bluuebunny/crossref_metadata_2025 huggingface dataset:
Leishmaniasis
Authors: Von Stebut Esther
Published: February 2015

Infections with Leishmania spp. rank among the top three most common travel‐associated dermatoses. Depending on the country where the infection was acquired and the patient's immune status, different disease manifestations may be observed. Ninety percent of cases present as cutaneous leishmaniasis, but the infection may also affect internal organs (visceral leishmaniasis). Without treatment, the latter is often fatal. Intermediate types include recurrent, diffuse, or mucocutaneous forms. Nodular lesions on exposed skin with a tendency to ulcerate over time in combination with a travel history should therefore prompt workup for leishmaniasis. The diagnosis is made through histology, parasite culture, and PCR using biopsy material. Therapeutic options range from local therapies in cases with singular lesions to systemic therapy in patients with more severe forms. The present review discusses the most important clinical features, details about diagnostic measures, and current therapeutic approaches.
Roles of p38α mitogen‐activated protein kinase in mouse models of inflammatory diseases and cancer
Authors: Gupta Jalaj , Nebreda Angel R.
Published: February 2015

The p38α mitogen‐activated protein kinase pathway not only regulates the production of inflammatory mediators, but also controls processes related to tissue homeostasis, such as cell proliferation, differentiation and survival, which are often disrupted during malignant transformation. The versatility of this signaling pathway allows for the regulation of many specific functions depending on the cell type and context. Here, we discuss mouse models that have been used to identify in vivo functions of p38α signaling in the pathogenesis of inflammatory diseases and cancer. Experiments using genetically modified mice and pharmacological inhibitors support that targeting the p38α pathway could be therapeutically useful for some inflammatory diseases and tumor types.
Occurrence of demersal fishes in relation to near‐bottom oxygen levels within the California Current large marine ecosystem
Authors: Keller Aimee A. , Ciannelli Lorenzo , Wakefield W. Waldo , Simon Victor , Barth John A. , Pierce Stephen D.
Published: February 2015

Various ocean‐climate models driven by increased greenhouse gases and higher temperatures predict a decline in oceanic dissolved oxygen (DO) as a result of greater stratification, reduced ventilation below the thermocline, and decreased solubility at higher temperatures. Since spreading of low oxygen waters is underway and predicted to increase, understanding impacts on higher trophic levels is essential. Within the California Current System, shoaling of the oxygen minimum zone (OMZ) is expected to produce complex changes. Onshore movement of the OMZ could lead to habitat compression for species with higher oxygen requirements while allowing expansion of species tolerant of low bottom DO. As part of annual groundfish surveys, we sampled catch across a range of conditions from the upper to the lower limit of the OMZ and shoreward across the continental shelf of the US west coast. DO ranged from 0.02 to 4.25 mL L−1 with 642 stations (of 1020 sampled) experiencing hypoxic conditions in 2008–2010. Catch and species richness exhibited significant and positive relationships with near‐bottom oxygen concentration. The probability of occurrence was estimated for four species (spotted ratfish, petrale sole, greenstriped rockfish and Dover sole) using a binomial Generalized Additive Model. The models for each species included terms for position, day of the year, salinity, near‐bottom temperature and the interaction term between depth and near‐bottom DO. Spotted ratfish and petrale sole were sensitive to changes in near‐bottom oxygen, while greenstriped rockfish and Dover sole show no changes in probability of occurrence in relation to changes in oxygen concentration.
Effects of climate on temporal variation in the abundance and distribution of the demersal fish assemblage in the Tsushima Warm Current region of the Japan Sea
Authors: Tu Chen‐Yi , Tian Yongjun , Hsieh Chih‐Hao
Published: February 2015

In the present study, we examined the effects of climate on temporal variation in the abundance and geographical distribution of demersal fishes at both interannual and decadal scales in the Tsushima Warm Current region of the Japan Sea using single‐trawler fishery data (1972–2002). This single‐trawler fishery targeted multiple species with different geographical affinities and life history traits. Thus, these data were suitable for examining the biological mechanisms that underlie how species respond to climate variability. Our results indicate that the distributional changes of species in response to decadal climate variability are best explained by asymptotic length, which indicates that warming has greater negative effects on larger fishes in the Japan Sea. However, none of the variables examined (including geographical affinity, asymptotic length and age at maturation) could explain the shift in abundance at interannual or decadal scales. It should be noted that life history traits and geographical affinities only provide partial explanations of the responses of species to environmental variability, thereby suggesting that other factors, such as interactions among species, may be involved in mediating species responses.
The cold‐water climate shield: delineating refugia for preserving salmonid fishes through the 21st century
Authors: Isaak Daniel J. , Young Michael K. , Nagel David E. , Horan Dona L. , Groce Matthew C.
Published: February 2015

