bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic size responses to climate change: prevailing effects of rising temperature drive long‐term body size increases in a semi‐arid passerine
Authors: Gardner Janet L. , Amano Tatsuya , Mackey Brendan G. , Sutherland William J. , Clayton Mark , Peters Anne
Published: December 2013

Changes in animal body size have been widely reported as a correlate of contemporary climate change. Body size affects metabolism and fitness, so changing size has implications for resilience, yet the climatic factors that drive size variation remain poorly understood. We test the role of mean and extreme temperature, rainfall, and remotely sensed primary productivity (NDVI) as drivers of body size in a sedentary, semi‐arid Australian passerine, Ptilotula (Lichenostomus) penicillatus, over 23 years. To distinguish effects due to differential growth from changes in population composition, we analysed first‐year birds and adults separately and considered climatic variation at three temporal scales (current, previous, and preceding 5 years). The strongest effects related to temperature: in both age classes, larger size was associated with warmer mean temperatures in the previous year, contrary to Bergmann's Rule. Moreover, adults were larger in warmer breeding seasons, while first years was larger after heatwaves; these effects are more likely to be mediated through size‐dependent mortality, highlighting the role of body size in determining vulnerability to extinction. In addition to temperature, larger adult size was associated with lower primary productivity, which may reflect a trade‐off between vegetative growth and nectar production, on which adults rely. Finally, lower rainfall was associated with decreasing size in first year and adults, most likely related to decreased food availability. Overall, body size increased over 23 years, strongly in first‐year birds (2.7%) compared with adults (1%), with size outcomes a balance between competing drivers. As rainfall declined over time and productivity remained fairly stable, the temporal increase in body size appears largely driven by rising mean temperature and temperature extremes. Body size responses to environmental change are thus complex and dynamic, driven by effects on growth as well as mortality.
Renal nurses’ views of the potential role of pharmacists in outpatient dialysis centres: a qualitative study
Authors: Salgado Teresa M , Moles Rebekah , Benrimoj Shalom I , Fernandez-Llimos Fernando
Published: December 2013

Objectives

The aim of this study was to explore the differences in the views of Australian and Portuguese renal nurses on the provision of clinical pharmacy services in outpatient dialysis centres.

Methods

Semi-structured interviews were conducted with Australian and Portuguese renal nurses. The interviews were recorded and thematically content-analysed.

Key findings

Three main themes were identified: nurses’ opinions towards pharmacists’ current role; nurses’ opinions towards pharmacists’ future role; and future clinical pharmacy services to be provided. While Australian nurses appeared to be aware of pharmacists’ competencies and viewed a role for pharmacists within the team, Portuguese nurses showed low expectations of pharmacists and regarded them as external to the team.

Conclusions

Previous or lack of exposure to pharmacists’ clinical skills and the existence of health policies that promote interprofessional collaboration appear to influence nurses’ views.
Women Stroke Association Statement on Stroke
Authors: Pezzella Francesca Romana , Santalucia Paola , Vadalà Rita , Giugni Elisabetta , Zedde Maria Luisa , Sessa Maria , Anticoli Sabrina , Caso Valeria
Published: December 2013

We describe the current and future objectives of the Women Stroke Association, a nonprofit multidisciplinary organization promoting research awareness on medical, psychological, and social issues concerning women affected by cerebrocardiovascular disease. In this paper, we deal with only cerebrovascular disease, whereas cardiovascular disorders will be addressed in a future paper. Gender differences in the clinical presentation of cerebrovascular diseases have been repeatedly suggested, and some treatment options may not be as effective and safe in men and women. For many years, women have either been underrepresented or excluded from randomized clinical trials, and the majority of therapeutic research has been carried on predominantly male populations. Furthermore, gender differences have been shown to contribute to different responses to cerebrovascular drugs in women when compared with men, regarding pharmacokinetics, pharmacodynamics, and physiology. In this statement, we discuss main research fields relevant to Women Stroke Association's mission and commitment, highlighting opportunities and critical from the women's health perspective. Future directions and goals of the Women Stroke Association arise from these considerations and represent the association's commitment to combating stroke.
Cochrane Stroke Group: Twenty Years of Evidence-Based Stroke Medicine
Authors: Berge E. , Langhorne P.
Published: December 2013

The Cochrane Stroke Group was one of the first specialist review groups set up within The Cochrane Collaboration and has been in existence for 20 years. Its key outputs include a number of high profile reviews in the area of the management of stroke, which have become one of the most important sources of information for clinical practice guidelines. The work of the group is only possible through a collaborative network of staff, editors, and authors.
Incumplimiento de la legislación laboral en Chile
Authors: KANBUR Ravi , RONCONI Lucas , WEDENOJA Leigh
Published: December 2013

