bluuebunny/crossref_metadata_2025 huggingface dataset:
The deep end of the metabolite pool: influences on epigenetic regulatory mechanisms in cancer
Authors: Nordgren Kendra K. , Skildum Andrew J.
Published: December 2014

Background

Epigenetic control of gene expression is mediated by cytosine methylation/demethylation and histone modifications including methylation, acetylation and glycosylation. The epigenetic programme is corrupted in cancer cells to maintain a pattern of gene expression that leads to their de‐differentiated, rapidly proliferating phenotype. Enzymes responsible for modifying histones and cytosine are sensitive to the cellular metabolite pool and can be activated by an increase in their substrates or inhibited by an increase in their products or competitors for substrate binding.

Methods

This review is based on publications identified on PubMed using a literature search of cytosine methylation, histone methylation, acetylation and glycosylation.

Results

In cancer, changes in glycolytic enzymes lead to increased production of serine, increasing the pool of S‐adenosylmethionine (the major methyl donor for methylation reactions) and UDP‐N‐acetylglucosamine (a substrate for O‐linked glycosylation of histones and cytosine methyltransferases). Mutations in tricarboxylic acid cycle enzymes lead to accumulation of fumarate, succinate and hydroxyglutarate, all of which inhibit demethylation of cytosine and histones. In contrast, proline catabolism produces α‐ketoglutarate and reactive oxygen, both of which promote the activity of enzymes that remove methyl groups from cytosine and histones, and the key enzyme in proline catabolism acts as a tumour suppressor.

Conclusions

Our emerging understanding of how the epigenetic profiles are metabolically reprogrammed in cancer cells will lead to novel diagnostic and therapeutic targets for treatment of patients.
Inspiration vs. perspiration in economic development of the Former Soviet Union and China (ca. 1920–2010)
Authors: van Leeuwen Bas , Didenko Dmitry , Földvári Péter
Published: December 2014

Here, we discuss the role of both perspiration factors (physical and human capital) and inspiration factors (Total Factor Productivity) in the economic development of the Former Soviet Union area (FSU) and China, ca. 1920–2010. Using a newly created dataset, we find that during the Socialist central‐planning period, economic growth in both countries was largely driven by physical capital accumulation. This finding follows logically from the development policies in place at that time. During their transition periods, (i.e., starting from the late 1970s in China and the late 1980s in theFSU), China managed to keep technical inefficiency of production factors in check, largely by massively increasing its human capital, thereby lowering the physical‐to‐human capital ratio. In contrast, theFSUaccomplished a similar outcome largely through reducing its stock of physical capital. As a result, although there was little difference in technical efficiency between these two economies, China's emphasis on human capital formation made it easier for this country to improve its general productivity and to increaseper capitagrowth. This changed in the late 1990s and early 2000s, when theFSUbegan to recover economically, regaining its 1990 levels of output and productivity.
A genetic comparison of sympatric anadromous and resident Atlantic salmon
Authors: Adams Blair K. , Cote David , Hutchings Jeffrey A.
Published: December 2014

Many studies have identified the importance of local adaptation in Atlantic salmon (Salmo salar) and the strong genetic differences that exist between allopatric or parapatric resident and anadromous populations. However, as truly sympatric migratory phenotypes of Atlantic salmon have not been studied, it remains unclear whether distinct genotypes previously associated with life history differences are maintained through reproductive isolation and subsequent genetic drift or through natural selection induced by different life history requirements. In this study, sympatric anadromous and resident Atlantic salmon were sampled from three Newfoundland (Canada) watersheds to evaluate the genetic divergence of these life history forms. Eight microsatellite loci were used to quantify genetic variation within and among populations. Metrics of genetic differentiation (exact tests for population differentiation, pairwise θ values) provide no evidence of genetic differentiation between some sympatric anadromous and resident phenotypes within a system with no history of segregation. In the remaining two watersheds, the observed differentiation appears to be a consequence of historical segregation rather than life history form. Nonetheless, these differences have been maintained in contemporary times for several generations. At broader spatial scales, resident salmon were more genetically divergent from one another than anadromous life history forms and were more closely related to anadromous salmon from within their watershed than to resident salmon from other watersheds. The study indicates that both life history forms can be maintained within a single population, but that sympatric populations of different life histories can maintain genetic differences for at least several generations after being reconnected.
Management of basidiomycete root‐ and stem‐rot diseases in oil palm, rubber and tropical hardwood plantation crops
Authors: Mohammed C. L. , Rimbawanto A. , Page D. E.
Published: December 2014