The distribution and future fate of ectothermic organisms in a warming world will be dictated by thermalscapes across landscapes. That is particularly true for stream fishes and cold‐water species like trout, salmon, and char that are already constrained to high elevations and latitudes. The extreme climates in those environments also preclude invasions by most non‐native species, so identifying especially cold habitats capable of absorbing future climate change while still supporting native populations would highlight important refugia. By coupling crowd‐sourced biological datasets with high‐resolution stream temperature scenarios, we delineate network refugia across >250 000 stream km in the Northern Rocky Mountains for two native salmonids—bull trout (BT) and cutthroat trout (CT). Under both moderate and extreme climate change scenarios, refugia with high probabilities of trout population occupancy (>0.9) were predicted to exist (33–68 BT refugia; 917–1425 CT refugia). Most refugia are on public lands (>90%) where few currently have protected status in National Parks or Wilderness Areas (<15%). Forecasts of refuge locations could enable protection of key watersheds and provide a foundation for climate smart planning of conservation networks. Using cold water as a ‘climate shield’ is generalizable to other species and geographic areas because it has a strong physiological basis, relies on nationally available geospatial data, and mines existing biological datasets. Importantly, the approach creates a framework to integrate data contributed by many individuals and resource agencies, and a process that strengthens the collaborative and social networks needed to preserve many cold‐water fish populations through the 21st century.
Neutrophil CD64 level as a rapid and promising diagnostic tool for infectious diseases in elderly patients
Authors: Otsuki Nozomi , Tsutani Hiroshi , Matsui Toshihiro , Iwasaki Hiromichi , Ueda Takanori
Published: February 2015

Aim

We examined the utility of the neutrophil CD64 level as a rapid and sensitive diagnostic marker for infections in febrile aged patients.

Methods

The expression level of CD64 per neutrophil was quantitatively measured with flow cytometry using a QuantiBrite kit in samples from febrile (aged >65 years) patients. Information about the presence or absence of infectious disease was retrospectively obtained from each patient's medical record in which attending physicians were obliged to write down a tentative diagnosis after resolution of manifestations.

Results

With receiver operating characteristic curve evaluation using the results, a CD64 level >2000 molecules per neutrophil was sensitive and specific for detecting infection. Among 102 patients suspected of having infection, 72 patients were diagnosed with infectious diseases, and 30 patients had non‐infectious diseases. The sensitivity and specificity of determination of the neutrophil CD64 level were 88% and 63%, respectively. However, considering the high frequency of infections in elderly patients (71% in the present study), the post‐test probability reached as high as 93%. The positive likelihood ratio was 2.4, and the negative likelihood ratio was 0.2.

Conclusions

Considering the frequency of infectious diseases in elderly patients, determination of the neutrophil CD64 level helps detect infectious diseases. Geriatr Gerontol Int 2015; 16: 307–313.
God in the World: Lenin, Hegel, and the God‐Builders
Authors: Boer Roland
Published: February 2015

This article reassesses a rarely noted aspect of the Russian Revolution: the long interaction between Lenin and Anatoly Lunacharsky, the ‘God‐builder’. It traces the way Lunacharsky first outlined the God‐building position in his Religion and Socialism (1908, 1911), a text virtually lost to scholarship and interpretations of the Russian revolution. It explores Lenin's initial condemnation, for political but above all theoretical reasons, only to find him reassessing his whole argument six years later in light of his re‐engagement with Hegel in 1914. Seeing that his earlier condemnation no longer held, Lenin's response to Lunacharsky's God‐building undergoes a noticeable shift. He now realizes that marginal forms of interaction with religion may sit well with, if not lead to, communism. An examination of Lunacharsky's own perseverance with God‐building after he was appointed Commissar for Enlightenment in the new Soviet state, and of Lenin's awareness and tacit allowance for such expressions, indicate a more complex and ambivalent approach to religion on Lenin's part.
A parent‐based intervention to promote healthy eating and active behaviours in pre‐school children: evaluation of theMEND2–4 randomized controlled trial
Authors: Skouteris H. , Hill B. , McCabe M. , Swinburn B. , Busija L.
Published: February 2015

Background

There is a paucity of studies evaluating targeted obesity prevention interventions in pre‐school children.

Objectives

We conducted a randomized controlled trial to evaluate the efficacy of a parent‐based obesity prevention intervention for pre‐schoolers –MEND(Mind,Exercise,Nutrition … DoIt!) 2–4 on child diet, eating habits, physical activity/sedentary behaviours, and body mass index (BMI).

Methods

Parent–child dyads attended 10 weekly 90‐min workshops relating to nutrition, physical activity and behaviours, including guided active play and healthy snack time. Assessments were conducted at baseline, immediately post‐intervention, and 6 and 12 months post‐intervention; child intake of vegetables, fruit, beverages, processed snack foods, fussiness, satiety responsiveness, physical activity, sedentary behaviour and neophobia were assessed via parent proxy report. Parent and child height and weight were measured.

Results

Two hundred one parent–child dyads were randomized to intervention (n = 104) and control (n = 97). Baseline mean child age was 2.7 (standard deviation [SD] 0.6) years, and childBMI‐for‐agez‐score (World Health Organization) was 0.66 (SD0.88). We found significant positive group effects for vegetable (P = 0.01) and snack food (P = 0.03) intake, and satiety responsiveness (P = 0.047) immediately post‐intervention. At 12 months follow‐up, intervention children exhibited less neophobia (P = 0.03) than controls.

