bluuebunny/crossref_metadata_2025 huggingface dataset:
The Invisibility of Disability: Using Dance to Shake from Bioethics the Idea of ‘Broken Bodies’
Authors: Harmon Shawn H.E.
Published: December 2014

Complex social and ethical problems are often most effectively solved by engaging them at the messy and uncomfortable intersections of disciplines and practices, a notion that grounds the InVisible Difference project, which seeks to extend thinking and alter practice around the making, status, ownership, and value of work by contemporary dance choreographers by examining choreographic work through the lenses of law, bioethics, dance scholarship, and the practice of dance by differently‐abled dancers. This article offers a critical thesis on how bioethics has come to occupy a marginal and marginalizing role in questions about the differently‐abled body. In doing so, it has rendered the disabled community largely invisible to and in bioethics. It then defends the claim that bioethics – as a social undertaking pursued collaboratively by individuals from different disciplines – must take much better notice of the body and the embodied individual if it is to better achieve its ends, which include constructing a moral and just society. Finally, this article considers how the arts, and specifically dance (and here dance by differently‐abled dancers), provides us with rich evidence about the body and our ability to respond positively to normally ‘othered’ bodies. It concludes that greater attention to empirical evidence like that being generated in InVisible Difference will help to expand the reach and significance of bioethics, and thereby its relevance to (and consciousness of) important questions about the status of bodies and bodily differences, which must be considered as central to its ambitions.
Cancer‐associated fibroblast‐targeted strategy enhances antitumor immune responses in dendritic cell‐based vaccine
Authors: Ohshio Yasuhiko , Teramoto Koji , Hanaoka Jun , Tezuka Noriaki , Itoh Yasushi , Asai Tohru , Daigo Yataro , Ogasawara Kazumasa
Published: December 2014

Given the close interaction between tumor cells and stromal cells in the tumor microenvironment (TME), TME‐targeted strategies would be promising for developing integrated cancer immunotherapy. Cancer‐associated fibroblasts (CAFs) are the dominant stromal component, playing critical roles in generation of the pro‐tumorigenic TME. We focused on the immunosuppressive trait of CAFs, and systematically explored the alteration of tumor‐associated immune responses by CAF‐targeted therapy. C57BL/6 mice s.c. bearing syngeneic E.G7 lymphoma, LLC1 Lewis lung cancer, or B16F1 melanoma were treated with an anti‐fibrotic agent, tranilast, to inhibit CAF function. The infiltration of immune suppressor cell types, including regulatory T cells and myeloid‐derived suppressor cells, in the TME was effectively decreased through reduction of stromal cell‐derived factor‐1, prostaglandin E2, and transforming growth factor‐β. In tumor‐draining lymph nodes, these immune suppressor cell types were significantly decreased, leading to activation of tumor‐associated antigen‐specific CD8+ T cells. In addition, CAF‐targeted therapy synergistically enhanced multiple types of systemic antitumor immune responses such as the cytotoxic CD8+ T cell response, natural killer activity, and antitumor humoral immunity in combination with dendritic cell‐based vaccines; however, the suppressive effect on tumor growth was not observed in tumor‐bearing SCID mice. These data indicate that systemic antitumor immune responses by various immunologic cell types are required to bring out the efficacy of CAF‐targeted therapy, and these effects are enhanced when combined with effector‐stimulatory immunotherapy such as dendritic cell‐based vaccines. Our mouse model provides a novel rationale with TME‐targeted strategy for the development of cell‐based cancer immunotherapy.
Pathogenesis of nasal polyposis
Authors: Hulse K. E. , Stevens W. W. , Tan B. K. , Schleimer R. P.
Published: December 2014

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition that affects a large proportion of the population world‐wide and is associated with high cost of management and significant morbidity. Yet, there is a lack of population‐based epidemiologic studies using current definitions of CRSwNP, and the mechanisms that drive pathogenesis in this disease remain unclear. In this review, we summarize the current evidence for the plethora of factors that likely contribute to CRSwNP pathogenesis. Defects in the innate function of the airway epithelial barrier, including diminished expression of antimicrobial products and loss of barrier integrity, combined with colonization by fungi and bacteria likely play a critical role in the development of chronic inflammation in CRSwNP. This chronic inflammation is characterized by elevated expression of many key inflammatory cytokines and chemokines, including IL‐5, thymic stromal lymphopoietin and CCL11, that help to initiate and perpetuate this chronic inflammatory response. Together, these factors likely combine to drive the influx of a variety of immune cells, including eosinophils, mast cells, group 2 innate lymphoid cells and lymphocytes, which participate in the chronic inflammatory response within the nasal polyps. Importantly, however, future studies are needed to demonstrate the necessity and sufficiency of these potential drivers of disease in CRSwNP. In addition to the development of new tools and models to aid mechanistic studies, the field of CRSwNP research also needs the type of robust epidemiologic data that has served the asthma community so well. Given the high prevalence, costs and morbidity, there is a great need for continued research into CRS that could facilitate the development of novel therapeutic strategies to improve treatment for patients who suffer from this disease.
Short‐term effect of intravitreal ranibizumab on intraocular concentrations of vascular endothelial growth factor‐A and pigment epithelium‐derived factor in neovascular glaucoma
Authors: Wang Jia Wei , Zhou Min Wen , Zhang Xiulan , Huang Wen Bin , Gao Xin Bo , Wang Wei , Chen Shida , Zhang Xin Yu , Ding Xiao Yan , Jonas Jost B
Published: December 2014

Background

This study aims to evaluate concentrations of pigment epithelium‐derived factor (PEDF) and vascular endothelial growth factor (VEGF)‐A in aqueous of patients with neovascular glaucoma prior to, and shortly after, an intravitreal ranibizumab injection.