Basal stem‐rot and root‐rot diseases caused by basidiomycete fungal pathogens are naturally and widely occurring in a large range of hosts. However, they significantly reduce the productivity of several economically important plantation‐crop industries in tropical countries. Oil palm, rubber, acacias and eucalypts are all susceptible to basidiomycete rot pathogens to varying degrees and there is no absolute disease resistance. The causal pathogens are persistent as they remain present in wood or crop debris even in the absence of living members of the host species. Disease build‐up is often rapid and can reach economically unacceptable levels in the absence of interventions to contain the disease. This study reviews the biology and detection of root‐rot disease in oil palm, rubber and hardwood crops with a specific focus on management strategies undertaken in South‐East Asia. The diseases caused by basidiomycete rot pathogens in this region are intractable and require an integrated approach to disease management, as it is unlikely that any one control strategy will succeed. In contrast, there has been significant success in reducing losses from basidiomycete rot from pathogens in the northern hemisphere, especially with Heterobasidion annosum sensu lato in forest trees, research being often supported by the establishment of long‐term trials required to understand the origins and types of disease. In the tropics, progress has been more fragmented due to the low level of research funding, the problems involved with managing long‐term research trials in the tropics, the confidentiality requirements of competitive industries and the lack of literature available in the public arena. This review collates a large body of information from disparate and often obscure sources for oil palm, rubber, acacias and eucalypts, tropical plantation crops that face similar types of stem‐ and root‐rot disease problems. Lessons to be learned from the successes and failures of various management strategies with each type of crop are examined.
Signs and identification of fungal root‐rot pathogens in tropical Eucalyptus pellita plantations
Authors: Agustini L. , Francis A. , Glen M. , Indrayadi H. , Mohammed C. L.
Published: December 2014

This study describes and identifies the fungi associated with root‐rot disease in Eucalyptus pellita, associated anecdotally with a species of Phellinus. Macro‐ and microscopic morphological observations and DNA analysis were used to identify sporocarps and fungal cultures growing from symptomatic root samples. Investigation of 12 sites in Central Sumatra revealed that red root‐rot disease caused by species of Ganoderma (most commonly Ganoderma philippii) was as prevalent as root disease caused by Phellinus noxius. The study also detected the presence of several potential fungal agents of root rot at any one site. Fungal signs such as absence/presence of sporocarps were a poor indicator of root‐rot incidence in stands. Instead, fungal isolation from infected roots was essential to obtain accurate identification of active pathogens.
Familial thrombotic risk based on the genetic background of Protein C Deficiency in a Portuguese Study
Authors: Fidalgo Teresa , Martinho Patrícia , Salvado Ramon , Manco Licínio , Oliveira Ana C. , Pinto Catarina S. , Gonçalves Elsa , Marques Dalila , Sevivas Teresa , Martins Natália , Ribeiro Maria Letícia
Published: December 2014

Introduction

Inherited protein C (PC) deficiency is a well‐known risk factor for venous thrombosis (VT). Plasma PC levels are reliable in moderate to severe deficiencies; however, in mildly deficient individuals, the levels may overlap with those considered normal. Genetic studies of PROC, which encodes PC, could help identify carriers; genome‐wide association studies (GWAS) have shown that approximately 50% of phenotypic variation in PC deficiency is caused by the cumulative effects of mutations in several other loci, namely in the PROCR.

Patients and methods

With the main objective of determining the genotype/phenotype correlation in 59 Portuguese individuals from 26 unrelated families with history of thrombosis and repeatedly low/borderline PC plasma levels, we conducted a molecular study by direct sequencing of PROC; PROC promoter haplotypes and PROCR c.4600A>G polymorphism (rs867186), which are known to influence plasma PC concentrations, were also screened.

Results

Twelve different PROC mutations were identified, one of them not previously reported, p.Cys105Arg. The mutation types and locations as well as haplotype combinations correlated with the phenotypic severity. The most frequent mutation, p.Arg199X, correlated with the CGTC haplotype and was identified in nine families containing patients with higher numbers of VT episodes. This mutation in homozygous individuals for the CGTC haplotype is a significant risk factor for VT in Portuguese.

Conclusion

These genetic family studies allowed the identification of the unknown carriers and individuals at a higher thrombotic risk within each family, thus permitting the evaluation of the need for prophylactic measures, particularly in at‐risk situations.
Soil, food security and human health: a review
Authors: Oliver M. A. , Gregory P. J.
Published: December 2014