Conclusion

Future research should focus on additional strategies to support parents to continue positive behaviour change. ACTRN12610000200088.
MRI Assessment of Ablation‐Induced Scarring in Atrial Fibrillation: Analysis from the DECAAF Study
Authors: AKOUM NAZEM , WILBER DAVID , HINDRICKS GERHARD , JAIS PIERRE , CATES JOSH , MARCHLINSKI FRANCIS , KHOLMOVSKI EUGENE , BURGON NATHAN , HU NAN , MONT LLUIS , DENEKE THOMAS , DUYTSCHAEVER MATTIAS , NEUMANN THOMAS , MANSOUR MOUSSA , MAHNKOPF CHRISTIAN , HUTCHINSON MATHEW , HERWEG BENGT , DAOUD EMILE , WISSNER ERIK , BRACHMANN JOHANNES , MARROUCHE NASSIR F.
Published: February 2015

MRI Assessment of Ablation‐Induced Scarring in Atrial Fibrillation

Background

There is limited knowledge on the extent and location of scarring that results from catheter ablation and its role in suppressing atrial fibrillation (AF). We examined the effect of atrial fibrosis and ablation‐induced scarring on catheter ablation outcomes in AF.

Methods

We conducted a prospective multicenter study that enrolled 329 AF patients presenting for catheter ablation. Delayed enhancement magnetic resonance imaging (DE‐MRI) of the left atrium was obtained preablation. Scarring was evaluated in 177 patients with a DE‐MRI scan obtained 90 days postablation. We evaluated residual fibrosis, defined as preablation atrial fibrosis not covered by ablation scar. The primary outcome was freedom from recurrent atrial arrhythmia.

Results

In the analysis cohort of 177 patients, preablation fibrosis was 18.7 ± 8.7% of the atrial wall. Ablation aimed at pulmonary vein (PV) isolation was performed in 163 patients (92.1%). Ablation‐induced scar averaged 10.6 ± 4.4% of the atrial wall. Scarring completely encircled all 4 PVs only in 12 patients (7.3%). Residual fibrosis was calculated at 15.8 ± 8.0%. At 325 days follow‐up, 35% of patients experienced recurrent arrhythmia. Multivariable Cox proportional hazards models demonstrated that baseline atrial fibrosis (HR and 95% CIs) (1.09 [1.06–1.12], P < 0.001) and residual fibrosis (1.09 [1.05–1.13], P < 0.001) were associated with atrial arrhythmia recurrence, while PV encirclement and overall scar were not.

Conclusions

Catheter ablation of AF targeting PVs rarely achieves permanent encircling scar in the intended areas. Overall atrial fibrosis present at baseline and residual fibrosis uncovered by ablation scar are associated with recurrent arrhythmia.
MiR‐320a contributes to atherogenesis by augmenting multiple risk factors and down‐regulating SRF
Authors: Chen Chen , Wang Yan , Yang Shenglan , Li Huaping , Zhao Gang , Wang Feng , Yang Lei , Wang Dao Wen
Published: February 2015

Atherosclerosis progress is regulated by a variety of factors. Here, we show that miR‐320a, an intergenic miRNA, is markedly elevated in the peripheral blood of coronary heart disease patients and high‐risk patients. Microarray analysis and qRT‐PCR assays showed that circulating miRNA‐320a was highly expressed in coronary artery disease patients. In vivo study showed that overexpression of miR‐320a resulted in significant increase in levels of plasma lipid (total cholesterol, Triglyceride and low‐density lipoprotein) and serum inflammatory cytokines (IL‐6, MCP‐1, sICAM, pSelectin, TNF‐α and fibrinogen). In ApoE−/− mice, miR‐320a expression attenuates endothelium cell function and promotes atherogenesis. Bioinformatics analysis identified serum response factor as a potential target for miR‐320a, which was validated by luciferase reporter activity assay and western‐blot in vitro and in vivo. Moreover, miR‐320a expression inhibits human‐derived endothelium cell proliferation and induces apoptosis. We also found that SP1 transcriptionally up‐regulates hsa‐miR‐320a expression. Our observations indicate that miR‐320a is a key regulator contributing to multiple aspects of atherogenesis.
Autophagy and mitochondrial remodelling in mouse mesenchymal stromal cells challenged with Staphylococcus epidermidis
Authors: Gorbunov Nikolai V. , McDaniel Dennis P. , Zhai Min , Liao Pei‐Jyun , Garrison Bradley R. , Kiang Juliann G.
Published: February 2015

The bone marrow stroma constitutes the marrow‐blood barrier, which sustains immunochemical homoeostasis and protection of the haematopoietic tissue in sequelae of systemic bacterial infections. Under these conditions, the bone marrow stromal cells affected by circulating bacterial pathogens shall elicit the adaptive stress‐response mechanisms to maintain integrity of the barrier. The objective of this communication was to demonstrate (i) that in vitro challenge of mesenchymal stromal cells, i.e. colony‐forming unit fibroblasts (CFU‐F), with Staphylococcus epidermidis can activate the autophagy pathway to execute antibacterial defence response, and (ii) that homoeostatic shift because of the bacteria‐induced stress includes the mitochondrial remodelling and sequestration of compromised organelles via mitophagy. Implication of Drp1 and PINK1–PARK2‐dependent mechanisms in the mitophagy turnover of the aberrant mitochondria in mesenchymal stromal cells is investigated and discussed.
HIV and STI testing in older adults: an integrative review
Authors: Tillman Jessica L. , Mark Hayley D.
Published: February 2015

Aims and objectives

To examine the frequency of human immunodeficiency virus testing and sexually transmitted infection testing among older adults (50 years and older), present factors related to human immunodeficiency virus and sexually transmitted infection testing among older adults, and summarise the perspectives and practices of older adults and health care providers related to sexual health communication.

