bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Cost Effectiveness of Enhanced Oral Healthcare in Stroke Care Settings (SOCLE II): A Pilot, Stepped Wedge, Cluster Randomized, Controlled Trial Protocol
Authors: Brady Marian C. , Stott David , Weir Christopher J. , Chalmers Campbell , Sweeney Petrina , Donaldson Cam , Barr John , Barr Marion , Pollock Alex , McGowan Sheena , Bowers Naomi , Langhorne Peter
Published: June 2015

Rationale

Stroke-associated pneumonia, a leading cause of hospital-acquired infection after stroke, affects a fifth of stroke survivors annually. Associated with increased risk of death and poorer rehabilitation outcomes, research suggests a possible relationship between stroke-associated pneumonia and patients' oral health.

Aim

The aim of this study is to evaluate the feasibility of a randomized controlled trial of the clinical and cost effectiveness of enhanced oral healthcare vs. usual oral healthcare for people in stroke care settings.

Design

Our pilot, multicentered, pragmatic, stepped wedge, cluster randomized controlled trial oral healthcare [Stroke Oral healthCare pLan Evaluation (SOCLE II)] will compare enhanced oral healthcare intervention and usual oral healthcare. Over 13 months, across 4 wards, we seek to recruit 400 patients (estimating an average of 23 beds per site and a 50% recruitment rate) and 60 nursing staff (estimating an average of 20 members of staff per site and a 75% recruitment rate). Initially, control data (usual oral healthcare) will be collected from all sites. In a randomized, stepped manner, wards will convert to deliver the enhanced oral healthcare intervention.

Study outcome(s)

Outcomes will be captured across dimensions of care (as recommended for evaluations of complex interventions) at baseline and weekly thereafter. Primary outcomes are pneumonia (patients), knowledge and attitudes (staff), and specialist dental referrals (service). Secondary outcomes include oral health quality of life, plaque, antibiotics, length of stay, death (patients), use of oral healthcare equipment and products, completed assessments, and documented oral healthcare plans (staff).

Discussion

As one of the first stepped wedge, cluster randomized, controlled trials in stroke care mapping of the complex intervention, our choice of primary and secondary outcomes and choice of trial design are described.
Safety and Efficacy of Intensive vs. Guideline Antiplatelet Therapy in High-Risk Patients with Recent Ischemic Stroke or Transient Ischemic Attack: Rationale and Design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) Trial (ISRCTN47823388)
Authors:   The TARDIS Trial Investigators
Published: June 2015

Rationale

The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event.

Hypothesis

Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective.

Sample size estimates

The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance.

Methods and design

Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation.

Study outcome

The primary outcome is stroke recurrence and its severity (‘ordinal recurrence’ based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events).

Discussion

The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One-third of patients presented with a transient ischemic attack.
Demographic Trends in Ukraine: Past, Present, and Future
Authors: Romaniuk Anatole , Gladun Oleksandr
Published: June 2015

Ukraine, during the first half of the twentieth century, underwent a series of man‐made demographic catastrophes—World War I, the Bolshevik Revolution, the 1932/33 famine linked to land collectivization, the massive deportations and executions of Stalin's Great Terror, and World War II. This article assembles estimates of the demographic impact of these deadly events. In their absence, it is estimated that Ukraine's hypothetical population would have been 87 million on the eve of independence in 1991, instead of its actual 52 million. Pre‐independence demographic losses were episodic and driven by external forces. By contrast, since independence in 1991, Ukraine has experienced a sustained demographic crisis of its own making. Ukraine's population declined from 52 million in 1990 to 45 million by 2013. Fertility, while it has recovered from its lowest point, remains at a TFR of about 1.5—far below replacement. Emigration, although the greatest hemorrhage of young people in the 1990s is over, is still of concern. The loss of Crimea and the unsettled state of affairs in Southeastern Ukraine give further cause for concern.
Learning on the Job? EU Enlargement and the Assignment of (Shadow) Rapporteurships in the European Parliament
Authors: Hurka Steffen , Kaeding Michael , Obholzer Lukas
Published: June 2015

This article investigates the determinants of assignments to European Parliament negotiating teams comprising both rapporteurs and shadow rapporteurs. We re‐examine the argument that under‐representation of MEPs (Members of the European Parliament) from new Member States on these key posts after enlargement might have been due to a 'learning phase'. We find that MEPs from newer Member States remain considerably less likely to act as rapporteurs during the second term after enlargement (2009–14). Most importantly, this trend also holds for shadow rapporteurships under the co‐decision procedure, which is when they matter most. This structural under‐representation entails important implications for European integration, most importantly that MEPs from newer Member States are less able to influence legislation. We suggest that the patterns we find could be the result of reduced willingness, a more limited skill set, or a structural disadvantage of MEPs from the accession states in the report allocation process.
Context‐dependent effects of yolk androgens on nestling growth and immune function in a multibrooded passerine
Authors: Muriel J. , Salmón P. , Nunez‐Buiza A. , de Salas F. , Pérez‐Rodríguez L. , Puerta M. , Gil D.
Published: June 2015