Direct effects of soil or its constituents on human health are through its ingestion, inhalation or absorption. The soil contains many infectious organisms that may enter the human body through these pathways, but it also provides organisms on which our earliest antibiotics are based. Indirect effects of soil arise from the quantity and quality of food that humans consume. Trace elements can have both beneficial and toxic effects on humans, especially where the range for optimal intake is narrow. We focus on four trace elements (iodine, iron, selenium and zinc) whose deficiencies have substantial effects on human health. As the world's population increases issues of food security become more pressing, as does the need to sustain soil fertility and minimize its degradation. Lack of adequate food and food of poor nutritional quality lead to differing degrees of under‐nutrition, which in turn causes ill health. Soil and land are finite resources and agricultural land is under severe competition from other uses. Relationships between soil and health are often difficult to extricate because of the many confounding factors present. Nevertheless, recent scientific understanding of soil processes and factors that affect human health are enabling greater insight into the effects of soil on our health. Multidisciplinary research that includes soil science, agronomy, agricultural sustainability, toxicology, epidemiology and the medical sciences will facilitate the discovery of new antibiotics, a greater understanding of how materials added to soil used for food production affect health and deciphering of the complex relationships between soil and human health.
Quantifying dung carbon incorporation by earthworms in pasture soils
Authors: Schon N. L. , Mackay A. D. , Gray R. A. , Dodd M. B. , van Koten C.
Published: December 2014

The effect of different earthworm functional groups on the incorporation of maize (C4 plant) dung into a soil (C3 organic matter background) sown with ryegrass (C3 plant) was explored by using differences in the carbon (C) isotope ratios (12C and 13C) between plant and soil samples in a field mesocosm study. The abundance of earthworms increased with dung inputs, reaching over 4000 earthworms per m2, presumably because of the increased food resources used. The amount of dung C incorporated into the soil profile in the presence of earthworms was dependent on the amount of organic matter deposited on the soil surface (925–4620 g C m−2) and reached rates of 1200 g C m−2 annually in the treatment receiving repeat dung applications. Dung incorporation was largely concentrated in the surface 0–75 mm, although small amounts of dung‐derived C were observed to a depth of 300 mm. This was especially so in the presence of anecic earthworms, equating to an extra 70 g C m−2 annually for the 150–300 mm depth increment. It is important to note, in calculating C incorporation rates from earthworms, that only 10–20% of the soil surface in grazed pastures is covered by dung. After 444 days, less than 32% of the applied dung was detected within the upper 300 mm of the soil profile. This study emphasized the need for all three earthworm functional groups to be present within the soil in order to maximize the amount of surface dung that could be incorporated into soil organic matter.
Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial‐onset seizures: Results of a phase III, double‐blind, randomized, placebo‐controlled trial
Authors: Sperling Michael R. , Abou‐Khalil Bassel , Harvey Jay , Rogin Joanne B. , Biraben Arnaud , Galimberti Carlo A. , Kowacs Pedro A. , Hong Seung Bong , Cheng Hailong , Blum David , Nunes Teresa , Soares‐da‐Silva Patrício ,   the 304 Study Team
Published: December 2014

Objective

To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial‐onset seizures.

Methods

This randomized, placebo‐controlled, double‐blind, parallel‐group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial‐onset seizures despite treatment with 1–2 antiepileptic drugs (AEDs). After an 8‐week baseline period, patients were randomized to once‐daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2‐week titration period, patients received ESL 800 or 1,200 mg once‐daily for 12 weeks. Seizure data were captured and documented using event‐entry or daily entry diaries.

Results

Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment‐emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia.

Significance

Adjunctive ESL 1,200 mg once‐daily was more efficacious than placebo in adult patients with refractory partial‐onset seizures. The once‐daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by diary format used.
Ultrafast fluorescence upconversion technique and its applications to proteins
Authors: Chosrowjan Haik , Taniguchi Seiji , Tanaka Fumio
Published: December 2014

The basic principles and main characteristics of the ultrafast time‐resolved fluorescence upconversion technique (conventional and space‐resolved), including requirements for nonlinear crystals, mixing spectral bandwidth, acceptance angle, etc., are presented. Applications to flavoproteins [wild‐type (WT) FMN‐binding protein and its W32Y, W32A, E13R, E13K, E13Q and E13T mutants] and photoresponsive proteins [WT photoactive yellow protein and its R52Q mutant in solution and as single crystals] are demonstrated. For flavoproteins, investigations elucidating the effects of ionic charges on ultrafast electron transfer (ET) dynamics are summarized. It is shown that replacement of the ionic amino acid Glu13 and the resulting modification of the electrostatic charge distribution in the protein chromphore‐binding pocket substantially alters the ultrafast fluorescence quenching dynamics and ET rate in FMN‐binding protein. It is concluded that, together with donor–acceptor distances, electrostatic interactions between ionic photoproducts and other ionic groups in the proteins are important factors influencing the ET rates. In WT photoactive yellow protein and the R52Q mutant, ultrafast photoisomerization dynamics of the chromophore (deprotonated trans‐p‐coumaric acid) in liquid and crystal phases are investigated. It is shown that the primary dynamics in solution and single‐crystal phases are quite similar; hence, the photocycle dynamics and structural differences observed at longer time scales arise mostly from the structural restraints imposed by the crystal lattice rigidity versus the flexibility in solution.
Improving the accuracy of recombinant protein production through integration of bioinformatics, statistical and mass spectrometry methodologies
Authors: Ragionieri Lapo , Vitorino Rui , Frommlet Joerg , Oliveira José L. , Gaspar Paulo , Ribas de Pouplana Lluís , Santos Manuel A. Silva , Moura Gabriela Ribeiro
Published: December 2014