Background

Reported cases of sexually transmitted infections and human immunodeficiency virus among older adults have increased, therefore refuting the stereotype of the sexually inactive older adult.

Design

Integrative review.

Methods

Database searches in PubMed, EMBASE, CINAHL, and Web of Science; manual reference list searches; and database searches for articles that cited previously identified articles.

Results

There is limited research on this topic and considerable diversity in the populations studied and outcomes measured. The search process yielded 20 articles meeting the eligibility criteria. Human immunodeficiency virus and sexually transmitted infection testing of older adults are infrequent. Human immunodeficiency virus testing among older adults is associated with perceived risk of contracting human immunodeficiency virus and influenced by encouragement from health care providers. Sexually transmitted infection testing due to genital symptoms is more likely than asymptomatic screening. Few providers collect routine sexual histories from older adult patients, although older adults are receptive to sexual history taking.

Conclusions

There are missed opportunities to identify sexually transmitted infections and human immunodeficiency virus in older adults. Stereotypes and assumptions have hindered providers from identifying and testing older adults at risk for human immunodeficiency virus and sexually transmitted infections.

Relevance to clinical practice

Sexual health assessment is essential to comprehensive health care. A sexual history provides information that may indicate human immunodeficiency virus and sexually transmitted infection testing. Detection and treatment of human immunodeficiency virus and sexually transmitted infections will break the chain of infection and improve quality of life.
PATIENTS’ AND RELATIVES’ EXPERIENCES OF PERITONITIS WHEN USING PERITONEAL DIALYSIS
Authors: Baillie Jessica , Lankshear Annette
Published: February 2015

Background

Internationally, increasing numbers of patients are requiring treatment for end‐stage kidney disease and greater use of peritoneal dialysis is thus being promoted. However, peritonitis can be a significant problem in this population. It is the leading cause of technique failure in patients using peritoneal dialysis and results in considerable morbidity and mortality. There is a dearth of research exploring patients’ and their families’ experiences of peritonitis.

Objectives

The aim of this paper is to explore patients’ and their families’ perspectives and experiences of peritonitis.

Design

An ethnographic study was conducted in 2011 in the United Kingdom.

Participants

Sixteen patients and nine of their relatives were recruited through purposive and convenience sampling.

Approach

In‐depth interviews were undertaken with patients and their families, who were also observed using peritoneal dialysis in their homes. The data were analysed thematically using Wolcott's (1994) three‐stage approach.

Results

This article describes four themes: learning about the risk of peritonitis; measures taken to prevent the infection; how participants monitored continuously for signs and symptoms of the infection; how they then identified and intervened once peritonitis was suspected. Overall, peritonitis was associated with fear and uncertainty, pain and learning from episodes of the infection.

Conclusions

Overall, peritonitis was a distressing experience that participants sought to prevent. However, there was some confusion amongst participants about the signs and symptoms of the infection and further education for patients and their families is thus crucial.
Diversity of nitrogen assimilation pathways among microbial photosynthetic eukaryotes
Authors: Terrado Ramon , Monier Adam , Edgar Robyn , Lovejoy Connie
Published: February 2015

In an effort to better understand the diversity of genes coding for nitrogen (N) uptake and assimilation pathways among microalgae, we analyzed the transcriptomes of five phylogenetically diverse single celled algae originally isolated from the same high arctic marine region. The five photosynthetic flagellates (a pelagophyte, dictyochophyte, chrysoph‐yte, cryptophyte and haptophyte) were grown on standard media and media with only urea or nitrate as a nitrogen source; cells were harvested during late exponential growth. Based on homolog protein sequences, transcriptomes of each alga were interrogated to retrieve genes potentially associated with nitrogen uptake and utilization pathways. We further investigated the phylogeny of poorly characterized genes and gene families that were identified. While the phylogeny of the active urea transporter (DUR3) was taxonomically coherent, those for the urea transporter superfamily, putative nitrilases and amidases indicated complex evolutionary histories, and preliminary evidence for horizontal gene transfers. All five algae expressed genes for ammonium assimilation and all but the chrysophyte expressed genes involved in nitrate utilization and the urea cycle. Among the four algae with nitrate transporter transcripts, we detected lower expression levels in three of these (the dictyochophyte, pelagophyte, and cryptophyte) grown in the urea only medium compared with cultures from the nitrate only media. The diversity of N pathway genes in the five algae, and their ability to grow using urea as a nitrogen source, suggest that these flagellates are able to use a variety of organic nitrogen sources, which would be an advantage in an inorganic nitrogen ‐ limited environment, such as the Arctic Ocean.
Meiotic genes and sexual reproduction in the green algal class Trebouxiophyceae (Chlorophyta)
Authors: Fučíková Karolina , Pažoutová Marie , Rindi Fabio
Published: February 2015