Female birds may adjust their offspring phenotype to the specific requirements of the environment by differential allocation of physiologically active substances into yolks, such as androgens. Yolk androgens have been shown to accelerate embryonic development, growth rate and competitive ability of nestlings, but they can also entail immunological costs. The balance between costs and benefits of androgen allocation is expected to depend on nestling environment. We tested this hypothesis in a multibrooded passerine, the spotless starling,Sturnus unicolor. We experimentally manipulated yolk androgen levels using a between‐brood design and evaluated its effects on nestling development, survival and immune function. Both in first and replacement broods, the embryonic development period was shorter for androgen‐treated chicks than controls, but there were no differences in second broods. In replacement broods, androgen‐treated chicks were heavier and larger than those hatched from control eggs, but this effect was not observed in the other breeding attempts. Androgen exposure reduced survival with respect to controls only in second broods. Regarding immune function, we detected nonsignificant trends for androgen treatment to activate two important components of innate and adaptive immunity (IL‐6 and Ig‐A levels, respectively). Similarly, androgen‐treated chicks showed greater lymphocyte proliferation than controls in the first brood and an opposite trend in the second brood. Our results indicate that yolk androgen effects on nestling development and immunity depend on the environmental conditions of each breeding attempt. Variation in maternal androgen allocation to eggs could be explained as the result of context‐dependent optimal strategies to maximize offspring fitness.
Is geographic variation within species related to macroevolutionary patterns between species?
Authors: Fisher‐Reid M. C. , Wiens J. J.
Published: June 2015

The relationship between microevolution and macroevolution is a central topic in evolutionary biology. An aspect of this relationship that remains very poorly studied in modern evolutionary biology is the relationship between within‐species geographic variation and among‐species patterns of trait variation. Here, we tested the relationship between climate and morphology among and within species in the salamander genus Plethodon. We focus on a discrete colour polymorphism (presence and absence of a red dorsal stripe) that appears to be related to climatic distributions in a common, wide‐ranging species (Plethodon cinereus). We find that this trait has been variable among (and possibly within) species for >40 million years. Furthermore, we find a strong relationship among species between climatic variation and within‐species morph frequencies. These between‐species patterns are similar (but not identical) to those in the broadly distributed Plethodon cinereus. Surprisingly, there are no significant climate–morphology relationships within most other polymorphic species, despite the strong between‐species patterns. Overall, our study provides an initial exploration of how within‐species geographic variation and large‐scale macroevolutionary patterns of trait variation may be related.
Pike Esox lucius as an emerging model organism for studies in ecology and evolutionary biology: a review
Authors: Forsman A. , Tibblin P. , Berggren H. , Nordahl O. , Koch‐Schmidt P. , Larsson P.
Published: June 2015

The pike Esox lucius is a large, long‐lived, iteroparous, top‐ predator fish species with a circumpolar distribution that occupies a broad range of aquatic environments. This study reports on a literature search and demonstrates that the publication rate of E. lucius research increases both in absolute terms and relative to total scientific output, and that the focus of investigation has changed over time from being dominated by studies on physiology and disease to being gradually replaced by studies on ecology and evolution. Esox lucius can be exploited as a model in future research for identifying causes and consequences of phenotypic and genetic variation at the levels of individuals, populations and species as well as for investigating community processes.
Expression of plzfa in embryo and adult of medaka Oryzias latipes
Authors: Zhao H. B. , Zhang X. Y. , Feng G. Q. , Guo M. M. , Chang P. , Qi C. , Zhong X. P. , Zhou Q. C. , Wang J. L.
Published: June 2015

In this study, a homologous gene named plzfa was identified and characterized in medaka Oryzias latipes. Oryzias latipes plzfa was detected in all the tissues including brain, gill, muscle, liver, intestine, kidney, spleen, testis and ovary using reverse transcriptase (RT)‐PCR. plzfa was detected in the oocytes of the ovary and in the spermatogonia and somitic cells of the testis by in situ hybridization. plzfa had a maternal origin with continuous and dynamic expression during embryonic development. plzfa was observed in the brain, neural rod and sensor organs including the eyes, ears and nose during embryogenesis. plzfa was also detected in the neural crest, somite, pectoral fin, intestine and skin. These results indicate that plzfa is a pleiotropic gene that may play major roles in various tissues.
The deubiquitinating enzyme USP46 regulates AMPA receptor ubiquitination and trafficking
Authors: Huo Yuda , Khatri Natasha , Hou Qingming , Gilbert James , Wang Guan , Man Heng‐Ye
Published: June 2015

Alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPARs) are the primary mediators for inter‐neuronal communication and play a crucial role in higher brain functions including learning and memory. Our previous work demonstrated that AMPARs are subject to ubiquitination by the E3 ligase Nedd4, resulting in EPS15‐mediated receptor internalization and Ubiquitin (Ub)–proteasome pathway (UPP)‐dependent degradation. Protein ubiquitination is a highly dynamic and reversible process, achieved via the balance between ubiquitination and deubiquitination. However, deubiquitination of mammalian AMPARs and the responsible deubiquitinating enzymes remain elusive. In this study, we identify USP46 as the deubiquitinating enzyme for AMPARs. We find that AMPARs are subject to K63 type ubiquitination, and USP46 is able to deubiquitinate AMPARs in vivo and in vitro. In heterologous cells and neurons, expression of USP46 results in a significant reduction in AMPAR ubiquitination, accompanied by a reduced rate in AMPAR degradation and an increase in surface AMPAR accumulation. By contrast, knockdown of USP46 by RNAi leads to elevated AMPAR ubiquitination and a reduction in surface AMPARs at synapses in neurons. Consistently, miniature excitatory postsynaptic currents recordings show reduced synaptic strength in neurons expressing USP46‐selective RNAi. These results demonstrate USP46‐mediated regulation of AMPAR ubiquitination and turnover, which may play an important role in synaptic plasticity and brain function.

image

Protein ubiquitination is a highly dynamic and reversible process, achieved via the balance between ubiquitination and deubiquitination. The glutamatergic AMPARs, which mediate most of the excitatory synaptic transmission in the brain, are known to be subjected to Nedd4‐mediated ubiquitination; however, the deubiquitination process and the responsible deubiquitinating enzymes (DUBs) for mammalian AMPARs remain elusive. We find that AMPARs are subject to K63‐type ubiquitination, and identify USP46 as the DUB for AMPARs. USP46 deubiquitinates AMPARs in vitro and in vivo. Up‐ or down‐regulation of USP46 leads to changes in AMPAR ubiquitination, surface expression, and trafficking, as well as the strength of synaptic transmission. USP46‐mediated regulation of AMPAR ubiquitination and turnover may play an important role in synaptic plasticity and brain function.
Interventional Management of Unprotected Left Main Coronary Artery Disease: Patient Selection and Technique Optimization
Authors: Rizik David G. , Klassen Kevin J. , Burke Robert F. , Hodgson John McB. , Stone Gregg W.
Published: June 2015

For many years, coronary artery bypass graft surgery has been the gold standard for revascularization of patients with left main disease; however, increasing evidence suggests that percutaneous coronary intervention with drug‐eluting stents may be an acceptable alternative or even preferred in select cases. This review will present clinical evidence examining the outcomes of drug‐eluting stents compared to coronary artery bypass graft surgery for unprotected left main coronary artery disease and discuss the anatomic factors, patient variables, and clinical strategies that may dictate choice of revascularization modality for patients with left main disease. If percutaneous coronary intervention is selected to treat unprotected left main disease, meticulous technique is essential to optimize outcomes, including use of procedural physiology and imaging guidance, optimal stent and adjunct pharmacology use, and expert management of the distal bifurcation. Finally, issues of equipoise and uncertainty are identified, representing areas for future investigation.
Longitudinal changes in dental services provided by Australian dentists
Authors: Ju Xiangqun , Brennan David S. , Spencer A. John , Teusner Dana N.
Published: June 2015

Objective

To estimate the longitudinal change in number of patients per year (PPY) per dentist by age and sex of dentists in Australia.

Method

Dentists were selected randomly from Australian dental registers, the baseline collection was in 1983 and repeated approximately every 5 years until 2009. Dentist's practice activity was collected by mailed questionnaire. Number of PPY was calculated from work hours and number of patients per week per dentist. Mixed‐effects regression was applied to estimate both individual random effects and population averaged fixed effects for the number of PPY provided by age, time, and sex.

Results

A total of 1,449 dentists completed 2,822 questionnaires from six waves of data collection (1983 to 2010). The average PPY decreased over the time of the study. The rate of change in PPY accelerated during younger ages and reached a peak when they moved into 50 years old (B = 86.04, P < 0.0001), and then decelerated (B = −0.90, P = 0.0002) across time. The mean number of PPY was higher in male dentists than female dentists in the same 10‐year age group. The pattern of PPY change with aging was an inverted U‐shape for male dentists. In contrast, there was a U‐shape for female dentists.

Conclusions

The longitudinal change in PPY with aging was an inverted U‐shape, which accelerated during younger age, and decelerated after reaching a peak at 50 years old. Males had higher PPY than female dentists at the same age. The pattern of PPY was different between male and female dentists.
Galloyl benzamide-based compounds modulating tumour necrosis factor α-stimulated c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signalling pathways
Authors: Leo Valentina , Stefanachi Angela , Nacci Carmela , Leonetti Francesco , de Candia Modesto , Carotti Angelo , Altomare Cosimo D , Montagnani Monica , Cellamare Saverio
Published: June 2015

Objectives

The aim of this work is to investigate whether and how two newly synthesized 3,4,5-trimethoxygalloyl-containing compounds 1 and 3 interfere with the mitogen-activated protein kinase (MAPK) signalling pathways involved in several pathological events, ranging from inflammatory diseases to cancer.