Design

Interventional comparative study.

Participants

The study included patients undergoing an intravitreal ranibizumab injection about one week before anti‐glaucomatous surgery (study group) or who underwent routine cataract surgery (control group).

Methods

Aqueous and blood samples were collected at the occasions of intravitreal injections, anti‐glaucomatous surgery or cataract surgery. They were analysed by enzyme‐linked immunosorbent assay.

Main Outcome Measures

Concentrations of PEDF and VEGF‐A in aqueous.

Results

At baseline, concentrations VEGF‐A (3698 ± 2105 pg/mL vs. 233 ± 98 pg/mL) and PEDF (18.9 ± 11.9 ug/mL vs. 2.2 ± 0.6 ug/mL) were higher (P < 0.001) in the study group (n = 20 patients) than control group (n = 20 patients). The VEGF‐A/PEDF concentration ratio was higher in the study group (396 ± 554 vs. 110 ± 49; P = 0.02). One week after the ranibizumab injection, iris neovascularization had completely regressed in 17 (85%) eyes, and VEGF‐A concentration decreased significantly (P < 0.001) to 184 ± 130 pg/mL. The PEDF concentration remained unchanged (19 ± 12 ug/mL). The VEGF‐A/PEDF concentration ratio decreased to 13.2 ± 13.6. Plasma concentrations of VEGF‐A and PEDF did not differ significantly between both groups (P = 0.65 and P = 0.15, respectively) nor were they significantly correlated with the aqueous concentrations (all P > 0.15).

Conclusions

Aqueous concentrations of VEGF‐A and PEDF were significantly elevated in eyes with neovascular glaucoma. Within one week after intravitreal injection of ranibizumab, VEGF‐A concentration decreased to subnormal levels, while the PEDF concentration remained unchanged and the VEGF‐A/PEDF ratio decreased.
Influence of osteoporosis on the osteocyte density of human mandibular bone samples: a controlled histological human study
Authors: Oliveira Pablo S. , Rodrigues José A. , Shibli Jamil A. , Piattelli Adriano , Iezzi Giovanna , Perrotti Vittoria
Published: December 2014

Objectives

Osteocytes have emerged as key regulators of skeletal and mineral homeostasis. The number of these cells could be influenced by the presence of osteoporosis and osteopenia. Hence, the aim this study was to evaluate the osteocyte density in patients with osteopenia, and in patients with osteoporosis treated with bisphosphonates.

Materials and methods

Thirty‐nine patients were selected for this study and divided into three groups: (A) nine healthy patients (control), (B) 15 patients with osteopenia, and (C) 15 patients with osteoporosis. During the surgical insertion of dental implants in the lower jaw, bone samples were retrieved and processed for histological analysis of osteocyte density, measured as number of osteocytes/bone tissue area (μm2).

Results

Patients with osteopenia showed statistically higher values of osteocyte density than patients with osteoporosis (P < 0.05) No significant differences were detected between osteopenia and osteoporosis subjects vs. healthy patients (P > 0.05).

Conclusions

Bone metabolism diseases (osteoporosis and osteopenia) do not seem to influence the osteocyte density; this could be due to the administration of bisphosphonates in patients with osteoporosis. This information could play a fundamental role in the diagnosis and treatment of patients in a postmenopausal stage.
Evaluation of quality of life and function at 1 year after transanal endoscopic microsurgery
Authors: Hompes R. , Ashraf S. Q. , Gosselink M. P. , van Dongen K. W. , Mortensen N. J. , Lindsey I. , Cunningham C.
Published: December 2014

Aim

Transanal endoscopic microsurgery (TEM) enables organ preservation after rectal tumour surgery. Its application is being expanded using adjuvant and neoadjuvant treatments. Our objective was to evaluate the changes over time in anorectal function, urinary symptoms and quality of life (QoL) in patients who had TEM surgery for a rectal tumour.

Method

Between September 2009 and October 2012, a consecutive series of 102 patients underwent TEM at a single institution. Patients were asked to fill out standardized questionnaires at baseline and then at 6, 12, 26 and 52 weeks after surgery. The QoL among these patients was assessed using one generic (EQ‐5D) and two disease‐specific [European Organization for Research and Treatment of Cancer (EORTC) QLQ‐C30 and QLQ‐CR29] questionnaires. Anorectal and urinary symptoms were studied using the COlo‐REctal Functional Outcome (COREFO) and the International Prostate Symptom Score (I‐PSS) questionnaires, respectively.

Results

The response rate was 90% (92/102 patients). Postoperative complications occurred in 14% (13/92) of patients. The general QoL (as assessed using the EQ‐5D) was lower 6 and 12 weeks after TEM compared with baseline QoL (P < 0.05) but returned towards baseline after 26 weeks. Anorectal function (determined using the COREFO) was worse 6 weeks postoperatively (P < 0.01) but had normalized by 12 weeks. Urinary function (determined using the I‐PSS) was not affected at any time point after surgery. The total COREFO score and the American Society of Anesthesiologists (ASA) score were correlated with the deterioration in QoL.