Sexual reproduction is widespread in eukaryotes and is well documented in chlorophytan green algae. In this lineage, however, the Trebouxiophyceae represent a striking exception: in contrast to its relatives Chlorophyceae and Ulvophyceae this group appears to be mostly asexual, as fertilization has been rarely observed. Assessments of sexual reproduction in the Trebouxiophyceae have been based on microscopic observation of gametes fusing. New genomic data offer now the opportunity to check for the presence of meiotic genes, which represent an indirect evidence of a sexual life cycle. Using genomic and transcriptomic data for 12 taxa spanning the phylogenetic breadth of the class, we tried to clarify whether genuine asexuality or cryptic sexuality is the most likely case for the numerous putatively asexual trebouxiophytes. On the basis of these data and a bibliographic review, we conclude that the view of trebouxiophytes as primarily asexual is incorrect. In contrast to the limited number of reports of fertilization, meiotic genes were found in all genomes and transcriptomes examined, even in species presumed asexual. In the taxa examined the totality or majority of the genes were present, Helicosporidium and Auxenochlorella being the only partial exceptions (only four genes present). The evidence of sex provided by the meiotic genes is phylogenetically widespread in the class and indicates that sexual reproduction is not associated with any particular morphological or ecological trait. On the basis of the results, we expect that the existence of the meiotic genes will be documented in all trebouxiophycean genomes that will become available in the future.
Stochastic modelling of shifts in allele frequencies reveals a strongly polygynous mating system in the re‐introduced Asiatic wild ass
Authors: Renan Sharon , Greenbaum Gili , Shahar Naama , Templeton Alan R. , Bouskila Amos , Bar‐David Shirli
Published: February 2015

Small populations are prone to loss of genetic variation and hence to a reduction in their evolutionary potential. Therefore, studying the mating system of small populations and its potential effects on genetic drift and genetic diversity is of high importance for their viability assessments. The traditional method for studying genetic mating systems is paternity analysis. Yet, as small populations are often rare and elusive, the genetic data required for paternity analysis are frequently unavailable. The endangered Asiatic wild ass (Equus hemionus), like all equids, displays a behaviourally polygynous mating system; however, the level of polygyny has never been measured genetically in wild equids. Combining noninvasive genetic data with stochastic modelling of shifts in allele frequencies, we developed an alternative approach to paternity analysis for studying the genetic mating system of the re‐introduced Asiatic wild ass in the Negev Desert, Israel. We compared the shifts in allele frequencies (as a measure of genetic drift) that have occurred in the wild ass population since re‐introduction onset to simulated scenarios under different proportions of mating males. We revealed a strongly polygynous mating system in which less than 25% of all males participate in the mating process each generation. This strongly polygynous mating system and its potential effect on the re‐introduced population's genetic diversity could have significant consequences for the long‐term persistence of the population in the Negev. The stochastic modelling approach and the use of allele‐frequency shifts can be further applied to systems that are affected by genetic drift and for which genetic data are limited.
Proven and probable invasive fungal infections in children with acute lymphoblastic leukaemia: results from an university hospital, 2005–2013
Authors: Sahbudak Bal Zumrut , Yilmaz Karapinar Deniz , Karadas Nihal , Sen Semra , Onder Sivis Zuhal , Akinci Ayse B. , Balkan Can , Kavakli Kaan , Vardar Fadil , Aydinok Yesim
Published: February 2015

Despite improvements in diagnosis and treatment, invasive fungal infections (IFIs) are still a major cause of morbidity and mortality in immunocompromised patients. The data on IFI among children with acute lymphoblastic leukaemia (ALL) are still scarce, and our aim was to estimate the risk, aetiology and outcome of proven and probable IFIs in children with ALL who did not receive primary prophylaxis over an 8‐year period. Between January 2005 and February 2013, 125 children who were treated for ALL at the Pediatric Hematology Department of the Medical School of Ege University were retrospectively reviewed. Proven and probable IFIs were defined according to revised definitions of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. The proven and probable IFI incidence was 30/125 (24%). Profound neutropenia was detected in 18 (60%) patients, and prolonged neutropenia was detected in 16 (53.3%) of the patients. The most isolated agents were non‐albicans Candida spp. The crude and attributable mortality was 20% and 13.3% respectively. Profound neutropenia was associated with mortality (P < 0.05). The younger patients were especially at risk for proven IFI. Prolonged neutropenia, to be in the induction phase of chemotherapy, and profound neutropenia were found to be the most common predisposing factors for IFI episodes.
Changes in southern Piedmont grassland community structure and nutritive quality with future climate scenarios of elevated tropospheric ozone and altered rainfall patterns
Authors: Gilliland N. J. , Chappelka A. H. , Muntifering R. B. , Ditchkoff S. S.
Published: February 2015