Heterologous protein production is a key technology for biotechnological, health sciences and many other research fields. Various approaches have been developed for its optimization, but the research emphasis has been on optimization of protein yield rather than protein quality. In this study, we have established a workflow for synthetic gene optimization for heterologous protein expression that combines bioinformatics, laboratory experiments, mass spectrometry and statistical analysis. Two gene primary structure analysis platforms, Anaconda and EuGene, and multivariate optimization methods were employed to re‐design the Plasmodium falciparum lysyl‐tRNA synthetase gene for optimal expression in Escherichia coli. Synthetic genes were expressed from common vectors, and amino acid mis‐incorporations in the expressed proteins were detected and quantified using mass spectrometry. The association between the identified amino acid mis‐incorporations and 23 gene variables was then analysed. The synthetic genes yielded significantly higher levels of protein relative to the wild‐type gene, but 71 amino acid mis‐incorporation sites were observed along the whole protein and across the synthetic genes that were statistically associated with specific codons and protein secondary structures. The optimization method that led to production of the most accurate protein was based on a multivariate approach that combined variables that are known to influence mRNA translation.
Prostate hyperplasia caused by long‐term obesity is characterized by high deposition of extracellular matrix and increased content of MMP‐9 and VEGF
Authors: Silva Silas Amâncio , Gobbo Marina Guimarães , Pinto‐Fochi Maria Etelvina , Rafacho Alex , Taboga Sebastião Roberto , Almeida Eduardo Alves , Góes Rejane Maira , Ribeiro Daniele Lisboa
Published: December 2014

Recent studies have shown a positive association of cancer and obesity, but the morphological and molecular mechanisms involved in this relationship are still unknown. This study analysed the impact of long‐term obesity on rat prostate, focusing on stromal changes. Male adult Wistar rats were treated with high‐fat diet to induce obesity, while the control group received a balanced diet. After 30 weeks of feeding, the ventral prostate was analysed by immunohistochemistry for cell proliferation, smooth muscle α‐actin, vimentin, chondroitin sulphate and metalloproteinases (MMP‐2 and 9). The content of androgen receptor (AR), oestrogen receptors (ERs) and vascular endothelial growth factor (VEGF) was measured by Western blotting, and activity of catalase and Glutathione‐S‐Transferase (GST) were quantified by enzymatic assay. Long‐term obesity decreased testosterone plasma levels by 70% and resulted in stromal prostate hyperplasia, as evidenced by increased collagen fibres. Such stromal hyperplasia was associated with increased number of blood vessels and raised VEGF content, and increased expression of chondroitin sulphate, vimentin, α‐actin and MMP‐9. In spite of the high cell density in prostate, the proliferative activity was lower in the prostates of obese rats, indicating that hyperplasia was established during the early phases in this obesity model. AR levels increased significantly, whereas the ERα decreased in this group. Moreover, the levels of catalase and GST were changed considerably. These findings indicate that long‐term obesity, besides disturbing the antioxidant control, causes intense stromal remodelling and release of factors that create an environment that can promote proliferative disorders in the gland, culminating with diffuse hyperplasia.
Exogenous connexin43‐expressing autologous skeletal myoblasts ameliorate mechanical function and electrical activity of the rabbit heart after experimental infarction
Authors: Antanavičiūtė Ieva , Ereminienė Eglė , Vysockas Vaidas , Račkauskas Mindaugas , Skipskis Vilius , Rysevaitė Kristina , Treinys Rimantas , Benetis Rimantas , Jurevičius Jonas , Skeberdis Vytenis A.
Published: December 2014