A partir de microdatos de la encuesta de hogares se cuantifica el incumplimiento en Chile del salario mínimo, el número máximo de horas de trabajo, el derecho a un contrato escrito y el derecho a pensión de 1990 a 2009. Un tercio de los trabajadores sufrió algún tipo de infracción, con variaciones en el tiempo y según la norma y las características del trabajador y de la empresa. Según el análisis econométrico, la tasa de cumplimiento es menor cuando se trata de mujeres, extranjeros, indígenas y trabajadores menos instruidos, empresas más pequeñas y regiones agrícolas. Convendría investigar los efectos de la inspección del trabajo.
Trabajo por cuenta propia y monotributo en el Uruguay
Authors: AMARANTE Verónica , PERAZZO Ivone
Published: December 2013

La incorporación de los trabajadores por cuenta propia al régimen de protección social constituye un desafío importante en América Latina. En 2007 se modificó en el Uruguay un sistema específico de contribución para estos trabajadores, denominado monotributo, tras lo cual una proporción relevante de ellos puede adherirse al régimen. Este artículo presenta un análisis de las características y condiciones de trabajo de estos trabajadores en el Uruguay de 2000 a 2010 y explora la evolución del nivel de cotizaciones a la seguridad social asociada con la modificación del régimen de monotributo, así como su potencial de inclusión.
Latitudinal gradients in North American avian species richness, turnover rates and extinction probabilities
Authors: Karanth Krithi K. , Nichols James D. , Sauer John R. , Hines James E. , Yackulic Charles B.
Published: December 2013

A decline in species richness moving from equatorial regions to polar regions is a common, but not universal, macroecological pattern. Many studies have focused on this pattern, but few have focused on how the vital rates responsible for species richness patterns, local rates of species extinction and turnover, vary with latitude. We examine patterns of richness, turnover and extinction in North American avian communities inhabiting three ecoregions, using methods that account for failure to detect all species present. We use breeding bird point count data from > 1000 routes in the Breeding Bird Survey collected from 1982 to 2001 to estimate richness, extinction probability and turnover rates. Our analyses differ from others in 1) the use of annual estimates derived at specific locations rather than index data accumulated over numbers of years, 2) the use of estimators that incorporated detection probabilities and 3) a focus on dynamical processes (colonization, extinction) in addition to static patterns (species richness). We find average species richness estimates (48 to 135 species) increasing with latitude for all three regions, contradicting predictions based on the latitudinal diversity gradient. The estimated rates of extinction and turnover declined with latitude across the three ecoregions. We speculate that higher richness might be linked to periods of superabundant food supply in northern areas that support greater numbers of resident and migrant species. Our primary ecological conclusions are that the latitudinal gradient in species richness is reversed for North American birds in the studied ecoregions, and that both local extinction and turnover decrease from southern to northern latitudes. Thus, the vital rates that determine richness show evidence of greater stability and reduced dynamics in northern areas of higher richness. We recommend additional studies examining patterns of colonization, extinction and turnover in communities, that use clearly defined estimators that deal with detection probability.
Integrating phylogenetic community structure with species distribution models: an example with plants of rock barrens
Authors: Oke Oluwatobi A. , Heard Stephen B. , Lundholm Jeremy T.
Published: December 2013

Approaches using phylogenetic pattern in ecological communities to deduce processes of community assembly have been criticised as disconnected from foundations in ecological mechanism, especially with respect to lack of data about abiotic and biotic niches. These criticisms can be addressed with analyses of organismal traits that underlie environmental filtering, competitive exclusion, and other candidate processes; however, the difficulty of assembling large trait databases means that such studies remain uncommon. We suggest a synthesis of phylogenetic community structure analysis and species distribution modeling that we believe can allow inference about community processes without prohibitive data requirements. We illustrate this method for angiosperm communities of rock barrens in eastern Canada. First, we analyzed phylogenetic community structure of four rock‐barren sites at three nested spatial scales (quadrat to region). For the nine most common species in our barrens, we used regional occurrence records to build species distribution models identifying environmental drivers of the nine species’ distributions. Coefficients of these models represent implicit trait data that summarize each species’ response to the environmental drivers in the model. We then tested for phylogenetic signal in these traits, to ask whether ecological forces acting on them could be generating phylogenetic community structure. We found strong phylogenetic clustering at the quadrat level, while patterns at larger scales were complex. Our distribution model suggested drought stress as the dominant driver for distributions of all the species, consistent with local correlations with soil depth, and the species’ responses to drought showed strong phylogenetic signal. The convergence of results from phylogenetic community structure and species distribution modeling suggests that barren communities are structured at the quadrat level by environmental filtering effects of moisture stress, to which species have phylogenetically patterned responses.
Composition of Exports and Export Performance of Eurozone Countries
Authors: Wierts Peter , Van Kerkhoff Henk , De Haan Jakob
Published: December 2013