Conclusion

The study demonstrates that TEM has a temporary and reversible impact on QoL and anorectal function. Intensive interrogation of QoL and function using appropriate questionnaires will help to define the role of organ‐preserving surgery for rectal cancer before and after chemoradiotherapy.
Plant lectins, from ancient sugar‐binding proteins to emerging anti‐cancer drugs in apoptosis and autophagy
Authors: Jiang Q.‐L. , Zhang S. , Tian M. , Zhang S.‐Y. , Xie T. , Chen D.‐Y. , Chen Y.‐J. , He J. , Liu J. , Ouyang L. , Jiang X.
Published: December 2014

Ubiquitously distributed in different plant species, plant lectins are highly diverse carbohydrate‐binding proteins of non‐immune origin. They have interesting pharmacological activities and currently are of great interest to thousands of people working on biomedical research in cancer‐related problems. It has been widely accepted that plant lectins affect both apoptosis and autophagy by modulating representative signalling pathways involved in Bcl‐2 family, caspase family, p53, PI3K/Akt, ERK, BNIP3, Ras‐Raf and ATG families, in cancer. Plant lectins may have a role as potential new anti‐tumour agents in cancer drug discovery. Thus, here we summarize these findings on pathway‐ involved plant lectins, to provide a comprehensive perspective for further elucidating their potential role as novel anti‐cancer drugs, with respect to both apoptosis and autophagy in cancer pathogenesis, and future therapy.
Trunk control in children with cerebral palsy: where are we now?
Authors: Desloovere Kaat , Heyrman Lieve
Published: December 2014

This commentary is on the original article by Curtis et al. on pages 351–357 of this issue.
Treatment of young patients with HNF1A mutations (HNF1A–MODY)
Authors: Raile K. , Schober E. , Konrad K. , Thon A. , Grulich‐Henn J. , Meissner T. , Wölfle J. , Scheuing N. , Holl R. W. ,   the DPV Initiative the German BMBF Competence Network Diabetes Mellitus
Published: December 2014

Aim

Children and adolescents with a molecular diagnosis of HNF1A–MODY should be treated with oral sulfonylurea according to current International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines.

Methods

We surveyed the German–Austrian DPV database of 50 043 people and included 114 patients with a confirmed molecular–genetic diagnosis of HNF1A mutation and diabetes onset at below age 18 years. We analysed hypoglycaemic episodes, metabolic control (HbA1c) and other clinical variables according to treatment groups.

Results

People with HNF1A–MODY were included and analysed according to treatment with insulin alone (n = 34), sulfonylurea (n = 30), meglitinides (n = 22) or lifestyle (n = 28). In those receiving any drug treatment (n = 86), severe hypoglycaemia did not occur with meglitinide and was highest (at 3.6 events per 100 patient‐years) with insulin. HbA1c was highest with insulin treatment (insulin = 58 mmol/mol, 7.5%; sulfonylurea = 55 mmol/mol, 7.2%; meglitinides = 52 mmol/mol, 6.9%; P = 0.008), whereas weight (BMI SD score), serum lipids and blood pressure were not different.

Conclusions

Of note, 40% of people with HNF1A–MODY and medical treatment were receiving insulin alone and thus were not being treated in line with up‐to‐date International Society for Pediatric and Adolescent Diabetes/International Diabetes Federation guidelines, despite insulin treatment being associated with worse metabolic control and the risk of hypoglycaemia. The unlicensed use of oral drugs in patients below age 18 years and adherence by both doctors and patients to the initial insulin treatment might contribute to this finding.
Development and validation of a cost–utility model for Type 1 diabetes mellitus
Authors: Wolowacz S. , Pearson I. , Shannon P. , Chubb B. , Gundgaard J. , Davies M. , Briggs A.
Published: December 2014

Aims

To develop a health economic model to evaluate the cost‐effectiveness of new interventions for Type 1 diabetes mellitus by their effects on long‐term complications (measured through mean HbA1c) while capturing the impact of treatment on hypoglycaemic events.

Methods

Through a systematic review, we identified complications associated with Type 1 diabetes mellitus and data describing the long‐term incidence of these complications. An individual patient simulation model was developed and included the following complications: cardiovascular disease, peripheral neuropathy, microalbuminuria, end‐stage renal disease, proliferative retinopathy, ketoacidosis, cataract, hypoglycemia and adverse birth outcomes. Risk equations were developed from published cumulative incidence data and hazard ratios for the effect of HbA1c, age and duration of diabetes. We validated the model by comparing model predictions with observed outcomes from studies used to build the model (internal validation) and from other published data (external validation). We performed illustrative analyses for typical patient cohorts and a hypothetical intervention.

Results

Model predictions were within 2% of expected values in the internal validation and within 8% of observed values in the external validation (percentages represent absolute differences in the cumulative incidence).