Forage species common to the southern USA Piedmont region, Lolium arundinacea, Paspalum dilatatum, Cynodon dactylon and Trifolium repens, were established in a model pasture system to test the future climate change scenario of increasing ozone exposure in combination with varying rainfall amounts on community structure and nutritive quality. Forages were exposed to two levels of ozone [ambient (non‐filtered; NF) and twice ambient (2×) concentrations] with three levels of precipitation (average or ±20% of average) in modified open‐top chambers (OTCs) from June to September 2009. Dry matter (DM) yield did not differ over the growing season between forage types, except in primary growth grasses where DM yield was higher in 2× than NF treatment. Primary growth clover decreased in nutritive quality in 2× ozone because of increased concentrations of neutral detergent fibre (NDF), acid detergent fibre (ADF) and acid detergent lignin (ADL). Re‐growth clover exhibited the largest decrease in nutritive quality, whereas grasses were not adversely affected in 2× ozone. Re‐growth grasses responded positively to 2× ozone exposure, as indicated in increased relative food value (RFV) and percentage crude protein (CP) than NF‐exposed re‐growth grasses. Effects of precipitation were not significant over the growing season for primary or re‐growth forage, except in primary growth grasses where DM yield was higher in chambers with above average (+20%) precipitation. Total canopy cover was significantly higher over the growing season in chambers receiving above average precipitation, but no significant effects were observed with ozone. Results indicate shifts in plant community structure and functioning related to mammalian herbivore herbivory in future climate change scenarios.
Do all patients with idiopathic pulmonary fibrosis warrant a trial of therapeutic intervention? A pro‐con perspective
Authors: Moodley Yuben , Corte Tamera , Richeldi Luca , King Talmadge E.
Published: February 2015

Idiopathic pulmonary fibrosis (IPF) is an incurable condition that is characterized by progressive pulmonary fibrosis, architectural distortion of the lung and loss of gas exchange units. Until recently, there was no effective treatment for this condition. However, there were two landmark trials published earlier this year, which have changed the management of this condition. Pirfenidone (Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis trial) and nintedanib (Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis‐1 and ‐2 trials) have both demonstrated positive outcomes in patients with IPF. In this perspective, we critically discuss the role of these agents in IPF and in the broader pulmonary fibrosis population.
Delayed access to treatments for rare diseases: Who's to blame?
Authors: Feltmate Karen , Janiszewski Peter M. , Gingerich Sheena , Cloutier Michael
Published: February 2015

The development and commercialization of drugs for rare diseases, termed ‘orphan drugs’, has historically been economically unattractive. However, because of the introduction of legislation that provides financial and regulatory incentives for the development of orphan drugs, new developments are making their way through the regulatory approval processes. Unfortunately, delays in availability of new drugs for treating rare disease continue to persist. This paper reviews the approach of several regulatory jurisdictions to orphan drugs in an effort to determine their relative effectiveness in providing patient access. Generally speaking, regulatory authorities across jurisdictions have recognized the need to enhance timely access to safe, effective treatment for patients with rare diseases and have been able to shift the approval timelines for access to new care. The greater impediment to orphan drug access appears to be funding, particularly in publicly sponsored health‐care systems. Redundancies in federal and provincial reviews of orphan drugs can result in significant delays in access to new drugs. Clearly, more must be done to accelerate access to the treatments so desperately needed by patients. Public payers must be held accountable for their process and decisions—especially for rare disease therapies.
A Hybrid Link‐Node Approach for Finding Shortest Paths in Road Networks with Turn Restrictions
Authors: Li Qingquan , Chen Bi Yu , Wang Yafei , Lam William H. K.
Published: February 2015

Turn restrictions, such as ‘no left turn’ or ‘no U‐turn’, are commonly encountered in real road networks. These turn restrictions must be explicitly considered in the shortest path problem and ignoring them may lead to infeasible paths. In the present study, a hybrid link‐node Dijkstra's (HLND) algorithm is proposed to exactly solve the shortest path problem in road networks with turn restrictions. A new hybrid link–node labelling approach is devised by using a link–based labelling strategy at restricted nodes with turn restrictions, and a node‐based labelling strategy at unrestricted nodes without turn restrictions. Computational results for several real road networks show that the proposed HLND algorithm obtains the same optimal results as the link‐based Dijkstra's algorithm, while having a similar computational performance to the classical node‐based Dijkstra's algorithm.
Frege on Existence and Non‐existence
Authors: Green Karen
Published: February 2015

Despite its importance for early analytic philosophy, Gottlob Frege's account of existence statements, according to which they classify concepts, has been thought to succumb to a number of well‐worn criticisms. This article does two things. First, it argues that, by remaining faithful to the letter of Frege's claim that concepts are functions, the Fregean account can be saved from many of the standard criticisms. Second, it examines the problem that Frege's account fails to generalize to cases which involve definite descriptions and proper names. To deal with this the proffered analysis deviates from the letter of Frege's views, while remaining within its spirit. It proposes, in opposition to Frege, that expressions which grammatically look like singular terms should not always be read as referring to objects, but are sometimes best analysed as indicating functions.
Spatial analysis of under‐5 mortality and potential risk factors in the Basse Health and Demographic Surveillance System, the Gambia
Authors: Quattrochi John , Jasseh Momodou , Mackenzie Grant , Castro Marcia C.
Published: February 2015

Objectives

To describe the spatial pattern in under‐5 mortality rates in the Basse Health and Demographic Surveillance System (BHDSS) and to test for associations between under‐5 deaths and biodemographic and socio‐economic risk factors.

Methods

Using data on child survival from 2007 to 2011 in the BHDSS, we mapped under‐5 mortality by km2. We tested for spatial clustering of high or low death rates using Kulldorff's spatial scan statistic. Associations between child death and a variety of biodemographic and socio‐economic factors were assessed with Cox proportional hazards models, and deviance residuals from the best‐fitting model were tested for spatial clustering.