Methods

The effects on the phosphorylation of MAP kinases (c-Jun N-terminal kinases (JNKs), p38) and activation of nuclear factor-kappa B (NF-κB) pathways of 1 and its 1H-indazole-containing analogue 3, compared with those elicited by the known Adenosine Triphosphate (ATP)-competitive JNK inhibitor SP600125, were evaluated through Western blot analysis in murine fibroblasts NIH-3T3 and human endothelial cells EA.hy926 acutely treated with tumour necrosis factor-α (TNF-α). Their effects on cell viability were also assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay.

Key findings

In cultured murine fibroblasts, 1 inhibited JNK signalling with a different mechanism from SP600125. It reduced c-Jun phosphorylation without altering phosphorylation levels of JNK protein. Compound 3, showing a profile similar to SP600125, inhibited JNK phosphorylation and partially inhibited p38 MAPK at 50 μm concentration. Compound 3 and SP600125 showed similar behaviour in both cell cultures. In contrast, compound 1 in EA.hy926 cells significantly interfered with JNK phosphorylation, did not decrease phosphorylation of c-Jun (Ser73), whereas significantly suppressed phosphorylation of p38 MAPK and reversed degradation of NF-κB signalling components.

Conclusions

3,4,5-Trimethoxygalloyl-based compounds 1 and 3, which did not show significant cell toxicity, modulate the TNF-α-induced activation of MAPK signalling, mainly inhibiting phosphorylation of JNK, c-Jun and p38 MAPK, in murine fibroblasts and human endothelial cells with different MAPK selectivity profiles. These compounds deserve future investigation in specific cell-based disease models and in-vivo pharmacology.
1118-20, an indazole diarylurea compound, inhibits hepatocellular carcinoma HepG2 proliferation and tumour angiogenesis involving Wnt/β-catenin pathway and receptor tyrosine kinases
Authors: Lu Yu-Yin , Wang Jing-Jing , Zhang Xin-Ke , Li Wen-Bao , Guo Xiu-Li
Published: June 2015

Objectives

Sorafenib is a first multi-kinase inhibitor and one of the most widely used small-molecule oral-targeted drugs. It has been widely used for the treatment of patients with advanced renal cell carcinoma and hepatocellular carcinoma. However, some common adverse effects of sorafenib may impact quality of life. In this study, we evaluated the inhibitory effect on the growth of hepatocellular carcinoma cell line (HepG2) and suppression on angiogenesis of 1118-20, a newly synthesized indazole diarylurea compound.

Methods

We evaluated the activity of 1118-20 against HepG2 cells growth and tumour angiogenesis of human umbilical vascular endothelial cell line (HUVECs) with sorafenib as a positive control.

Key findings

The cytotoxic efficacy of 1118-20 was higher in HepG2 cells than human normal liver cell line (HL-7702). 1118-20 significantly suppressed the proliferation of HepG2 cells by apoptosis induction via Bcl-2 family-mediated mitochondria pathway and inhibition on Wnt/β-catenin signalling pathway. 1118-20 effectively blunt the motility and migration, and inhibited the formation of capillary tube of HUVECs through suppression of angiogenic factors expression. Moreover, the results indicated that 1118-20 exerted higher efficacy than sorafenib on tumour cell proliferation and angiogenesis.

Conclusions

Compared with its parent drug sorafenib, we found that 1118-20 possessed more potential on inhibition of angiogenesis and cancer cells growth. Inhibitory effect of 1118-20 on non-tumour liver cell HL-7702 was lower than that on hepatoma carcinoma cell HepG2. These results suggest that 1118-20 is a promising candidate compound that could be developed to a potent anticancer agent.
The use of water-soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle-invasive bladder cancer
Authors: Chatta Dani , Cottrell Lewis , Burnett Bruce , Laverty Garry , McConville Christopher
Published: June 2015

Objectives

To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine.

Methods

Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine.

Key findings

Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine.

Conclusion

The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer.
Immune system transcriptome in gingival tissues of young nonhuman primates
Authors: Gonzalez O. A. , Nagarajan R. , Novak M. J. , Orraca L. , Gonzalez‐Martinez J. A. , Kirakodu S. S. , Ebersole J. L.
Published: June 2015

Background and Objective

Young/adolescent humans harbor many microorganisms associated with periodontal disease in adults and show substantial gingival inflammatory responses. However, younger individuals do not demonstrate the soft‐ and hard‐tissue destruction that hallmark periodontitis.

Material and Methods

This study evaluated responses to the oral microbial ecology in gingival tissues from clinically healthy young Macaca mulatta (< 3 years of age) compared with older animals (5–23 years of age). RNA was isolated from the tissues and analyzed for the transcriptome using the Rhesus Macaque GeneChip (Affymetrix).

