cf. chlorelligera, Urotricha cf. furcata and Mesodinium cf. acarus. The same species dominated in both lakes, except for Mesodinium cf. acarus and some particle‐associated ciliates, which occurred exclusively in the glacial turbid lake. The relative underwater solar irradiance (i.e. percentage of PAR and UVR at depth) significantly explained their abundance distribution pattern, especially in the clear water lake. In the glacial turbid lake, the abundance of the dominating ciliate taxa was mainly explained by the presence of predatory zooplankton.

Our results revealed an unexpected high abundance and richness of protists (algae, ciliates) in the glacial turbid lake. This type of lake likely offers more suitable environmental conditions and resource niches for protists than the clear and highly UV transparent lake.
Atmospheric CO2 enrichment and drought stress modify root exudation of barley
Authors: Calvo Olga C. , Franzaring Jürgen , Schmid Iris , Müller Matthias , Brohon Nolwenn , Fangmeier Andreas
Published: September 2016

Rising CO2 concentrations associated with drought stress is likely to influence not only aboveground growth, but also belowground plant processes. Little is known about root exudation being influenced by elements of climate change. Therefore, this study wanted to clarify whether barley root exudation responds to drought and CO2 enrichment and whether this reaction differs between an old and a recently released malting barley cultivar. Barley plants were grown in pots filled with sand in controlled climate chambers at ambient (380 ppm) or elevated (550 ppm) atmospheric [CO2] and a normal or reduced water supply. Root exudation patterns were examined at the stem elongation growth stage and when the inflorescences emerged. At both dates, root exudates were analyzed for different compounds such as total free amino acids, proline, potassium, and some phytohormones. Elevated [CO2] decreased the concentrations in root exudates of some compounds such as total free amino acids, proline, and abscisic acid. Moreover, reduced water supply increased proline, potassium, electric conductivity, and hormone concentrations. In general, the modern cultivar showed higher concentrations of proline and abscisic acid than the old one, but the cultivars responded differentially under elevated CO2. Plant developmental stage had also an impact on the root exudation patterns of barley. Generally, we observed significant effects of CO2 enrichment, watering levels, and, to a lesser extent, cultivar on root exudation. However, we did not find any mitigation of the adverse effects of drought by elevated CO2. Understanding the multitude of relationships within the rhizosphere is an important aspect that has to be taken into consideration in the context of crop performance and carbon balance under conditions of climate change.
Disturbances catalyze the adaptation of forest ecosystems to changing climate conditions
Authors: Thom Dominik , Rammer Werner , Seidl Rupert
Published: September 2016

The rates of anthropogenic climate change substantially exceed those at which forest ecosystems – dominated by immobile, long‐lived organisms – are able to adapt. The resulting maladaptation of forests has potentially detrimental effects on ecosystem functioning. Furthermore, as many forest‐dwelling species are highly dependent on the prevailing tree species, a delayed response of the latter to a changing climate can contribute to an extinction debt and mask climate‐induced biodiversity loss. However, climate change will likely also intensify forest disturbances. Here, we tested the hypothesis that disturbances foster the reorganization of ecosystems and catalyze the adaptation of forest composition to climate change. Our specific objectives were (i) to quantify the rate of autonomous forest adaptation to climate change, (ii) examine the role of disturbance in the adaptation process, and (iii) investigate spatial differences in climate‐induced species turnover in an unmanaged mountain forest landscape (Kalkalpen National Park, Austria). Simulations with a process‐based forest landscape model were performed for 36 unique combinations of climate and disturbance scenarios over 1000 years. We found that climate change strongly favored European beech and oak species (currently prevailing in mid‐ to low‐elevation areas), with novel species associations emerging on the landscape. Yet, it took between 357 and 706 years before the landscape attained a dynamic equilibrium with the climate system. Disturbances generally catalyzed adaptation and decreased the time needed to attain equilibrium by up to 211 years. However, while increasing disturbance frequency and severity accelerated adaptation, increasing disturbance size had the opposite effect. Spatial analyses suggest that particularly the lowest and highest elevation areas will be hotspots of future species change. We conclude that the growing maladaptation of forests to climate and the long lead times of autonomous adaptation need to be considered more explicitly in the ongoing efforts to safeguard biodiversity and ecosystem services provisioning.
Choosing outcome assessment tools in haemophilia care and research: a multidisciplinary perspective
Authors: Fischer K. , Poonnoose P. , Dunn A. L. , Babyn P. , Manco‐Johnson M. J. , David J. A. , van der Net J. , Feldman B. , Berger K. , Carcao M. , de Kleijn P. , Silva M. , Hilliard P. , Doria A. , Srivastava A. , Blanchette V. ,   the participants of the International Symposium on Outcome Measures in Hemophilic Arthropathy
Published: September 2016

Introduction

The implementation of early long‐term, regular clotting factor concentrate (CFC) replacement therapy (‘prophylaxis’) has made it possible to offer boys with haemophilia a near normal life. Many different regimens have reported favourable results, but the optimum treatment regimens have not been established and the cost of prophylaxis is very high. Both for optimizing treatment and reimbursement issues, there is a need to provide objective evidence of both short‐ and long‐term results and benefits of prophylactic regimens.