Conclusions

The model utilized high‐quality, recent data specific to people with Type 1 diabetes mellitus. In the model validation, results deviated less than 8% from expected values.
Severe Left Atrioventricular Valve Regurgitation Due to Discontinuity between the Leaflets of the Aortic and Left Atrioventricular Valves in a Patient with Endocardial Cushion Defect: A Rare Case Report
Authors: Nabati Maryam , Habibi Valiolla , Soleimani Aria , Shokri Mojtaba
Published: December 2014

Discontinuities between the leaflets of the aortic and left atrioventricular valves are uncommon congenital malformations. The anomaly may be discovered during surgery without preoperative diagnosis. It represents a spectrum of anomalies that result from interruption of the normal development of the endocardial cushions during the fetal life. We describe a rare case of Down syndrome with transient complete atrioventricular block and discontinuity between the leaflets of the aortic and left atrioventricular valves without intervening fibrous band, leading to separation and detachment between them. It caused severe eccentric jet of regurgitation originated from left ventricular outflow tract and base of anterior leaflet of left atrioventricular valve into the left atrium. He underwent cardiopulmonary bypass, and the defect between left atrioventricular valve and aortic annuli was sewn. Permanent epicardial pacing was inserted during cardiac surgery. To the best of our knowledge, such a case has not been previously reported in the literature.
Connectivity conservation priorities for individual patches evaluated in the present landscape: how durable and effective are they in the long term?
Authors: Rubio Lidón , Bodin Örjan , Brotons Lluís , Saura Santiago
Published: December 2014

One of the most widespread approaches for setting spatially‐explicit priorities for connectivity conservation consists in evaluating the effects of the individual removal of each habitat patch (one at a time) from the landscape. It however remains unknown the degree to which such priorities are valid and reliable in the longer term, as subsequent habitat losses and other disruptions accumulate in the landscape. We compared the patch prioritizations and estimated connectivity losses resulting from individual patch removals and from a more exhaustive assessment accounting for the potentially synergistic impacts of multiple habitat losses by testing all possible combinations of patch removals. Habitat availability (reachability) metrics and metapopulation capacity were calculated in purposefully simulated landscapes and in habitat distribution data for three bird species (NE Spain). We found that 1) individual patch removals allowed identifying areas of low contribution to connectivity that remained so after subsequent network modifications, 2) the most important patches identified through individual removals often did not coincide with those patches whose removal would actually be most detrimental after multiple habitat losses. However, these differences were smaller for the habitat reachability metrics, as well as for very mobile species that were largely insensitive to habitat spatial arrangement. If many patch losses over time are likely, it might be a more robust and fruitful conservation strategy for managers to pinpoint those patches that, with a low negative impact on connectivity, can be converted to other land uses, instead of trying to elucidate through individual patch removals which subset of protected patches would be the most effective for conserving as much connectivity as possible in the long term. Individual patch removals provide useful but non‐permanent guidelines that may need to be reassessed when substantial landscape modifications occur, which requires dynamic strategies for connectivity conservation in the face of global change.
Effects of three endophytic entomopathogens on sweet sorghum and on the larvae of the stalk borer Sesamia nonagrioides
Authors: Mantzoukas Spiridon , Chondrogiannis Christos , Grammatikopoulos George
Published: December 2014

Various endophytic fungi of native plants and crops are important entomopathogens. The objective of this study was to investigate the entomopathogenic action of Beauveria bassiana (Balsamo) Vuillemin, Metarhizium robertsii (Metchnikoff) Sorokin, and Isaria fumosorosea (Wize) Brown & Smith (all Ascomycota: Hypocreales) against larvae of Sesamia nonagrioides (Lefebvre) (Lepidoptera: Noctuidae) artificially introduced into Sorghum bicolor L. (Moench) (Poaceae) plants under natural environmental conditions. Sorghum bicolor is an economically important crop cultivated for grain, fiber, forage, and lately for biofuel, and S. nonagrioides is its main pest in Mediterranean areas. Young sorghum plants were inoculated with the entomopathogens by spraying in the field. Plant water status, chlorophyll concentration, photosynthesis, and transpiration were not affected. Thirty days after endophyte establishment, plants were infested with fourth instars of S. nonagrioides. The endophytes prevented 50–70% of larvae from entering stalks. Larval mortality was 70–100% and tunnel lengths were reduced by 60–87%. Larval infestation resulted in reduced electron transport capacity and net photosynthetic rate, which was ameliorated in the presence of I. fumosorosea and reversed by B. bassiana and M. robertsii. The growth of sorghum was unaffected in all treatments during the experimental period. Beauveria bassiana and M. robertsii can protect sweet sorghum from damage induced by S. nonagrioides under natural environmental conditions without affecting plant physiology and growth.
Soil organic and inorganic carbon and stable carbon isotopes in the Yanqi Basin of northwestern China
Authors: Wang J. P. , Wang X. J. , Zhang J. , Zhao C. Y.
Published: December 2014