This article investigates to what extent the composition of exports is related to the export performance of eurozone countries using a data set on exports from the oldest eurozone countries to their top 20 trade partners for the period 1988–2009. The results suggest that a higher share of high technology exports in total exports is positively related to total exports. Export composition also conditions the effects of the real exchange rate and partner income growth. The effect of the real exchange rate on exports becomes smaller the higher the share of high technology exports in total exports. The effect of partner income on exports becomes larger the higher the share of high technology exports in total exports.
Guidelines on the use of extracorporeal photopheresis
Authors: Knobler R. , Berlin G. , Calzavara‐Pinton P. , Greinix H. , Jaksch P. , Laroche L. , Ludvigsson J. , Quaglino P. , Reinisch W. , Scarisbrick J. , Schwarz T. , Wolf P. , Arenberger P. , Assaf C. , Bagot M. , Barr M. , Bohbot A. , Bruckner‐Tuderman L. , Dreno B. , Enk A. , French L. , Gniadecki R. , Gollnick H. , Hertl M. , Jantschitsch C. , Jung A. , Just U. , Klemke C.‐D. , Lippert U. , Luger T. , Papadavid E. , Pehamberger H. , Ranki A. , Stadler R. , Sterry W. , Wolf I.H. , Worm M. , Zic J. , Zouboulis C.C. , Hillen U.
Published: December 2013

Background

After the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T‐cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi‐disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease.

Materials and methods

In order to provide recognized expert practical guidelines for the use of this technology for all indications the European Dermatology Forum (EDF) proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task.

Results and conclusion

These guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion.
Biological control ofRhamnus cathartica: is it feasible? A review of work done in 2002–2012
Authors: Gassmann A. , Tosevski I.
Published: December 2013

Rhamnus cathartica(common buckthorn) is a shrub (or small tree) of Eurasian origin, which has become invasive in North America. Internal feeders and sap suckers were prioritized for biological control from over 30 specialized insects identified from the target plant in its native European range. Five leaf‐feeding moths were also considered for further investigations. Field observations and preliminary host range tests with the stem‐boring beetleOberea pedemontana, the root‐boring mothSynanthedon stomoxiformis, the shoot‐tip‐boring mothSorhagenia janiszewskaeand the leaf‐feeding mothsAncylis apicella,A. unculana,Triphosa dubitata,Philereme transversataandP. vetulataconfirmed that all of these species were lacking host specificity in no‐choice conditions. Choice oviposition tests carried out with most of the prioritized species to assess their ecological host range yielded unreliable results. Three psyllids,Trichochermes walkeri,Cacopsylla rhamnicollaandTrioza rhamniare promising in terms of host specificity, but are infected with the plant disease ‘CandidatusPhytoplasma rhamni’. Fruit‐ or seed‐feeding insects may present the best potential for biological control of buckthorn in directly reducing seed set and thus seedling establishment. However, it was not possible to obtain adult fruiting trees of native North AmericanRhamnusspecies for testing. It is concluded that there are no promising arthropod agents based on what is known to date. Pathogens could offer new opportunities for biological control ofR. catharticain North America.
Comparison of sampling methods of Aphis glycines predators across the diel cycle
Authors: Woltz J. M. , Landis D. A.
Published: December 2013

Nocturnal predators are often overlooked in biological control studies, despite evidence that they can make important contributions to insect pest suppression in agroecosystems. Many sampling methods are only employed during the daytime hours due to limitations of time and labour. Additionally, different sampling methods can provide contrasting information about natural enemy community composition and relative abundance. Here, we use Aphis glycines and its arthropod predators as a model system to compare natural enemy community composition described by vacuum samples, direct observations and video observations across the diel cycle in soybean. All sampling methods identified several common taxa. Anthocorids were dominant in vacuum samples and direct observations, and both methods indicated that this taxa may be more active in the afternoon. In contrast, anthocorids were recorded infrequently on video, possibly due to their small size. On video samples, lacewing larvae were the most active taxa during the day and lacewing larvae, spiders, opiliones and carabids were the most active taxa at night. We directly observed 22 predation events on soybean aphid: 17 by anthocorids, two by chrysopid larvae, and one each by a coccinellid, spider and predatory mite. The differences between the sample methods suggest that vacuum samples may represent predator abundance more accurately, while video data may miss small predators, but can be used to better assess relative time spent foraging.
Susceptibility of small honey bee colonies to invasion by the small hive beetle, Aethina tumida (Coleoptera, Nitidulidae)
Authors: Mustafa S. G. , Spiewok S. , Duncan M. , Spooner‐Hart R. , Rosenkranz P.
Published: December 2013

Weak and small honey bee colonies are supposed to be more susceptible to infestations by the small hive beetle [Aethina tumida, small hive beetle (SHB)]. To test this, we established 24 nucleus colonies [12 with and 12 without previous SHB removal (= screening)]. Four weeks later, we compared beetle numbers and the occurrence of SHB reproduction to the corresponding full‐sized colonies. Full‐sized colonies with no screening were infested with significantly more SHBs than all other groups (mean ± standard deviation = 46.9 ± 26.7). Regardless of this, none of the full‐sized colonies showed damage or evidence of SHB reproduction. In contrast, five nucleus colonies collapsed and SHB larvae were found in an additional seven colonies. Our study demonstrates that SHB infestation levels which are harmless to full‐sized colonies may have a negative impact on small nucleus colonies.
Israeli Nurses’ Intention to Report for Work in an Emergency or Disaster
Authors: Melnikov Semyon , Itzhaki Michal , Kagan Ilya
Published: December 2013

Purpose

This study investigates the effect of personal characteristics and organizational factors on nurses’ intention to report for work in a national emergency.