Acute myocardial infarction is one of the major causes of mortality worldwide. For regeneration of the rabbit heart after experimentally induced infarction we used autologous skeletal myoblasts (SMs) due to their high proliferative potential, resistance to ischaemia and absence of immunological and ethical concerns. The cells were characterized with muscle‐specific and myogenic markers. Cell transplantation was performed by injection of cell suspension (0.5 ml) containing approximately 6 million myoblasts into the infarction zone. The animals were divided into four groups: (i) no injection; (ii) sham injected; (iii) injected with wild‐type SMs; and (iv) injected with SMs expressing connexin43 fused with green fluorescent protein (Cx43EGFP). Left ventricular ejection fraction (LVEF) was evaluated by 2D echocardiography in vivo before infarction, when myocardium has stabilized after infarction, and 3 months after infarction. Electrical activity in the healthy and infarction zones of the heart was examined ex vivo in Langendorff‐perfused hearts by optical mapping using di‐4‐ANEPPS, a potential sensitive fluorescent dye. We demonstrate that SMs in the coculture can couple electrically not only to abutted but also to remote acutely isolated allogenic cardiac myocytes through membranous tunnelling tubes. The beneficial effect of cellular therapy on LVEF and electrical activity was observed in the group of animals injected with Cx43EGFP‐expressing SMs. L‐type Ca2+ current amplitude was approximately fivefold smaller in the isolated SMs compared to healthy myocytes suggesting that limited recovery of LVEF may be related to inadequate expression or function of L‐type Ca2+ channels in transplanted differentiating SMs.
Effect of waxy flour blends on dough rheology and bread quality
Authors: Blake Laura H. , Jenner Colin F. , Barber Andrew R. , Gibson Robert A. , O'Neill Brian K. , Nguyen Q. Dzuy
Published: December 2014

Although much research has been conducted on wheat flour dough rheology, the principal focus has been the role of the protein fraction. Starch is the main component of flour and plays a key role in dough dynamic properties, particularly during heating. This study assesses the effect of two different waxy flours, a durum and a bread wheat, and their blends with commercial bakers' flour on dough rheology during heating with a concurrent investigation into baking performance. Both waxy flour blends produced similar effects on dough rheological behaviour despite differences in protein content, acting to delay gelatinisation and reduce storage modulus. The main effects in bread were to increase loaf expansion during baking and reduce loaf firmness. It is postulated these effects are largely water mediated, with the higher swelling ability of the waxy starch granules reducing overall water availability and driving complete gelatinisation to higher temperatures.
Contribution of influenza to acute exacerbations of chronic obstructive pulmonary disease in Kashmir, India, 2010–2012
Authors: Koul Parvaiz A. , Khan Umar H. , Asad Romana , Yousuf Rubaya , Broor Shobha , Lal Renu B. , Dawood Fatimah S.
Published: December 2014

We estimate the contribution of influenza to hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in Kashmir, India. Prospective surveillance for influenza among patients hospitalized with AECOPD was conducted at a tertiary care hospital. Patients had clinical data collected and nasal/throat swabs tested for influenza viruses. Outcomes among patients with and without influenza were compared with logistic regression adjusting for age and underlying conditions. During October 2010–September 2012, 498 patients hospitalized with AECOPD were enrolled, of whom 40 (8%) had received influenza vaccine. Forty (8%) had influenza; influenza virus detection peaked in winter (January–March). Patients with influenza were more likely to die during hospitalization (adjusted OR 3·4, CI 1·0–11·4) than those without.
Synthesis and Properties of Bi2Fe4O9 with FeCl2·6H2O Addition
Authors: Gao Kaige , Zhu Jiansheng , Gu Xiaomin , Xie Qiyun , Zhang Fengming , Wu Xiaoshan
Published: December 2014

Single‐phase Bi2Fe4O9 is synthesized successfully by the solid‐state reaction technique with FeCl2·6H2O additives. The two optical band gaps, and the iron ion's chemical valence state both decrease with the addition of FeCl2·6H2O, which may be attributed to the decrease in the split energy of iron 3d orbital.
Dielectric Properties of Ultra‐Low Sintering Temperature Al2O3–BBSZ Glass Composite
Authors: Chen Mei‐Yu , Juuti Jari , Hsi Chi‐Shiung , Chia Chih‐Ta , Jantunen Heli
Published: December 2014

Ceramic composites of B2O3–Bi2O3–SiO2–ZnO (BBSZ) glass mixed with Al2O3 (10–50 vol%) were sintered at 450°C, and their microstructural and dielectric properties investigated. Dense structures were obtained when the Al2O3 content was lower than 30 vol%. Raman, XRD, and FESEM showed the existence of a secondary phase, Bi24Si2O40, in all samples. The dielectric properties of the composite with 30 vol% addition of Al2O3 showed good dielectric properties with εr of 14.8 and 20.8 and 32.5 at 100 kHz and 100 MHz and 1 GHz, respectively. The tanδ values at the same frequencies were 0.004 and 0.006 and 0.016. The results show that BBSZ glass with different amounts of Al2O3 exhibit widely applicable relative permittivity values and affordable loss and are thus promising candidates for ultra‐low sintering temperature applications.
Health Inequity in People with Intellectual Disabilities: From Evidence to Action Applying an Appreciative Inquiry Approach
Authors: Naaldenberg Jenneken , Banks Roger , Lennox Nick , Ouellette‐Kunz Hélène , Meijer Marijke , Lantman‐de Valk Henny van Schrojenstein
Published: December 2014

Background

The current understanding of health inequities in people with intellectual disabilities does not readily translate into improvements in health status or health care. To identify opportunities for action, the 2013 IASSIDD health SIRG conference organized ten intensive workshops.