Results

The overall death rate among children under 5 was 0.0195 deaths per child‐year. We found two spatial clusters of high death rates and one spatial cluster of low death rates; children in the two high clusters died at a rate of 0.0264 and 0.0292 deaths per child‐year, while in the low cluster, the rate was 0.0144 deaths per child‐year. We also found that children born to Fula mothers experienced, on average, a higher hazard of death, whereas children born in the households in the upper two quintiles of asset ownership experienced, on average, a lower hazard of death. After accounting for the spatial distribution of biodemographic and socio‐economic characteristics, we found no residual spatial pattern in child mortality risk.

Conclusion

This study demonstrates that significant inequality in under‐5 death rates can occur within a relatively small area (1100 km2). Risks of under‐5 mortality were associated with mother's ethnicity and household wealth. If high mortality clusters persist, then equity concerns may require additional public health efforts in those areas.
The NdhV subunit is required to stabilize the chloroplast NADH dehydrogenase‐like complex in Arabidopsis
Authors: Fan Xiangyuan , Zhang Jiao , Li Wenjing , Peng Lianwei
Published: February 2015

The chloroplast NADH dehydrogenase‐like (NDH) complex is involved in cyclic electron transport around photosystem I (PSI) and chlororespiration. Although the NDH complex was discovered more than 20 years ago, its low abundance and fragile nature render it recalcitrant to analysis, and it is thought that some of its subunits remain to be identified. Here, we identified the NDH subunit NdhV that readily disassociates from the NDH complex in the presence of detergent, salt and alkaline solutions. The Arabidopsis ndhv mutant is partially defective in the accumulation of NDH subcomplex A (SubA) and SubE, resulting in impaired NDH activity. NdhV was mainly detected in the wild‐type thylakoid membrane, and its accumulation in thylakoids strictly depended on the presence of the NDH complex. Quantitative immunoblot analysis revealed that NdhV and NdhN occur at close to equimolar concentrations. Furthermore, several NDH subunits were co‐immunopurified with NdhV using a combination of chemical crosslinking and an affinity chromatography assay. These data indicate that NdhV is an intrinsic subunit of NDH. We found that NdhV did not directly affect NDH activity, but that NDH SubA and SubE were more rapidly degraded in ndhv than in the wild type under high‐light treatment. We propose that NdhV is an NDH subunit that stabilizes this complex, especially under high‐light conditions.
Molecular lineage diversity and inter‐oceanic biogeographical history inHiatella(Mollusca, Bivalvia)
Authors: Laakkonen Hanna M. , Strelkov Petr , Väinölä Risto
Published: February 2015

Hiatellais one of the most widespread marine bivalve genera, occurring in diverse habitats from the temperate to polar latitudes in both hemispheres, and in fossil strata since almost 150 Myr ago. Despite variation in some biological and morphological traits, characters to resolve the current systematic structure consistently across the range of the genus are not known: all samples are often referred to a single species,Hiatella arctica(L.). Exploring the systematics ofHiatellausing partial sequences of three genes (mitochondrialCOI,and the nuclearANTand28S rRNA), we find high diversity of deep lineages (11–22%p‐distance inCOI), and identify at least 13 distinct taxa both by heuristic criteria (congruence of the nuclear and mtDNAdata) and by coalescence‐based analyses. At several localities, two or three of these cryptic species were found in sympatry. In the framework of previous fossil evidence and of hypotheses of paleoceanographical connections, scenarios of the phylogeny and biogeographical history of the identified species at a range of different time scales are outlined. The distinction between the main North Pacific and North AtlanticHiatellaclades and systematic diversification within each of them seem to have followed a Miocene trans‐Panamanian invasion. Apart from such earlier intra‐basin diversification, the data suggest that three successive counter‐invasions from the Pacific to the Atlantic via the Arctic Ocean route have later contributed to the current North AtlanticHiatelladiversity. These invasions probably took place in connection with (i) the Great Trans‐Arctic Biotic Interchange in the Pliocene, (ii) the last interglacial periodc. 120 kya and (iii) the Holocene, postdating the last glaciation. This sequence of trans‐Arctic invasions is largely analogous to that hypothesized for some other boreal‐arctic bivalves.
On an exotic Lagrangian torus in
Authors: Wu Weiwei
Published: February 2015

We find a non-displaceable Lagrangian torus fiber in a semi-toric system which is superheavy with respect to a certain symplectic quasi-state. The proof employs both 4-dimensional techniques and those from symplectic field theory. In particular, our result implies Lagrangian$\mathbb{R}P^{2}$is not a stem in$\mathbb{C}P^{2}$, answering a question of Entov and Polterovich.
Radiologic findings of idiopathic granulomatous mastitis
Authors: Yildiz Seyma , Aralasmak Ayse , Kadioglu Huseyin , Toprak Huseyin , Yetis Huseyin , Gucin Zuhal , Kocakoc Ercan
Published: February 2015