Design

A convenience sample was drawn of 243 Israeli registered nurses. A structured self‐administered questionnaire collected data on (a) intention to report for work, (b) barriers preventing nurses from reporting for work, (c) perceived self‐efficacy in emergency conditions, (d) risk appraisal of health hazards, (e) knowledge of nurses’ roles in emergency work, (f) access to institutional support services, and (g) reporting to work in a past emergency.

Methods

Data were analyzed by descriptive statistics, Pearson correlation coefficients, t tests, and multiple regression analysis.

Findings

Less than half of the nurses who said they had been asked to report for work in a past emergency had actually done so. The major barrier to reporting for work was childcare demands. There was a significant correlation between perceived knowledge, risk appraisal, self‐efficacy, and intention to report. Self‐efficacy, risk appraisal, working through an earlier emergency, perceived knowledge, and full or part‐time working altogether.

Conclusions

Personal factors, such as perceived knowledge, risk appraisal, and self‐efficacy, are more important to Israeli nurses than objective barriers in preventing them from reporting for emergency work. The level of perceived knowledge as to the demands on and duties of nurses in a large‐scale emergency is low. Self‐efficacy enhancing activities need to be introduced into nurse training for emergency preparedness.

Clinical Relevance

This study makes an important contribution to research on the importance of perceived self‐efficacy in the context of disaster planning.
The Effect of Postinjury Depression on Quality of Life following Minor Injury
Authors: Richmond Therese S. , Guo Wensheng , Ackerson Theimann , Hollander Judd , Gracias Vicente , Robinson Keith , Amsterdam Jay
Published: December 2013

Purpose

To describe quality of life (QoL) in the year following minor injury and to test the hypothesis that individuals with depression in the postinjury year experience lower QoL than do individuals with no depression.

Design

Prospective, longitudinal, cohort design. A total of 275 adults were randomly selected from injured patients presenting to an urban emergency department.

Methods

All participants underwent structured psychiatric diagnostic interviews immediately after injury and at 3, 6, and 12 months. The primary outcome, QoL, was measured using the Quality of Life Index. Covariates included demographics, injury status, preinjury functional status, preinjury social support, and anticipation of problems postdischarge. The General Estimating Equation was used to compare changes in QoL between participants with and without depression over 3, 6, and 12 months, adjusting for covariates.

Results

An 18.1% proportion (95% confidence interval [CI] 13.3, 22.9%) of the sample met criteria for a mood disorder in the postinjury year. The depressed group reported a QoL that was 4.2 points (95% CI 2.8–5.6) lower in the year postinjury compared with that of the nondepressed group.

Conclusions

Depression after minor injury negatively affects QoL even a full year postinjury.

Clinical Relevance

The findings of this study show that patients who have injuries that are treated and discharged from an emergency department can have significantly lower QoL in the year after that injury that is attributed, in part, to postinjury depression. Nurses should provide anticipatory guidance to patients that they may experience feelings of sadness or being “blue,” and that if they do, they should seek care.
Issues in the timing of integrated early interventions: contributions from nutrition, neuroscience, and psychological research
Authors: Wachs Theodore D. , Georgieff Michael , Cusick Sarah , McEwen Bruce S.
Published: December 2013

A central issue when designing multidimensional biological and psychosocial interventions for children who are exposed to multiple developmental risks is identification of the age period(s) in which such interventions will have the strongest and longest lasting effects (sensitive periods). In this paper, we review nutritional, neuroscientific, and psychological evidence on this issue. Nutritional evidence is used to identify nutrient‐sensitive periods of age‐linked dimensions of brain development, with specific reference to iron deficiency. Neuroscience evidence is used to assess the importance of timing of exposures to environmental stressors for maintaining neural, neuroendocrine, and immune systems integrity. Psychological evidence illustrates the sensitivity of cognitive and social–emotional development to contextual risk and protective influences encountered at different ages. Evidence reviewed documents that the early years of life are a sensitive period when biological or psychosocial interventions or exposure to risk or protective contextual influences can produce unique long‐term influences upon human brain, neuroendocrine, and cognitive or psychosocial development. However, the evidence does not identify the early years as the sole sensitive time period within which to have a significant influence upon development. Choice of age(s) to initiate interventions should be based on what outcomes are targeted and what interventions are used.
The Effect of Cognitive Load on Decision Making with Graphically Displayed Uncertainty Information
Authors: Allen Pamela M. , Edwards John A. , Snyder Frank J. , Makinson Kevin A. , Hamby David M.
Published: December 2013