Results

Global transcriptional profiling of four age groups revealed a subset of 159 genes that were differentially expressed across at least one of the age comparisons. Correlation metrics generated a relevance network abstraction of these genes. Partitioning of the relevance network revealed seven distinct communities comprising functionally related genes associated with host inflammatory and immune responses. A group of genes was identified that were selectively increased/decreased or positively/negatively correlated with gingival profiles in the animals. A principal components analysis created metagenes of expression profiles for classifying the 23 animals.

Conclusion

The results provide novel system‐level insights into gene‐expression differences in gingival tissues from healthy young animals, weighted toward host responses associated with anti‐inflammatory biomolecules or those linked with T‐cell regulation of responses. The combination of the regulated microenvironment may help to explain the apparent ‘resistance’ of younger individuals to developing periodontal disease.
Parents' experiences, needs, and preferences in pediatric diabetes care: Suggestions for improvement of care and the possible role of the Internet. A qualitative study
Authors: Boogerd Emiel A. , Maas‐van Schaaijk Nienke M. , Noordam Cees , Marks Hans J. G. , Verhaak Chris M.
Published: June 2015

Purpose

To investigate the needs and preferences of parents of children with type 1 diabetes (T1D) concerning pediatric diabetes care and use of Internet in care.

Design and Methods

Parents of 34 children, aged 2–12, with T1D participated in seven focus group interviews.

Results

Analysis revealed provision of tailored care, disease information, peer support, and accessibility of healthcare professionals as major needs in parents. Internet could be used to satisfy these needs.

Practical Implications

According to parents, diabetes teams should focus on the impact of the disease, parents' experience, and the child's development, and provide online professional and peer support.
The Economics of Disaster Relief
Authors: Dari‐Mattiacci Giuseppe , Faure Michael G.
Published: June 2015

We distinguish among three types of actions that can be taken to alleviate the consequences of natural disasters: precautionary efforts (made ex ante), relief efforts (made in the immediate aftermath of a disaster), and recovery efforts (made ex post). We argue that recognizing this distinction lessens many of the problems that the literature attributes to government intervention and hence expands the scope of government action following disasters. Relief is less likely than recovery to generate over‐supply by the government and over‐reliance by victims.
Deciphering the metabolic response of Mycobacterium tuberculosis to nitrogen stress
Authors: Williams Kerstin J. , Jenkins Victoria A. , Barton Geraint R. , Bryant William A. , Krishnan Nitya , Robertson Brian D.
Published: June 2015

A key component to the success of Mycobacterium tuberculosis as a pathogen is the ability to sense and adapt metabolically to the diverse range of conditions encountered in vivo, such as oxygen tension, environmental pH and nutrient availability. Although nitrogen is an essential nutrient for every organism, little is known about the genes and pathways responsible for nitrogen assimilation in M. tuberculosis. In this study we have used transcriptomics and chromatin immunoprecipitation and high‐throughput sequencing to address this. In response to nitrogen starvation, a total of 185 genes were significantly differentially expressed (96 up‐regulated and 89 down regulated; 5% genome) highlighting several significant areas of metabolic change during nitrogen limitation such as nitrate/nitrite metabolism, aspartate metabolism and changes in cell wall biosynthesis. We identify GlnR as a regulator involved in the nitrogen response, controlling the expression of at least 33 genes in response to nitrogen limitation. We identify a consensus GlnR binding site and relate its location to known transcriptional start sites. We also show that the GlnR response regulator plays a very different role in M. tuberculosis to that in non‐pathogenic mycobacteria, controlling genes involved in nitric oxide detoxification and intracellular survival instead of genes involved in nitrogen scavenging.
BIOSOCIAL INHERITANCE: A FRAMEWORK FOR THE STUDY OF THE INTERGENERATIONAL TRANSMISSION OF HEALTH DISPARITIES
Authors: Hoke Morgan K. , McDade Thomas
Published: June 2015

Proponents of global market expansion claim that economic growth brings prosperity and creates a more equitable global society, yet these efforts may result in the exacerbation of economic disparities that translates into significant disparities in health. These trends underscore the importance of research examining the social determinants of health in an increasingly unequal world. This article brings together concepts from biocultural anthropology, developmental origins of health and disease, and research examining the long‐term effects of early environments on social capital to formulate the notion of biosocial inheritance. Biosocial inheritance is the process whereby social adversity in one generation is transmitted to the next through reinforcing biological and social mechanisms that impair health, exacerbating social and health disparities. Such a theoretical framework considers contemporary and historic political‐economic forces that shape inequalities in human health, across generations. We examine the biosocial determinants of growth in the Andes as a case study of biosocial inheritance, developing a model that will illuminate the contemporary and historic sources of persistent poverty in low‐income communities around the world. By highlighting the biosocial mechanisms underpinning the intergenerational transmission of poverty, this model allows for the formulation of interventions aimed at breaking the cycle of poverty and a reconsideration of the way we think about poverty and social mobility.
A WORLD OF SUFFERING? BIOCULTURAL APPROACHES TO FAT STIGMA IN THE GLOBAL CONTEXTS OF THE OBESITY EPIDEMIC
Authors: Brewis Alexandra A. , Wutich Amber
Published: June 2015