Aim: To describe the radiological findings of idiopathic granulomatous mastitis (IGM). Material and methods: Radio- logic findings of 30 women with histopathological diagnosis of IGM were retrospectively evaluated. All had breast feeding history. All the patients had ultrasonography (US), with 12 of them having additional Doppler US. Of 30 patients, 11 had mam- mography (MG) and 5 MRI. Results: US showed multiple irregular hypoechoic masses and collection areas with tubular con- nections in 25 of 30. The collection area with low-level internal echoes but without tubular connections, suggesting an abscess were seen in 2 of 30 (6.6%); a hypoechoic mass with an indistinct border in 2 of 30 (6.6%); multiple milimetric hypoechoic nodular masses in 1 of 30 (3.3%). On MG, normal findings were noted in 5 (45.4%); focal asymmetric density in 4 (36.4%), parenchymal distortion in 1 (9%) and diffuse asymmetric opacity with trabecular thickening in 1 (9%) of 30 patients. On MRI, segmental T2 hyperintensity with contrast-enhancement on T1 were seen in 4 of 5 (80%). An enhancing T2 hypointense mass with irregular margin was present in 1 of 5 (20%). Time-signal intensity curve of lesions showed slow enhancement in 1 and moderate in 4 of 5 patients. Conclusions: In IGM, MG findings were nonspecific. In US, multiple irregular hypoechoic masses and collections with tubular connections with fingerlike aspects, and fistulae formation to the skin in patients with breastfeed- ing history suggested IGM rather than carcinoma. Due to the limited number of patients, no conclusion was reached regarding MRI of IGM.
Analysis of protein coatings on gold nanoparticles by XPS and liquid-based particle sizing techniques
Authors: Belsey Natalie A. , Shard Alex G. , Minelli Caterina
Published: February 2015

The precise use of nanoparticles in technological applications requires control over their surface properties. This implies the ability to quantitatively describe, for example, molecular coatings in terms of their thickness, areal mass, or number of molecules. Here, the authors describe two different approaches to the measurement of these parameters by using gold nanoparticles ranging in diameter from 10 to 80 nm and coated with three different proteins: immunoglobulin G, bovine serum albumin, and a peptide. One approach utilizes ultraviolet–visible spectroscopy, dynamic light scattering, and differential centrifugal sedimentation to measure the protein shell refractive indices and thicknesses, from which the number of molecules in the protein shell can be derived. The other approach employs x-ray photoelectron spectroscopy to measure the thickness of the dry molecular coatings and also to derive the number of molecules in the protein shell. The authors demonstrate that the two approaches, although very different, produce consistent measurement results. This finding is important to extend the quantitative analysis of nanoparticle molecular coatings to a wide range of materials.
Promising method toward realization of ultra-low-cost silicon microrod array with nanotip
Authors: Yaghootkar Bahareh , Kahrizi Mojtaba
Published: February 2015

A low-cost two-step method for fabrication of silicon microrod array with nanotip on a low-doped p-type substrate was demonstrated. The two-step process involved anisotropic and electrochemical etching of single crystalline silicon samples. The silicon surface was first textured using anisotropic etching to generate the pyramid-shaped structure on the surface and was further followed by electrochemical anodic etching to create silicon microrod arrays. The vertical silicon microrod arrays are a direct product of the anodization stage, where the shape of the pyramid structures was altered and transformed into free-standing microrods. The effects of several parameters including the time, the pyramid size uniformity, and HF concentration on the final products were studied. It was observed that the diameters of the pyramids were decreased as the anodic etching time was extended to 10 min. Beyond 10 min, anodic etching did not cause any further diameter change. Experiments revealed that in order to realize silicon microrods, the size of the pyramids was required to be greater than the space charge region width. An optimal range of HF concentration, where the silicon microrods can be obtained was determined.
Atlantic and Pacific multidecadal oscillations and Northern Hemisphere temperatures
Authors: Steinman Byron A. , Mann Michael E. , Miller Sonya K.
Published: February 2015

Is the end of the warming hiatus nigh?

Which recent climate changes have been forced by greenhouse gas emissions, and which have been natural fluctuations of the climate system? Steinman
et al.
combined observational data and a large collection of climate models to assess the Northern Hemisphere climate over the past 150 years (see the Perspective by Booth). At various points in time, the Pacific Decadal Oscillation and the Atlantic Multidecadal Oscillation have played particularly large roles in producing temperature trends. Their effects have combined to cause the apparent pause in warming at the beginning of the 21st century, known as the warming “hiatus.” This pause is projected to end in the near future as temperatures resume their upward climb.

Science
, this issue p.
988
; see also p.
952
Evolution of sexual traits influencing vectorial capacity in anopheline mosquitoes
Authors: Mitchell Sara N. , Kakani Evdoxia G. , South Adam , Howell Paul I. , Waterhouse Robert M. , Catteruccia Flaminia
Published: February 2015

Mating plugs promote malaria parasites

Males of some of the malaria-transmitting mosquitoes “plug” females after copulation to stop interloping males from mating. The mating plug also delivers a steroid hormone into the female uterus. This hormone pulse promotes egg production and stimulates egg laying. It also curbs the mosquitoes' immune responses, which allows parasites such as malaria to develop unhindered. Mitchell
et al.
discovered that plugs are a recent evolutionary acquisition (see the Perspective by Alonzo). South American anopheline mosquitoes lack these plugs altogether, whereas African and Indian species have complex plugs replete with hormones. It is unlikely to be a coincidence that the most elaborate mosquito plugs are also found in regions where malaria transmission rates are highest.

Science
, this issue p.
985
; see also p.
948