An experiment examined the ability of five graphical displays to communicate uncertainty information when end users were under cognitive load (i.e., remembering an eight‐digit number). The extent to which people could accurately derive information from the graphs and the adequacy of decisions about optimal behaviors based on the graphs were assessed across eight scenarios in which probabilistic outcomes were described. Results indicated that the load manipulation did not have an overall effect on derivation of information from the graphs (i.e., mean and probability estimation) but did suppress the ability to optimize behavioral choices based on the graph. Cognitive load affected people's use of some graphical displays (basic probability distribution function) more than others. Overall, the research suggests that interpreting basic characteristics of uncertainty data is unharmed under conditions of limited cognitive resources, whereas more deliberative processing is negatively affected.
Implementation of a multicomponent psychosocial programme for persons with dementia and their families in Norwegian municipalities: experiences from the perspective of healthcare professionals who performed the intervention
Authors: Johannessen Aud , Povlsen Lene , Bruvik Frøydis , Ulstein Ingun
Published: December 2013

Background

A randomised controlled intervention study was conducted in 17 Norwegian municipalities to provide home‐dwelling people with dementia and their families with knowledge and skills to cope with the emerging problems and stresses of everyday life. It included training health professionals to carry out the intervention. Since little is known about possible benefits for health professionals of participating in such a study in terms of knowledge and change of practice as well as their views on whether the intervention is useful, we carried out this study.

Aim

To investigate the outcome of the study from the perspective of the healthcare professionals who participated in the intervention.

Method

Interviews with 19 health professionals were performed during 2012, using three focus groups and six individual interviews. The sample was purposive and included informants aged 34–61 years from 13 municipalities.

Results

Three main categories emerged: challenges, new knowledge and service development. The category challenges details the challenges connected with professionals' participation in the intervention and how they dealt with them and is described in three subcategories. The category new knowledge demonstrates the knowledge the professionals achieved while conducting the intervention and is described through three subcategories. Service development presented how the informants' experiences could contribute to improve the provision of care and details in one subcategory.

Conclusion

The results revealed a need for more knowledge among health professionals about the situation of home‐dwelling persons with dementia and their families. The study indicated that health professionals must be more aware of these persons' abilities to find their own solutions to their problems. Structured individual interventions as well as group‐based interventions in the early stages of dementia and throughout the course of the disorder seem beneficial. There is a need for better collaboration between the specialist health services, GPs and health workers in the municipalities.
Reduced-Order Constitutive Modeling of Directionally Solidified Ni-Base Superalloys
Authors: Neal S. D. , Neu R. W.
Published: December 2013

Temperature-dependent crystal viscoplasticity models are ideal for modeling large-grained, directionally solidified Ni-base superalloys but are computationally expensive. This work explores the use of reduced-order models that are potentially more efficient with similar predictive capability of capturing temperature and orientation dependence. First, a transversely isotropic viscoplasticity model is calibrated to a directionally solidified Ni-base superalloy using the response predicted by a crystal viscoplasticity model. The unified macroscale model is capable of capturing isothermal and thermomechanical responses in addition to secondary creep behavior over the temperature range of 20–1050 °C. A second approach is an extreme reduced-order microstructure-sensitive constitutive model that uses an artificial neural network to provide a set of parameters that depend on orientation, temperature, and strain rate to give a first-order approximation of the material response using a simple constitutive model. This simple relationship is then used in a Neuber-type fatigue notch analysis to predict the local response.
Value-Based Global Optimization
Authors: Moore Roxanne A. , Romero David A. , Paredis Christiaan J. J.
Published: December 2013

In this paper, a value-based global optimization (VGO) algorithm is introduced. The algorithm uses kriging-like surrogate models and a sequential sampling strategy based on value of information (VoI) to optimize an objective characterized by multiple analysis models with different accuracies. VGO builds on two main contributions. The first contribution is a novel surrogate modeling method that accommodates data from any number of different analysis models with varying accuracy and cost. Rather than interpolating, it fits a model to the data, giving more weight to more accurate data. The second contribution is the use of VoI as a new metric for guiding the sequential sampling process for global optimization. Based on information about the cost and accuracy of each available model, predictions from the current surrogate model are used to determine where to sample next and with what level of accuracy. The cost of further analysis is explicitly taken into account during the optimization process, and no further analysis occurs if the expected value of the new information is negative. In this paper, we present the details of the VGO algorithm and, using a suite of randomly generated test cases, compare its performance with the performance of the efficient global optimization (EGO) algorithm (Jones, D. R., Matthias, S., and Welch, W. J., 1998, “Efficient Global Optimization of Expensive Black-Box Functions,” J. Global Optim., 13(4), pp. 455–492). Results indicate that the VGO algorithm performs better than EGO in terms of overall expected utility—on average, the same quality solution is achieved at a lower cost, or a better solution is achieved at the same cost.
Patient Powered Device for the Treatment of Obstructive Sleep Apnea
Authors: Christenson Katya B. , Jacquemin Joseph W. , Fannon Steve M. , Widjaja Davina A. , Sienko Kathleen H. , Chervin Ronald D.
Published: December 2013