Soil organic carbon (SOC) and soil inorganic carbon (SIC) are important reservoirs of carbon in terrestrial ecosystems. Assessments of both SOC and SIC are lacking in arid regions. We carried out a survey in central Xinjiang, the Yanqi Basin, to evaluate the dynamics of SOC and SIC. Twenty‐one soil profiles were sampled from three land types: desert, shrub and agricultural soils. We determined SOC and SIC and the stable carbon isotope compositions (δ13C). Our data showed a decrease with depth for SOC in all soil profiles but an increase for SIC except in the desert soils. Both SOC and SIC stocks (over the 0–30‐cm depth) were least in the desert soils (1.0 ± 0.3 and 4.0 ± 0.8 kg C m−2 for SOC and SIC, respectively) but greatest in the agricultural soils (4.6 ± 0.6 and 11.0 ± 2.0 kg C m−2 for SOC and SIC, respectively). Total soil carbon stocks at 0–100 cm were 11.6 ± 4.8, 45.1 ± 10.4 and 51.2 ± 5.6 kg C m−2 in the desert soils, shrub soils and agricultural soils, respectively. On average, SIC accounted for more than 80% of the total carbon in this region. There were no significant differences in δ13C of SOC between land‐use types. In contrast, the δ13C of SIC was different: desert soils (−0.6‰) > shrub soils (−2.2‰) > agricultural soils (−3.4‰). The depleted 13C in SIC in the agricultural soils indicates enhancement of pedogenic carbonate by cropping. Our study suggests that converting shrub land to agricultural land in arid regions may lead to an increase not only in SOC stock, but also in SIC stock.
Relationships between quartz weathering and soil type (Entisol, Inceptisol and Alfisol) in Sierra Nevada (southeast Spain)
Authors: Martín‐García J. M. , Márquez R. , Delgado G. , Sánchez‐Marañón M. , Delgado R.
Published: December 2014

Quartz was studied in a soil development sequence of Entisol‐Inceptisol‐Alfisol in a Mediterranean mountain climate on a metamorphic quartz‐rich substrate, using scanning electron microscopy (SEM), energy dispersive X‐ray (EDX) and backscattered electron (BSE) and electron microprobes (EMP), with fine sand (250–50 µm) as the selected particle‐size fraction. The quartz in the soil is inherited mainly from the parent rock. However, a study of the surface characteristics of the quartz grains and measurement of non‐Si elements (Al3+, Ti4+, Fe3+, Na+, K+, Mg2+ and Ca2+), both near‐edge and in the centre of grains, showed that the quartz is altered substantially in the progression parent rock < Entisol < Inceptisol < Alfisol, and in the A, AC and Bt horizons rather than in the C horizon. In all profiles and horizons the content of non‐Si elements was greater in the near‐edge zones than in the centre of the grain. This pedochemical process thus operates mainly at the surface of the grain and results in a variety of pits, fissures and other corrosion features (hole or corrosion gulf, opening of inter‐granular surfaces, areal alteration, smoothing of edges of conchoidal fractures, and deepening of incisions of conchoidal fractures). Estimation of the W index, which assesses the intensity of the weathering process from the size and density of the etch pits, revealed that many of the quartz grains had alterations somewhat similar to the quartzes of tropical soils. This study casts doubt on the paradigm of quartz inalterability in soils of little to medium pedological change in temperate zones.
Glomalin‐related soil protein in French temperate forest soils: interference in the Bradford assay caused by co‐extracted humic substances
Authors: Jorge‐Araújo P. , Quiquampoix H. , Matumoto‐Pintro P. T. , Staunton S.
Published: December 2014

Thermostable soil protein, known as glomalin, is an important component of soil carbon stocks. Thought to originate from endomycorrhizal fungi, Glomales, this operationally‐defined fraction of soil organic matter contains proteins of diverse origin as well as non‐protein material, including humic substances. Accumulation results from the balance between production/release and subsequent degradation. Quantification of the protein is subject to uncertainty because of the co‐extraction of other components that interfere with the Bradford assay. We studied 10 topsoils from French temperate forests, taken from the national forest monitoring network (Renecofor). Two fractions were extracted, easily extractable (EE) at neutral pH and total extractable (T) at pH 8. Protein was quantified with the colorimetric Bradford method, either by direct calibration using bovine serum albumin (BSA) or by extrapolation of the standard addition plot of BSA. Solubilized organic matter was characterized by using absorbance at 465 and 665 nm and by three‐dimensional fluorescence excitation‐emission spectroscopy. Neither soil properties nor forest cover influenced glomalin‐related soil protein (GRSP) content. Direct assay gave the GRSPEE to be about 1 g kg−1 soil, and GRSPT in the range 3–10 g kg−1, accounting for about 2% of soil organic carbon and about 15% of soil nitrogen. Standard addition plots indicated a two to sixfold under‐estimation of protein in total extracts, caused by negative interference with the Bradford assay. The GRSPEE was correlated significantly with both estimates of GRSPT. Under‐estimation of GRSPT by direct assay was not related to the E4:E6 ratio but was correlated significantly with the intensity of absorbance at either 460 or 660 nm and with one of the fluorescence peaks. We conclude that GRSPEE is not necessarily more recent than GRSPT and that both fractions may be probes of protein content, but that absolute contents may be under‐estimated because of co‐extracted humic substances.
Pathogenic EFHC1 mutations are tolerated in healthy individuals dependent on reported ancestry
Authors: Subaran Ryan L. , Conte Juliette M. , Stewart William C. L. , Greenberg David A.
Published: December 2014

Objective

Screening for specific coding mutations in the EFHC1 gene has been proposed as a means of assessing susceptibility to juvenile myoclonic epilepsy (JME). To clarify the role of these mutations, especially those reported to be highly penetrant, we sought to measure the frequency of exonic EFHC1 mutations across multiple population samples.

Methods

To find and test variants of large effect, we sequenced all EFHC1 exons in 23 JME and 23 non‐JME idiopathic generalized epilepsy (IGE) Hispanic patients, and 60 matched controls. We also genotyped specific EFHC1 variants in IGE cases and controls from multiple ethnic backgrounds, including 17 African American IGE patients, with 24 matched controls, and 92 Caucasian JME patients with 103 matched controls. These variants are reported to be pathogenic, but are also found among unphenotyped individuals in public databases. All subjects were from the New York City metro area and all controls were required to have no family history of seizures.