Even as obesity rates rise, weight‐related stigma remains widespread in the United States and leads to many documented social, economic, and health disparities. These include lower wages, less academic achievement, social exclusion as early as childhood, psychosocial stress, depression, and additional weight gain. Recent research documents the proliferation of antifat beliefs across the globe, but we know little about how this fat stigma varies across cultures. A clearer empirical and theoretical understanding of fat stigma in cultural context is essential to gauging its likely biocultural impacts across populations. Using data from Paraguay, Bolivia, India, and students and Muslim women in the United States (N = 414 women), we show that psychometric scales suggest high levels of stated or expressed fat stigma in all these samples, capturing globalizing anti‐fat norms. However, when we assess what people think implicitly through reaction‐time implicit association tests, we find marked variation across sites in the degree to which people are internalizing these stigmatized ideas around obesity. In India and among U.S. university students, women tend to internalize the idea of “fat” negatively. Paraguay women present, on average, fat‐neutral internalized views. In Bolivia and among Muslim women in the United States, average assessments suggest fat‐positive internalized views. This indicates fat stigmatizing norms are not always internalized, even as explicit fat stigma otherwise appears to be globalizing. Our findings indicate that the proposed biocultural relationships between fat stigma and health disparities may be complex and very context specific.
How do cold‐sensitive species endure ice ages? Phylogeographic and paleodistribution models of postglacial range expansion of the mesothermic drought‐tolerant coniferAustrocedrus chilensis
Authors: Souto Cintia P. , Kitzberger Thomas , Arbetman Marina P. , Premoli Andrea C.
Published: June 2015

In view of global climate change, it is important to understand the responses of tree species to climate changes in the past. Combinations of phylogeographic analysis of genetic evidence, coupled with species distribution models (SDMs), are improving our understanding on this subject.

We combinedSDMs and microsatellite data from populations of the entire range ofAustrocedrus chilensis, a dominant mesotherm (cold‐sensitive) conifer of dryland forests of the southern Andes, to test the hypothesis of long‐distance postglacial migration from northern and warmer refugia at the Last Glacial Maximum (LGM).

TheSDMindicated suitable conditions forAustrocedrusin northern Chile (western) at theLGMand largely unsuitable conditions in Argentina (eastern). Population genetic diversity and effective population sizes within populations decreased southward along the Andes, consistent with the hypothesis of long‐distance dispersal from a northern refugium.

Results support the hypothesis of one (or a few) warmer (low latitude) refugia in Chile forAustrocedrus. On balance, the evidence suggests that in contrast to cold‐tolerant tree taxa with the capacity to fast‐track postglacial warming thanks to local refugia, cold‐sensitive species might have undergone long‐distance range expansion, lagging behind progressive climate change throughout the Holocene.
Evolution of dispersal in a multi‐trophic community context
Authors: Amarasekare Priyanga
Published: June 2015

Much is known about the evolution of dispersal when species interact with their resources or natural enemies, but very little is known about dispersal evolution when species interact with both resources and natural enemies. Here I investigate how the dispersal of an intermediate consumer evolves in response to its interactions with a basal resource and top predator. I find that dispersal evolution is possible even when the consumer species is not directly affected by environmental variability, but rather experiences the consequences that such variability has on its resource and predator. Spatial variation in the consumer's fitness is driven by spatial heterogeneity in resource productivity, which determines whether a predator can colonize a resource‐consumer community. Temporal variation in the consumer's fitness is driven by random disturbances that cause periodic local extinctions of the predator, followed by recolonizations that lead to transient fluctuations in consumer abundance. When spatial variation in resource productivity is low and the predator can colonize all patches in the landscape, there is no spatial variation in consumer fitness but temporal variation in fitness favors the evolution of a dispersal monomorphism. When spatial variation in resource productivity is high and the predator cannot colonize many patches in the landscape, spatial variation in fitness selects against dispersal. In this case, temporal variation can promote the evolution of a dispersal polymorphism with sedentary and mobile phenotypes, but only for certain types of tri‐trophic interactions. This finding underscores the importance of indirect interactions in shaping the evolution of dispersal. While the ecological community can provide a strong selective environment for the evolution of dispersal, the nature of interactions between trophic levels can also impose constraints on evolution.
THE VALIDITY OF SUBJECTIVE PERFORMANCE MEASURES: SCHOOL PRINCIPALS IN TEXAS AND DENMARK
Authors: MEIER KENNETH J. , WINTER SØREN C. , O'TOOLE LAURENCE J. , FAVERO NATHAN , ANDERSEN SIMON CALMAR
Published: June 2015