Obstructive sleep apnea (OSA) is a common sleep disorder in which the throat repeatedly closes during sleep, interrupts breathing and then sleep, and can contribute to morbidity such as daytime sleepiness, cardiovascular consequences, and premature death. Standard treatment with a continuous positive airway pressure (CPAP) machine delivers positive pressure through a mask to splint the airway open. However, CPAP is expensive, noisy, and requires electricity, all of which can limit access and nightly adherence. A concept for a mechanical CPAP device designed to be powered by the natural work of breathing rather than an external electrical source is presented in this Design Innovation paper.
Development of the Mechanical Properties of Engineered Skin Substitutes After Grafting to Full-Thickness Wounds
Authors: Sander Edward A. , Lynch Kaari A. , Boyce Steven T.
Published: December 2013

Engineered skin substitutes (ESSs) have been reported to close full-thickness burn wounds but are subject to loss from mechanical shear due to their deficiencies in tensile strength and elasticity. Hypothetically, if the mechanical properties of ESS matched those of native skin, losses due to shear or fracture could be reduced. To consider modifications of the composition of ESS to improve homology with native skin, biomechanical analyses of the current composition of ESS were performed. ESSs consist of a degradable biopolymer scaffold of type I collagen and chondroitin-sulfate (CGS) that is populated sequentially with cultured human dermal fibroblasts (hF) and epidermal keratinocytes (hK). In the current study, the hydrated biopolymer scaffold (CGS), the scaffold populated with hF dermal skin substitute (DSS), or the complete ESS were evaluated mechanically for linear stiffness (N/mm), ultimate tensile load at failure (N), maximum extension at failure (mm), and energy absorbed up to the point of failure (N-mm). These biomechanical end points were also used to evaluate ESS at six weeks after grafting to full-thickness skin wounds in athymic mice and compared to murine autograft or excised murine skin. The data showed statistically significant differences (p <0.05) between ESS in vitro and after grafting for all four structural properties. Grafted ESS differed statistically from murine autograft with respect to maximum extension at failure, and from intact murine skin with respect to linear stiffness and maximum extension. These results demonstrate rapid changes in mechanical properties of ESS after grafting that are comparable to murine autograft. These values provide instruction for improvement of the biomechanical properties of ESS in vitro that may reduce clinical morbidity from graft loss.
Open Learning at a Distance: Lessons for Struggling MOOCs
Authors: McAndrew Patrick , Scanlon Eileen
Published: December 2013

Support for nontraditional students, team-based quality control, and assessment design are critical.
Serial Femtosecond Crystallography of G Protein–Coupled Receptors
Authors: Liu Wei , Wacker Daniel , Gati Cornelius , Han Gye Won , James Daniel , Wang Dingjie , Nelson Garrett , Weierstall Uwe , Katritch Vsevolod , Barty Anton , Zatsepin Nadia A. , Li Dianfan , Messerschmidt Marc , Boutet Sébastien , Williams Garth J. , Koglin Jason E. , Seibert M. Marvin , Wang Chong , Shah Syed T. A. , Basu Shibom , Fromme Raimund , Kupitz Christopher , Rendek Kimberley N. , Grotjohann Ingo , Fromme Petra , Kirian Richard A. , Beyerlein Kenneth R. , White Thomas A. , Chapman Henry N. , Caffrey Martin , Spence John C. H. , Stevens Raymond C. , Cherezov Vadim
Published: December 2013

G Structures

G protein–coupled receptors (GPCRs) are eukaryotic membrane proteins that have a central role in cellular communication and have become key drug targets. To overcome the difficulties of growing GPCRs crystals,

Liu
et al.

(p.
1521
) used an x-ray free-electron laser to determine a high-resolution structure of the serotonin receptor from microcrystals.
C57BL/6N Mutation in
Cytoplasmic FMRP interacting protein 2
Regulates Cocaine Response
Authors: Kumar Vivek , Kim Kyungin , Joseph Chryshanthi , Kourrich Saïd , Yoo Seung-Hee , Huang Hung Chung , Vitaterna Martha H. , Pardo-Manuel de Villena Fernando , Churchill Gary , Bonci Antonello , Takahashi Joseph S.
Published: December 2013

Not All Mice Are Equal

Different laboratories often use different strains of inbred animals, but one cannot make behavioral comparisons and assume that their reaction to interventions will necessarily be similar.

Kumar
et al.