Materials and methods

The workshops each addressed separate topics, a workshop of self advocated was included as well. Workshop reports were analyzed using a qualitative thematical analysis approach.

Results

A total of 134 participants attended the workshops. The analysis of the workshop reports resulted in three main themes: approach, know‐how and visibility and a pervasive theme, that of person‐centered support.

Conclusion

Everyone that can contribute to better care should be empowered and facilitated to do so, environments should be accessible and inclusive in nature. Sharing experiences, expertise and data sources within and outside intellectual disabilities care and research were mentioned as ways forward. Strong (policy) visions, felt urgency and shared responsibility are required.
Health and Disability: Partnerships in Health care
Authors: Tracy Jane , McDonald Rachael
Published: December 2014

Background

Despite awareness of the health inequalities experienced by people with intellectual disability, their health status remains poor. Inequalities in health outcomes are manifest in higher morbidity and rates of premature death. Contributing factors include the barriers encountered in accessing and receiving high‐quality health care.

Aims

This paper outlines health inequalities experienced by people with intellectual disability and focuses on the opportunities medical education provides to address these. Strategies to ensure that health professional education is inclusive of and relevant to people with disabilities are highlighted.

Conclusions

The barriers experienced by people with intellectual disabilities to the receipt of high‐quality health care include the attitudes, knowledge and skills of doctors. Improving medical education to ensure doctors are better equipped is one strategy to address these barriers. Improving health enhances quality of life, enables engagement and optimizes opportunities to participate in and contribute to the social and economic life of communities.

Accessible Abstract

People with intellectual disabilities sometimes find it difficult to get the healthcare they need to stay well.

Teaching student doctors about what people with disabilities want and need can help these students become better doctors.

Good doctors help people get well and stay healthy and active. When people feel well they can enjoy their lives and join in activities in their community.

This article talks about some of the things doctors need to learn, and some ways to teach them. People with disabilities have a very important role in teaching student doctors.
A one‐step rectification of sperm cell targeting ensures the success of double fertilization
Authors: Huang Jilei , Ju Yan , Wang Xiangfeng , Zhang Quan , Sodmergen  
Published: December 2014

Successful fertilization in animals depends on competition among millions of sperm cells, whereas double fertilization in flowering plants usually involves just one pollen tube releasing two immobile sperm cells. It is largely a mystery how the plant sperm cells fuse efficiently with their female targets within an embryo sac. We show that the initial positioning of sperm cells upon discharge from the pollen tube is usually inopportune for gamete fusions and that adjustment of sperm cell targeting occurs through release and re‐adhesion of one sperm cell, while the other connected sperm cell remains in stagnation. This enables proper adhesion of each sperm cell to a female gamete and coordinates the gamete fusions. Our findings reveal inner embryo sac dynamics that ensure the reproductive success of flowering plants and suggest a requirement for sperm cell differentiation as the basis of double fertilization.
Finite Optimal Penalties for False Advertising
Authors: Corts Kenneth S.
Published: December 2014

I consider a setting in which firms have unverifiable private information about their type, which corresponds to their probable product quality; firms can expend a learning cost in order to observe their quality; and the regulator can enforce false advertising penalties contingent only on verifiable realized quality. I show that it may be socially optimal for high type firms to signal their type through ‘speculative claims,’ rather than to learn and signal their quality. This implies that socially optimal false advertising penalties are finite, in contrast to the literature's common assumption of arbitrarily high false advertising penalties, and that the regulator optimally tolerates the existence of some false claims in equilibrium.
Changes in management and outcomes for children and adolescents with type 1 diabetes over the last 50 years
Authors: Fairchild Jan
Published: December 2014

Over the 50 years from 1964 to 2014, outcomes for children with type 1diabetes have improved significantly, because of both technological advancements and changes in management philosophy. For the child with type 1 diabetes in 2014, intensive management with multiple daily injections or insulin pump therapy and the support of a specialist multidisciplinary team is now standard care. The main treatment goal is no longer the avoidance of hypoglycaemia, but the minimisation of hyperglycaemia and glucose variability, thereby reducing the risk of microvascular complications. However, the inherent burden of care and diligence required by patients and families, if they are to maintain optimal diabetes control, have not changed and may even have increased. While the long sought‐after cure for diabetes remains elusive, artificial pancreas or closed‐loop systems hold the most promise for improving the burden of care in the near term for children and adolescents with type 1 diabetes.
Voter Turnout and Political Rents
Authors: ALDASHEV GANI
Published: December 2014