Public management studies are increasingly using survey data on managers' perceptions of performance to measure organizational performance. These perceptual measures are tempting to apply because archival performance data or surveys of target group outcomes and satisfaction are often lacking, costly to provide, and are highly policy specific rendering generalization difficult. But are perceptual performance measures valid, and do they generate unbiased findings? We examine these questions in a comparative study of middle managers in schools in Texas and Denmark. The findings are remarkably similar. Managers systematically overestimate the performance of their organization, perceptual performance is only weakly associated with archival performance, and managers do not provide sophisticated assessment of performance by giving their organization credit for the constraints it meets or discounting the resources it has. Even worse, the use of perceptual performance measures seems to provide biased estimates when examining how management affects performance. This is due to both random measurement error and common source bias.
Identification of low Ca2+ stress‐induced embryo apoptosis response genes in Arachis hypogaea by SSH‐associated library lift (SSHaLL)
Authors: Chen Hua , Zhang Chong , Cai Tie cheng , Deng Ye , Zhou Shuangbiao , Zheng Yixiong , Ma Shiwei , Tang Ronghua , Varshney Rajeev K. , Zhuang Weijian
Published: June 2015

Calcium is a universal signal in the regulation of wide aspects in biology, but few are known about the function of calcium in the control of early embryo development. Ca2+ deficiency in soil induces early embryo abortion in peanut, producing empty pods, which is a general problem; however, the underlying mechanism remains unclear. In this study, embryo abortion was characterized to be caused by apoptosis marked with cell wall degradation. Using a method of SSH cDNA libraries associated with library lift (SSHaLL), 62 differentially expressed genes were isolated from young peanut embryos. These genes were classified to be stress responses, catabolic process, carbohydrate and lipid metabolism, embryo morphogenesis, regulation, etc. The cell retardation with cell wall degradation was caused by up‐regulated cell wall hydrolases and down‐regulated cellular synthases genes. HsfA4a, which was characterized to be important to embryo development, was significantly down‐regulated under Ca2+‐deficient conditions from 15 days after pegging (DAP) to 30 DAP. Two AhCYP707A4 genes, encoding abscisic acid (ABA) 8′‐hydroxylases, key enzymes for ABA catabolism, were up‐regulated by 21‐fold under Ca2+‐deficient conditions upstream of HsfA4a, reducing the ABA level in early embryos. Over‐expression of AhCYP707A4 in Nicotiana benthamiana showed a phenotype of low ABA content with high numbers of aborted embryos, small pods and less seeds, which confirms that AhCYP707A4 is a key player in regulation of Ca2+ deficiency‐induced embryo abortion via ABA‐mediated apoptosis. The results elucidated the mechanism of low Ca2+‐induced embryo abortion and described the method for other fields of study.
DNA barcoding: an efficient tool to overcome authentication challenges in the herbal market
Authors: Mishra Priyanka , Kumar Amit , Nagireddy Akshitha , Mani Daya N. , Shukla Ashutosh K. , Tiwari Rakesh , Sundaresan Velusamy
Published: June 2015

The past couple of decades have witnessed global resurgence of herbal‐based health care. As a result, the trade of raw drugs has surged globally. Accurate and fast scientific identification of the plant(s) is the key to success for the herbal drug industry. The conventional approach is to engage an expert taxonomist, who uses a mix of traditional and modern techniques for precise plant identification. However, for bulk identification at industrial scale, the process is protracted and time‐consuming. DNA barcoding, on the other hand, offers an alternative and feasible taxonomic tool box for rapid and robust species identification. For the success of DNA barcode, the barcode loci must have sufficient information to differentiate unambiguously between closely related plant species and discover new cryptic species. For herbal plant identification, matK, rbcL, trnH‐psbA, ITS, trnL‐F, 5S‐rRNA and 18S‐rRNA have been used as successful DNA barcodes. Emerging advances in DNA barcoding coupled with next‐generation sequencing and high‐resolution melting curve analysis have paved the way for successful species‐level resolution recovered from finished herbal products. Further, development of multilocus strategy and its application has provided new vistas to the DNA barcode‐based plant identification for herbal drug industry. For successful and acceptable identification of herbal ingredients and a holistic quality control of the drug, DNA barcoding needs to work harmoniously with other components of the systems biology approach. We suggest that for effectively resolving authentication challenges associated with the herbal market, DNA barcoding must be used in conjunction with metabolomics along with need‐based transcriptomics and proteomics.
Adenylate cyclase 5is required for melanophore and male pattern development in the guppy (Poecilia reticulata)
Authors: Kottler Verena A. , Künstner Axel , Koch Iris , Flötenmeyer Matthias , Langenecker Tobias , Hoffmann Margarete , Sharma Eshita , Weigel Detlef , Dreyer Christine
Published: June 2015

Guppies (Poecilia reticulata) are colorful fish that have attracted the attention of pigmentation researchers for almost a century. Here, we report that the blond phenotype of the guppy is caused by a spontaneous mutation in the guppy ortholog ofadenylate cyclase 5(adcy5). Using double digest restriction site‐associatedDNAsequencing (ddRADseq) and quantitative trait locus (QTL) mapping, we linked the blond phenotype to a candidate region of 118 kb, in which we subsequently identified a 2‐bp deletion inadcy5that alters splicing and leads to a premature stop codon. We show thatadcy5, which affects life span and melanoma growth in mouse, is required for melanophore development and formation of male orange pigmentation traits in the guppy. We find that some components of the male orange pattern are particularly sensitive to loss of Adcy5 function. Our work thus reveals a function for Adcy5 in patterning of fish color ornaments.
Rules and the Doctrine of Performance Management
Authors: Jakobsen Mads L. F. , Mortensen Peter B.
Published: June 2015