Aims

This report presents a critical review of outcome measures for use in the assessment of musculoskeletal health in persons with haemophilia according to the International Classification of Functioning, Disability and Health (ICF). This framework considers structural and functional changes, activities and participation in a context of both personal and environmental factors.

Methods

Results were generated by a combination of a critical review of available literature plus expert opinion derived from a two day consensus conference between 48 health care experts from different disciplines involved in haemophilia assessment and care. Outcome tools used in haemophilia were reviewed for reliability and validity in different patient groups and for resources required.

Results and conclusion

Recommendations for choice of outcome tools were made according to the ICF domains, economic setting, and reason for use (clinical or research). The next step will be to identify a ‘core’ set of outcome measures for use in clinical care or studies evaluating treatment.
No Change in Interictal PACAP Levels in Peripheral Blood in Women With Chronic Migraine
Authors: Cernuda‐Morollón Eva , Riesco Nuria , Martínez‐Camblor Pablo , Serrano‐Pertierra Esther , García‐Cabo Carmen , Pascual Julio
Published: September 2016

Objective

To determine total pituitary adenylate cyclase activating polypeptide (PACAP) in peripheral blood as a potential marker of the activation of the parasympathetic arm of the trigemino‐vascular system in chronic migraine (CM) in a case‐control study.

Methods

Women older than 17 and diagnosed as CM were recruited. Healthy women with no headache history and women with episodic migraine (EM) served as control groups. Total PACAP and vasoactive intestinal peptide (VIP) levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack and having taken no symptomatic medication the day before.

Results

We assessed serum samples from 86 women with CM, 32 healthy women, and 35 women with EM. There were no differences in PACAP levels in CM patients (109.8 ± 43.8, 97.4 [32.5–253.1] pg/mL), controls (108.7 ± 43.0, 98.7 [50.7–197.3] pg/mL), or EM patients (98.8 ± 34.3, 94.2 [52.0–190.7] pg/mL). VIP levels were significantly increased (P = .027) in CM as compared to control healthy women (136.0 ± 111.5 pg/mL; 103.1 [20.5–534.0] pg/mL vs 88.6 ± 61.0 pg/mL; 66.0 [21.1–256.1]) and EM patients (103.0 ± 56.7 pg/mL; 103.5 [15.2–263.0] pg/mL). In the range of this study variables such as age, CM duration, the presence of aura, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption or kind of preventative treatment did not significantly influence PACAP or VIP levels.

Conclusion

In contrast to VIP, interictal PACAP level measured in peripheral blood does not seem to be a biomarker reflecting parasympathetic activation in CM.
GATA3 expression in primary vulvar Paget disease: a potential pitfall leading to misdiagnosis of pagetoid urothelial intraepithelial neoplasia
Authors: Morbeck Diogo , Tregnago Aline C , Netto Glauco Baiocchi , Sacomani Carlos , Peresi Patricia M , Osório Cynthia T , Schutz Luciana , Bezerra Stephania M , de Brot Louise , Cunha Isabela W
Published: September 2016

Aims

GATA3 has been reported as a specific urothelial marker among organs in the pelvic region, and has been classified as highly sensitive and specific for urothelial and breast carcinomas. Our aim was to verify GATA3 expression in extramammary Paget disease, and to determine whether it can be use to differentiate primary vulvar Paget disease from pagetoid urothelial intraepithelial neoplasia (PUIN). We also analysed HER2 protein expression and HER2 gene amplification and their roles as prognostic factors in extramammary Paget disease.

Methods and results

We analysed GATA3 and HER2 expression in 11 primary vulvar Paget disease cases and two PUIN cases. All cases showed nuclear expression of GATA3. Of 13 cases, five were equivocal for HER2 expression (score 2+) and one was positive (3+). Fluorescence in‐situ hybridization results showed amplification in two of these six cases. Both HER2‐amplified cases were invasive.

Conclusion

GATA3 was positive in all extramammary Paget disease cases tested (13 cases), and it has no value for differentiating between primary and secondary vulvar Paget disease from the urological tract. HER2 amplification might confer an aggressive and invasive pattern in primary vulvar Paget disease, as both amplified cases showed an invasive pattern.