Is the decline in voter turnout an indicator of a worse health of a representative democracy? We build a simple probabilistic‐voting model with endogenous turnout to address this question. We find that a lower turnout caused by a higher cost of voting implies higher political rents. Contrarily, a lower turnout caused by a higher ideological mobility of voters or by a lower expressive benefit of voting implies lower political rents. If voters have a civic‐duty motive to vote that depends on the level of rents, multiple equilibria (a high‐rents low‐turnout and a low‐rents high‐turnout) arise.
Unemployment Compensation and the Allocation of Labor in Developing Countries
Authors: CHARLOT OLIVIER , MALHERBET FRANCK , ULUS MUSTAFA
Published: December 2014

This paper studies the effects of the introduction of unemployment compensation (UC) in countries characterized by pervasive informality. We provide a simple framework to analyze the impact of UC on the allocation of workers between formal and informal activities, as well as the allocation of workers between sectors featuring different incentives to go informal. We show that a reasonable amount of UC may reduce informality, while larger amounts of UC induce large disincentives to go formal because of the level of taxation involved. We also argue that the financing of UC should be part and parcel of a well‐conceived UC system. We show that UC finance based on payroll taxes is likely to entail an excess level of informality resulting from cross‐subsidies between heterogenous sectors. The introduction of a simple layoff tax meant to finance the UC system is then shown to reduce informality, hence highlighting how a well‐designed financing scheme may be used as a supplementary instrument to curb informality.
DIAGENESIS OF TIGHT‐GAS SANDSTONES IN THE LOWER CRETACEOUS DENGLOUKU FORMATION, SONGLIAO BASIN, NE CHINA: IMPLICATIONS FOR RESERVOIR QUALITY
Authors: Zhang Penghui , Lee Yong Il , Zhang Jinliang
Published: December 2014

Non‐marine tight‐gas sandstones have not been studied intensively in terms of diagenesis and reservoir‐quality evaluation. This paper investigates the sandstones in the Lower Cretaceous Denglouku Formation in the Songliao Basin, NE China, which comprise a tight reservoir for natural gas. Core samples of the sandstones were obtained from eight wells located in two gasfields and were described in terms of lithology and sedimentology with the aid of wireline log interpretation; other data included thin section petrography, and X‐ray diffraction analyses and scanning electron microscopy. The sandstones mainly comprise moderate‐ to well‐sorted, fine‐ to medium‐grained feldspathic litharenites deposited in braided fluvial to braid‐delta settings under warm, arid to semi‐arid climatic conditions. Diagenetic processes which have affected the sandstones include compaction and cementation by calcite, dolomite, ferroan calcite, quartz, chlorite and illite. Porosity characteristics of the sandstones are closely linked to depositional facies, and the sandstones can be divided on the basis of sediment textures and depositional facies into three groups which have distinctive diagenetic features. The best reservoirs are represented by relatively coarse‐grained sandstones deposited in braid‐delta mouth bars and distributary channels and braided fluvial channels; these sandstones have relatively high porosity (up to 5%) and contain large amounts of chlorite and illite pore‐lining cements but relatively minor carbonate cement. A reservoir quality prediction model is proposed and incorporates textural, depositional and diagenetic attributes. The model will help to identify sweet spots in non‐marine tight‐gas sandstones elsewhere, and will contribute to more effective field development.
Bodyweight and body condition score in rabbits on four different feeding regimes
Authors: Prebble J. L. , Shaw D. J. , Meredith A. L.
Published: December 2014

OBJECTIVES

The aim of this study was to assess the effects of four diet regimes (extruded diet with ad lib hay, muesli with ad lib hay, ad lib hay only, ad lib muesli only) on bodyweight and body condition score in rabbits.

METHODS

Thirty‐two Dutch rabbits were studied over 9 months. Bodyweight and body condition score were recorded weekly.

RESULTS

All groups gained weight with age, but relative to the ad lib hay only group (mean, 1 · 77 ± 0 · 13 kg), after 9 months rabbits in the ad lib muesli only group were 146% heavier (2 · 59 ± 0 · 32 kg); extruded diet with ad lib hay group 125% heavier (2 · 21 ± 0 · 10 kg); and muesli with ad lib hay group 123% heavier (2 · 18 ± 0 · 13 kg). Median body condition score of the ad lib muesli only group was obese (4 · 5) and was higher than that in both the extruded diet with ad lib hay and muesli with ad lib hay (median = 3 · 5) groups (P < 0 · 001). Both the extruded diet with ad lib hay and muesli with ad lib hay groups had above‐ideal body condition score despite having bodyweights within the breed standard range. The ad lib hay only group had a median body condition score of 3 (ideal). There was an overall positive correlation between body condition score and weight (qs = 0 · 814, P < 0 · 001).