(p.
1508
) have detected differences in cocaine response between the widely used C57BL/6N and C57BL/6J mouse strains and used quantitative trait locus analysis to identify a mutation in an inducible gene,
Cyfip
, that interacts with the Fragile X protein (FMRP) to regulate sensitivity and sensitization to cocaine through regulation of neuronal connectivity.
Arabidopsis Double-Stranded RNA Binding Protein DRB3 Participates in Methylation-Mediated Defense against Geminiviruses
Authors: Raja Priya , Jackel Jamie N. , Li Sizhun , Heard Isaac M. , Bisaro David M.
Published: December 2013

Arabidopsis
encodes five double-stranded RNA binding (DRB) proteins. DRB1 and DRB2 are involved in microRNA (miRNA) biogenesis, while DRB4 functions in cytoplasmic posttranscriptional small interfering RNA (siRNA) pathways. DRB3 and DRB5 are not involved in double-stranded RNA (dsRNA) processing but assist in silencing transcripts targeted by DRB2-associated miRNAs. The goal of this study was to determine which, if any, of the DRB proteins might also participate in a nuclear siRNA pathway that leads to geminivirus genome methylation. Here, we demonstrate that DRB3 functions with Dicer-like 3 (DCL3) and Argonaute 4 (AGO4) in methylation-mediated antiviral defense. Plants employ repressive viral genome methylation as an epigenetic defense against geminiviruses, using an RNA-directed DNA methylation (RdDM) pathway similar to that used to suppress endogenous invasive DNAs such as transposons. Chromatin methylation inhibits virus replication and transcription, and methylation-deficient host plants are hypersusceptible to geminivirus infection. Using a panel of
drb
mutants, we found that
drb3
plants uniquely exhibit a similar hypersensitivity and that viral genome methylation is substantially reduced in
drb3
compared to wild-type plants. In addition, like
dcl3
and
ago4
mutants,
drb3
plants fail to recover from infection and cannot accomplish the viral genome hypermethylation that is invariably observed in asymptomatic, recovered tissues. Small RNA analysis, bimolecular fluorescence complementation, and coimmunoprecipitation experiments show that DRB3 acts downstream of siRNA biogenesis and suggest that it associates with DCL3 and AGO4 in distinct subnuclear compartments. These studies reveal that in addition to its previously established role in the miRNA pathway, DRB3 also functions in antiviral RdDM.

IMPORTANCE
Plants use RNA-directed DNA methylation (RdDM) as an epigenetic defense against geminiviruses. RNA silencing pathways in
Arabidopsis
include five double-stranded RNA binding proteins (DRBs) related to
Drosophila
R2D2 and mammalian TRBP and PACT. While DRB proteins have defined roles in miRNA and cytoplasmic siRNA pathways, a role in nuclear RdDM was elusive. Here, we used the geminivirus system to show that DRB3 is involved in methylation-mediated antiviral defense. Beginning with a panel of
Arabidopsis drb
mutants, we demonstrated that
drb3
plants uniquely show enhanced susceptibility to geminiviruses. Further, like
dcl3
and
ago4
mutants,
drb3
plants fail to hypermethylate the viral genome, a requirement for host recovery. We also show that DRB3 physically interacts with the RdDM pathway components DCL3 and AGO4 in the nucleus. This work highlights the utility of geminiviruses as models for
de novo
RdDM and places DRB3 protein in this fundamental epigenetic pathway.
Quantitative Characterization of Defective Virus Emergence by Deep Sequencing
Authors: Timm Collin , Akpinar Fulya , Yin John
Published: December 2013

Populations of RNA viruses can spontaneously produce variants that differ in genome size, sequence, and biological activity. Defective variants that lack essential genes can nevertheless reproduce by coinfecting cells with viable virus, a process that interferes with virus growth. How such defective interfering particles (DIPs) change in abundance and biological activity within a virus population is not known. Here, a prototype RNA virus, vesicular stomatitis virus (VSV), was cultured for three passages on BHK host cells, and passages were subjected to Illumina sequencing. Reads from the initial population, when aligned to the full-length viral sequence (11,161 nucleotides [nt]), distributed uniformly across the genome. However, during passages two plateaus in read counts appeared toward the 5′ end of the negative-sense viral genome. Analysis by normalization and a simple sliding-window approach revealed plateau boundaries that suggested the emergence and enrichment of at least two truncated species having medium (∼5,900 nt) and short (∼4,000 nt) genomes. Relative measures of full-length and truncated species based on read counts were validated by quantitative reverse transcription-PCR (qRT-PCR). Limit-of-detection analysis suggests that deep sequencing can be more sensitive than complementary measures for detecting and quantifying defective particles in a population. Further, particle counts from transmission electron microscopy, coupled with infectivity assays, linked the rise in smaller genomes with an increase in truncated particles and interference activity. In summary, variation in deep sequencing coverage simultaneously shows the size, location, and relative level of truncated-genome variants, revealing a level of population heterogeneity that is masked by other measures of viral genomes and particles.