The doctrine of performance management has been promoted as an alternative to rule‐based governance. Analyzing performance management as a system of rules, this article examines how performance management is adopted through rules. The question is examined based on a systematic counting and content coding of national rules within the domain of primary education in Denmark from 1989 to 2010. Contrary to the prescriptions of the performance management doctrine, the analysis shows a clear increase in the number of rules. This reflects the creation of many new rules about performance measurement without a proportionate repeal of production rules constraining the autonomy of public service providers and their managers. The result is congruent with the expectations derived from the literature on rule dynamics, which emphasizes rules as the carriers of learning and interests. The article thereby demonstrates the utility of analyzing performance management as a system of rules.
Traces of Henry Wotton in continental Alba Amicorum
Authors: Schlueter June , Dubischar Markus
Published: June 2015

Surviving copies of alba amicorum, or friendship albums, a genre that flourished in Protestant regions of the Continent, contain details concerning the lives of their early modern owners and contributors. While the fashion of owning an album did not generally extend to England, Henry Wotton, an Englishman who spent much of his career on the Continent, was a frequent contributor to others's albums. This article examines ten of Wotton's holographic entries, inscribed between 1590 and 1627, that provide insight into the biography and character of the poet‐diplomat who served King James as ambassador to Venice and Provost of Eton.
A QMRA for the Transmission of ESBL‐Producing Escherichia coli and Campylobacter from Poultry Farms to Humans Through Flies
Authors: Evers Eric G. , Blaak Hetty , Hamidjaja Raditijo A. , de Jonge Rob , Schets Franciska M.
Published: June 2015

The public health significance of transmission of ESBL‐producing Escherichia coli and Campylobacter from poultry farms to humans through flies was investigated using a worst‐case risk model. Human exposure was modeled by the fraction of contaminated flies, the number of specific bacteria per fly, the number of flies leaving the poultry farm, and the number of positive poultry houses in the Netherlands. Simplified risk calculations for transmission through consumption of chicken fillet were used for comparison, in terms of the number of human exposures, the total human exposure, and, for Campylobacter only, the number of human cases of illness. Comparing estimates of the worst‐case risk of transmission through flies with estimates of the real risk of chicken fillet consumption, the number of human exposures to ESBL‐producing E. coli was higher for chicken fillet as compared with flies, but the total level of exposure was higher for flies. For Campylobacter, risk values were nearly consistently higher for transmission through flies than for chicken fillet consumption. This indicates that the public health risk of transmission of both ESBL‐producing E. coli and Campylobacter to humans through flies might be of importance. It justifies further modeling of transmission through flies for which additional data (fly emigration, human exposure) are required. Similar analyses of other environmental transmission routes from poultry farms are suggested to precede further investigations into flies.
A pilot study of the efficacy of wipes containing chlorhexidine 0.3%, climbazole 0.5% and Tris‐EDTA to reduce Malassezia pachydermatis populations on canine skin
Authors: Cavana Paola , Peano Andrea , Petit Jean‐Yanique , Tizzani Paolo , Perrot Sébastien , Bensignor Emmanuel , Guillot Jacques
Published: June 2015

Background

Wipes containing chlorhexidine and azole derivates have been recommended for veterinary use. No study has been published about their activity against Malassezia pachydermatis.

Hypothesis/Objectives

To evaluate the in vivo and in vitro activity of wipes soaked in a chlorhexidine, climbazole and Tris‐EDTA solution against Malassezia pachydermatis.

Animals

Five research colony shar‐pei dogs.

Methods

Wipes were applied once daily onto the left axilla, left groin and perianal area (protocol A), and twice daily on the right axilla, right groin and umbilical region (protocol B) for 3 days. In vivo activity was evaluated by quantifying Malassezia colonies through contact plates on the selected body areas before and after wipe application. The activity of the solution in which the wipes were soaked was assessed in vitro by contact tests following the European Standard UNI EN 1275 guidelines.

Results

Samples collected after wipe application showed a significant and rapid reduction of Malassezia yeast CFU. No significant difference in the Malassezia reduction was found between protocols A and B. In vitro assay showed 100% activity against Malassezia yeasts after a 15 min contact time with the wipe solution.

Conclusions and clinical importance

Wipes containing chlorhexidine, climbazole and Tris‐EDTA substantially reduced the M. pachydermatis population on the skin of dogs. The results, although this was an uncontrolled study performed on a small number of dogs, suggest that these wipes may be useful for topical therapy of Malassezia dermatitis involving the lips, paws, perianal area and skin folds.