Results

We found the reportedly pathogenic EFHC1 P77T‐R221H (rs149055334‐rs79761183) JME haplotype in one Hispanic control and in two African American controls. Public databases also show that the EFHC1 P77T‐R221H JME haplotype is present in unphenotyped West African ancestry populations, and we show that it can be found at appreciable frequency in healthy individuals with no family history of epilepsy. We also found a novel splice‐site mutation in a single Hispanic JME patient, the effect of which is unknown.

Significance

Our findings raise questions about the effect of reportedly pathogenic EFHC1 mutations on JME. One intriguing possibility is that some EFHC1 mutations may be pathogenic only when introduced into specific genetic backgrounds. By focusing on data from multiple populations, including the understudied Hispanic and Black/African American populations, our study highlights that for complex traits like JME, the body of evidence necessary to infer causality is high.
The Right Stuff: A NASA Technology–Based New Venture and the Search for Markets on Earth
Authors: Terjesen Siri
Published: December 2014

This case follows entrepreneur David Belaga's journey in identifying, licensing, and commercializing a National Aeronautics and Space Administration patent for a novel beverage that helps astronauts and athletes stay hydrated. The case reviews the entrepreneurial processes of identifying an opportunity, licensing the technology, creating a supplier network, assembling a board of advisors, developing a social media strategy, and fine–tuning the marketing mix. The case ends with Belaga's major challenge of reaching new customer markets.
Noncoding RNAs as epigenetic mediators of skeletal muscle regeneration
Authors: Sohi Gurjeev , Dilworth Francis Jeffrey
Published: December 2014

Skeletal muscle regeneration is a well‐characterized biological process in which resident adult stem cells must undertake a series of cell‐fate decisions to ensure efficient repair of the damaged muscle fibers while also maintaining the stem cell niche. Satellite cells, the main stem cell contributing to the repaired muscle fiber, are maintained in a quiescent state in healthy muscle. Upon injury, the satellite cells become activated, and proliferate to expand the muscle progenitor cell population before returning to the quiescent state or differentiating to become myofibers. Importantly, the determination of cell fate is controlled at the epigenetic level in response to environmental cues. In this review, we discuss our current understanding of the role played by noncoding RNAs (both miRNAs and long‐noncoding RNAs) in the epigenetic control of muscle regeneration.
Interactive creep–fatigue crack growth of 2024‐T3 Al sheets: selective transitional functions
Authors: Tang K. K. , Li S. H.
Published: December 2014

Interactive creep–fatigue on aeronautical materials has been of a great concern to engineers and researchers. There are still more fundamental issues to be addressed. In this regard, 2024‐T3 Al sheets are considered to study the transitional behaviours that incorporatematerial, loading and geometry effects in the interactive creep–fatigue process. A dual‐scale fatigue crack growth da/dN‐ΔS model that includes microscale, macroscale and large scales is proposed based on the volume energy density criterion. The model generates the transitionalised crack length (TCL) compared with the fictitious crack length (FCL) yielded from the da/dN‐ΔK model that is only restricted to monoscaling. Crossover points are observed across TCL and FCL curves. With stress amplitude being fixed, three levels of mean stress are employed to discuss the variational effects of transitional functions (TFs). Applied loading conditions have an appreciable effect on the fatigue life cycles of 2024‐T3 Al sheets. Variation of R ratios leads to the interactive creep–fatigue behaviour and further enforces the selective TFs in the inherent multiscaling process. TCLs and FCLs are compared with test data of the 2024‐T3 Al sheet. Rationality and superiority of the dual‐scale crack growth model are validated.
Local adaptation and embryonic plasticity affect antipredator traits in hatchling pond snails
Authors: Dalesman Sarah , Thomas Angharad , Rundle Simon D.
Published: December 2014

The biology of induced defences in very early life history stages is poorly understood in freshwater invertebrates, but may be equally, if not more, important than later stages in influencing population dynamics and survival. Here, we investigated how exposure of embryos of the pond snail Lymnaea stagnalis to predator kairomones altered traits associated with protection (crawl out behaviour and shell size) in hatchling snails. We also investigated whether levels of plasticity were influenced by habitat of origin by comparing reaction norms from sites with different levels of predation risk: three high risk (predatory fish present) and three low risk (predatory fish absent).

F2 embryos from snails from each population were exposed to kairomones from a predatory fish (Tinca tinca) or control conditions for their entire development up to the point of hatching. Their avoidance behaviour and size (spire height) were then measured 1 day and 7 days after hatching.

One day post‐hatching, levels of predator avoidance, primarily time spent at the water line, were significantly greater in high‐risk versus low‐risk populations; however, avoidance was also increased in hatchling snails exposed to predator cues as embryos, compared with those developing in control conditions. Snails exposed to predator cues during development were smaller, and there was a strong negative relationship between size and avoidance behaviour, suggesting a trade‐off or trait compensation between growth and behaviour.