IMPORTANCE
We show how deep sequencing can be used to characterize the emergence, diversity, and relative abundance of truncated virus variants in virus populations. Adaptation of this approach to natural isolates may elucidate factors that influence the stability and persistence of virus populations in nature.
Pathogenic Mutations within the Hydrophobic Domain of the Prion Protein Lead to the Formation of Protease-Sensitive Prion Species with Increased Lethality
Authors: Coleman Bradley M. , Harrison Christopher F. , Guo Belinda , Masters Colin L. , Barnham Kevin J. , Lawson Victoria A. , Hill Andrew F.
Published: December 2013

Prion diseases are a group of fatal and incurable neurodegenerative diseases affecting both humans and animals. The principal mechanism of these diseases involves the misfolding the host-encoded cellular prion protein, PrP
C
, into the disease-associated isoform, PrP
Sc
. Familial forms of human prion disease include those associated with the mutations G114V and A117V, which lie in the hydrophobic domain of PrP. Here we have studied the murine homologues (G113V and A116V) of these mutations using cell-based and animal models of prion infection. Under normal circumstances, the mutant forms of PrP
C
share similar processing, cellular localization, and physicochemical properties with wild-type mouse PrP (MoPrP). However, upon exposure of susceptible cell lines expressing these mutants to infectious prions, very low levels of protease-resistant aggregated PrP
Sc
are formed. Subsequent mouse bioassay revealed high levels of infectivity present in these cells. Thus, these mutations appear to limit the formation of aggregated PrP
Sc
, giving rise to the accumulation of a relatively soluble, protease sensitive, prion species that is highly neurotoxic. Given that these mutations lie next to the glycine-rich region of PrP that can abrogate prion infection, these findings provide further support for small, protease-sensitive prion species having a significant role in the progression of prion disease and that the hydrophobic domain is an important determinant of PrP conversion.

IMPORTANCE
Prion diseases are transmissible neurodegenerative diseases associated with an infectious agent called a prion. Prions are comprised of an abnormally folded form of the prion protein (PrP) that is normally resistant to enzymes called proteases. In humans, prion disease can occur in individuals who inherited mutations in the prion protein gene. Here we have studied the effects of two of these mutations and show that they influence the properties of the prions that can be formed. We show that the mutants make highly infectious prions that are more sensitive to protease treatment. This study highlights a certain region of the prion protein as being involved in this effect and demonstrates that prions are not always resistant to protease treatment.
Respiratory Syncytial Virus Infection, TLR3 Ligands, and Proinflammatory Cytokines Induce CD161 Ligand LLT1 Expression on the Respiratory Epithelium
Authors: Satkunanathan Stifani , Kumar Naveenta , Bajorek Monika , Purbhoo Marco A. , Culley Fiona J.
Published: December 2013

During respiratory-virus infection, excessive lymphocyte activation can cause pathology both in acute infection and in exacerbations of chronic respiratory diseases. The costimulatory molecule CD161 is expressed on lymphocyte subsets implicated in promoting respiratory inflammation, including Th2, Th17, mucosally associated invariant T (MAIT) cells, and type 2 innate lymphoid cells. We asked whether the CD161 ligand LLT1 could be expressed on respiratory epithelial cells following respiratory-virus infection as a mechanism by which respiratory-virus infection could promote activation of proinflammatory lymphocytes. In response to respiratory syncytial virus (RSV) infection, expression of LLT1 was upregulated in the BEAS-2B respiratory epithelial cell line and primary human bronchial epithelial cells. Imaging studies revealed that LLT1 expression increased in both RSV-infected and cocultured uninfected cells, suggesting that soluble factors produced during infection stimulate LLT1 expression. TLR3 and TLR2/6 ligands led to a rapid increase in LLT1 mRNA in respiratory epithelial cells, as did the proinflammatory cytokines type I interferons, interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNF-α), which are produced early in respiratory-virus infection. Immunohistochemistry confirmed the increase in LLT1 protein on the epithelial cell surface, and live-cell confocal microscopy demonstrated accumulation of epithelial LLT1 at synapses formed with CD161+T lymphocytes. LLT1 expression by the respiratory epithelium in response to respiratory-virus infection and inflammatory cytokines represents a novel link between innate immunity and lymphocyte activation. As a regulator of CD161+proinflammatory lymphocytes, LLT1 could be a novel therapeutic target in inflammation caused by respiratory-virus infection.

IMPORTANCEThe immune response to respiratory-virus infection is essential for clearing the pathogen but, if excessive, can lead to tissue damage and obstruction of the airways. How viral infection activates immune cells in the lungs is not fully understood. Here, we show that LLT1 can be expressed in lung cells in response to infection. LLT1 triggers CD161, a receptor on inflammatory immune cells. This mechanism may promote activation of immune cells in the lungs in viral infection and could be a novel target for therapies aimed at reducing lung inflammation.