At 7 days post‐hatching, a similar pattern in avoidance behaviour was found, with increased avoidance in snails from high‐risk habitats and in those exposed to predator kairomones during their development. The primary avoidance response switched to crawling above the waterline at 7 days post‐hatching. There was no significant difference in shell size between treatments, suggesting that predator‐exposed snails had exhibited ‘catch‐up’ growth. This enhanced investment in growth between 1 day and 7 days post‐hatching was positively correlated with elevated avoidance behaviour across treatment groups, demonstrating that snails switched to trait co‐specialisation of defence traits.

During the first few days post‐hatching, snails alter the type of avoidance behaviour and also the relationship between morphological and behavioural defence traits. The degree of expression of these defensive traits in hatchling snails is influenced by both their developmental environment and local adaptation to their predation habitat that may have large implications for survival.
Directionality of recent bird distribution shifts and climate change in Great Britain
Authors: Gillings Simon , Balmer Dawn E. , Fuller Robert J.
Published: December 2014

There is good evidence that species' distributions are shifting poleward in response to climate change and wide interest in the magnitude of such responses for scientific and conservation purposes. It has been suggested from the directions of climatic changes that species' distribution shifts may not be simply poleward, but this has been rarely tested with observed data. Here, we apply a novel approach to measuring range shifts on axes ranging through 360°, to recent data on the distributions of 122 species of British breeding birds during 1988–1991 and 2008–2011. Although previously documented poleward range shifts have continued, with an average 13.5 km shift northward, our analysis indicates this is an underestimate because it ignores common and larger shifts that occurred along axes oriented to the north‐west and north‐east. Trailing edges contracted from a broad range of southerly directions. Importantly, these results are derived from systematically collected data so confounding observer‐effort biases can be discounted. Analyses of climate for the same period show that whilst temperature trends should drive species along a north–north‐westerly trajectory, directional responses to precipitation will depend on both the time of year that is important for determining a species' distribution, and the location of the range margin. Directions of species' range centroid shift were not correlated with spatial trends in any single climate variable. We conclude that range shifts of British birds are multidirectional, individualistic and probably determined by species‐specific interactions of multiple climate factors. Climate change is predicted to lead to changes in community composition through variation in the rates that species' ranges shift; our results suggest communities could change further owing to constituent species shifting along different trajectories. We recommend more studies consider directionality in climate and range dynamics to produce more appropriate measures of observed and expected responses to climate change.
Snowpack, fire, and forest disturbance: interactions affect montane invasions by non‐native shrubs
Authors: Stevens Jens T. , Latimer Andrew M.
Published: December 2014

Montane regions worldwide have experienced relatively low plant invasion rates, a trend attributed to increased climatic severity, low rates of disturbance, and reduced propagule pressure relative to lowlands. Manipulative experiments at elevations above the invasive range of non‐native species can clarify the relative contributions of these mechanisms to montane invasion resistance, yet such experiments are rare. Furthermore, global climate change and land use changes are expected to cause decreases in snowpack and increases in disturbance by fire and forest thinning in montane forests. We examined the importance of these factors in limiting montane invasions using a field transplant experiment above the invasive range of two non‐native lowland shrubs, Scotch broom (Cytisus scoparius) and Spanish broom (Spartium junceum), in the rain–snow transition zone of the Sierra Nevada of California. We tested the effects of canopy closure, prescribed fire, and winter snow depth on demographic transitions of each species. Establishment of both species was most likely at intermediate levels of canopy disturbance, but at this intermediate canopy level, snow depth had negative effects on winter survival of seedlings. We used matrix population models to show that an 86% reduction in winter snowfall would cause a 2.8‐fold increase in population growth rates in Scotch broom and a 3.5‐fold increase in Spanish broom. Fall prescribed fire increased germination rates, but decreased overall population growth rates by reducing plant survival. However, at longer fire return intervals, population recovery between fires is likely to keep growth rates high, especially under low snowpack conditions. Many treatment combinations had positive growth rates despite being above the current invasive range, indicating that propagule pressure, disturbance, and climate can all strongly affect plant invasions in montane regions. We conclude that projected reductions in winter snowpack and increases in forest disturbance are likely to increase the risk of invasion from lower elevations.
Response of wheat growth, grain yield and water use to elevated CO2 under a Free‐Air CO2 Enrichment (FACE) experiment and modelling in a semi‐arid environment
Authors: O'Leary Garry J. , Christy Brendan , Nuttall James , Huth Neil , Cammarano Davide , Stöckle Claudio , Basso Bruno , Shcherbak Iurii , Fitzgerald Glenn , Luo Qunying , Farre‐Codina Immaculada , Palta Jairo , Asseng Senthold
Published: December 2014

The response of wheat crops to elevated CO2 (eCO2) was measured and modelled with the Australian Grains Free‐Air CO2 Enrichment experiment, located at Horsham, Australia. Treatments included CO2 by water, N and temperature. The location represents a semi‐arid environment with a seasonal VPD of around 0.5 kPa. Over 3 years, the observed mean biomass at anthesis and grain yield ranged from 4200 to 10 200 kg ha−1 and 1600 to 3900 kg ha−1, respectively, over various sowing times and irrigation regimes. The mean observed response to daytime eCO2 (from 365 to 550 μmol mol−1 CO2) was relatively consistent for biomass at stem elongation and at anthesis and LAI at anthesis and grain yield with 21%, 23%, 21% and 26%, respectively. Seasonal water use was decreased from 320 to 301 mm (P = 0.10) by eCO2, increasing water use efficiency for biomass and yield, 36% and 31%, respectively. The performance of six models (APSIM‐Wheat, APSIM‐Nwheat, CAT‐Wheat, CROPSYST, OLEARY‐CONNOR and SALUS) in simulating crop responses to eCO2 was similar and within or close to the experimental error for accumulated biomass, yield and water use response, despite some variations in early growth and LAI. The primary mechanism of biomass accumulation via radiation use efficiency (RUE) or transpiration efficiency (TE) was not critical to define the overall response to eCO2. However, under irrigation, the effect of late sowing on response to eCO2 to biomass accumulation at DC65 was substantial in the observed data (~40%), but the simulated response was smaller, ranging from 17% to 28%. Simulated response from all six models under no water or nitrogen stress showed similar response to eCO2 under irrigation, but the differences compared to the dryland treatment were small. Further experimental work on the interactive effects of eCO2, water and temperature is required to resolve these model discrepancies.
Effects of alkaloids from fungal endophytes in grass–Epichloëassociations on survival of the sorghum plant bug (Stenotus rubrovittatus)
Authors: Shiba Takuya , Arakawa Akira , Sugawara Koya
Published: December 2014

Epichloë(Neotyphodium) endophytes are symbiotic fungi in association with gramineous plants and produce a range of alkaloids that enhance the resistance of host plants to insect pests.N‐formylloline, one of theEpichloë‐produced alkaloids, is known to be toxic to some insects but not to mammals. Therefore,Epichloë‐infected grasses with highN‐formylloline concentrations are expected to reduce the population of some insect pests in meadows. To assess the adverse effects ofN‐formylloline on the survival of the sorghum plant bug (Stenotus rubrovittatus) known as a major pest, artificial feeding ofN‐formylloline through feeding sachets was carried out.N‐formylloline reduced the survival ofS. rubrovittatus, even at 50 ppm, which was considerably lower than the concentrations in mostEpichloë‐infected grasses. The results suggest thatN‐formylloline inEpichloë‐infected grasses can reduce the population ofS. rubrovittatusin meadows.
Late acceleration of glomerular filtration rate decline is a risk for hemodialysis catheter use in patients with established nephrology chronic kidney disease care
Authors: Chin Andrew I. , Nguyen Tuan A. , Dinesh Kumar P. , Morfin José A.
Published: December 2014

Chronic kidney disease (CKD) patients with established nephrology care have a high rate of tunneled dialysis catheters (TDC) as first vascular access when transitioning to hemodialysis (HD). We sought to identify factors associated with this problem. Patients who started HD and had prior CKD care within our renal clinic were categorized according to access type at incident HD. Clinical factors, all estimated glomerular filtration rates (eGFR), renal clinic attendance records, hospital admissions in the 6 months preceding HD start, and patient participation in predialysis education course were analyzed. Three hundred thirty‐eight patients initiated HD, 107 received pre‐HD CKD care within our clinics. Seventy patients started with a TDC. All groups started HD at similar eGFR values. The trajectory of eGFR decline in the 6 months prior to HD start was significantly more rapid in the TDC group. Patients in the TDC group had more acute health events in the prior 6 months. Multivariate modeling showed that failure to attend a predialysis education course and having a more rapid rate of eGFR decline in the 6 months prior to dialysis initiation were both associated with TDC use. Patients with CKD nephrology care who initiated HD with a TDC as first vascular access had a more rapid rate of decline in eGFR in the months preceding dialysis start and were less likely to have attended our predialysis education course. This appears to correspond with the observed increased number of emergency and hospital visits in the 6 months prior to end‐stage renal disease.
Development of a patient‐centred, patient‐reported outcome measure (PROM) for post‐stroke cognitive rehabilitation: qualitative interviews with stroke survivors to inform design and content
Authors: Patchick Emma L. , Horne Maria , Woodward‐Nutt Kate , Vail Andy , Bowen Audrey
Published: December 2014

Background

Improving cognition is service users' top research priority for life after stroke, and future research should include outcomes that they deem important. Patient perspectives on outcomes are collected using patient‐reported outcome measures (PROMs). There is currently no patient‐centred PROM specific for cognitive rehabilitation trials.

Objective

Inform PROM development by exploring stroke survivor perspectives on the important, measurable impacts of persisting post‐stroke cognitive problems.

Design

Qualitative semi‐structured interviews in participants' homes.

Participants

Purposive sample of 16 cognitively impaired stroke survivors at least six months post‐stroke.

Methods

Interviews used a schedule and communication aids developed through patient consultation. Interviews were transcribed verbatim with non‐verbal communication recorded using field notes. Data were analysed using a framework approach to find commonalities to shape the focus and content of an outcome measure.

Results

Participants identified important impacts of their ‘invisible’ cognitive problems, outside of other stroke‐related impairments. Cognitive problems exacerbated emotional issues and vice versa. Changes in self‐identity and social participation were prominent. Impact was not spoken about in terms of frequency but rather in terms of the negative affect associated with problems; terms like ‘bothered’ and ‘frustration’ were often used.

Conclusions

The results support the development of a PROM specifically designed to address the impact of cognitive problems. It should:

include items addressing a comprehensive range of cognitive skills;

ask questions about mood, self‐identity and social participation;

use accessible wording that respondents understand and endorse;

measure impact rather than frequency; and

explore perceived impact on carers.