CLINICAL SIGNIFICANCE

The feeding of muesli without hay should be avoided, to prevent obesity.
Nitrergic Function is Lost but Endothelial Function Is Preserved in the Corpus Cavernosum and Penile Resistance Arteries of Men After Radical Prostatectomy
Authors: Martínez-Salamanca Juan I. , La Fuente José M. , Fernández Argentina , Martínez-Salamanca Eduardo , Pepe-Cardoso Augusto J. , Carballido Joaquín , Angulo Javier
Published: December 2014

Introduction

Radical prostatectomy (RP) frequently results in erectile dysfunction (ED). It has been hypothesized that alterations of cavernosal tissue subsequent to RP contribute to ED but functional evaluation of the impact of RP on human erectile structures is lacking.

Aim

This study aims to evaluate endothelial function of human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) and neurogenic responses of HCC from patients with ED secondary to RP (ED-RP).

Methods

HCC strips and HPRA were obtained from organ donors without history of ED (No-ED) and patients with ED who were segregated depending on ED etiology: ED-RP or vasculogenic (ED-VASC). Functional evaluation of HCC and HPRA was performed in organ chambers and wire myographs, respectively. Histological evaluation of cavernosal tissue consisted of trichrome staining for fibrosis quantification and TUNEL assay for determination of apoptosis.

Main Outcome Measures

Endothelium-dependent and endothelium-independent relaxation, electrical field stimulation (EFS)-induced neurogenic contraction and relaxation, and cavernosal fibrosis and apoptosis.

Results

Endothelium-dependent relaxations were significantly impaired in HCC and HPRA from ED-VASC patients while these responses in ED-PR patients were not different to No-ED. Similarly, sildenafil-induced relaxations were reduced in HCC and HPRA from ED-VASC but were preserved in ED-RP. Adrenergic contractions induced by EFS in HCC were potentiated in both ED-RP and ED-VASC. EFS-induced nitrergic relaxation was significantly reduced in HCC from ED-VASC but was almost abolished in ED-RP. Fibrous tissue content and cavernosal apoptosis in HCC from ED-RP were not significantly different from No-ED.

Conclusions

Endothelial function and cavernosal sensitivity to phosphodiesterase type 5 inhibitors are preserved in erectile tissue from ED-RP while a marked imbalance in neurogenic modulation of cavernosal tone favoring adrenergic contractile responses over nitrergic relaxation is manifested. Fibrotic and apoptotic processes in cavernosal tissue are not specifically associated to ED-RP. These evidences could help to retarget therapeutic strategies in the management of ED after RP.
Effects of 8 weeks of CPAP on lipid‐based oxidative markers in obstructive sleep apnea: a randomized trial
Authors: Sivam Sheila , Witting Paul K. , Hoyos Camilla M. , Maw Aung M. , Yee Brendon J. , Grunstein Ronald R. , Phillips Craig L.
Published: December 2014

Dyslipidaemia and increased oxidative stress have been reported in severe obstructive sleep apnea, and both may be related to the development of cardiovascular disease. We have previously shown in a randomized crossover study in patients with moderate to severe obstructive sleep apnea that therapeutic continuous positive airway pressure treatment for 8 weeks improved postprandial triglycerides and total cholesterol when compared with sham continuous positive airway pressure. From this study we have now compared the effect of 8 weeks of therapeutic continuous positive airway pressure and sham continuous positive airway pressure on oxidative lipid damage and plasma lipophilic antioxidant levels. Unesterified cholesterol, esterified unsaturated fatty acids (cholesteryl linoleate: C18:2; and cholesteryl arachidonate: C20:4; the major unsaturated and oxidizable lipids in low‐density lipoproteins), their corresponding oxidized products [cholesteryl ester‐derived lipid hydroperoxides and hydroxides (CE‐O(O)H)] and antioxidant vitamin E were assessed at 20:30 hours before sleep, and at 06:00 and 08:30 hours after sleep. Amongst the 29 patients completing the study, three had incomplete or missing [CE‐O(O)H] data. The mean apnea –hypopnoea index, age and body mass index were 38 per hour, 49 years and 32 kg m−2, respectively. No differences in lipid‐based oxidative markers or lipophilic antioxidant levels were observed between the continuous positive airway pressure and sham continuous positive airway pressure arms at any of the three time‐points [unesterified cholesterol 0.01 mm, P > 0.05; cholesteryl linoleate: C18:2 0.05 mm, P > 0.05; cholesteryl arachidonate: C20:4 0.02 mm, P = 0.05; CE‐O(O)H 2.5 nm, P > 0.05; and lipid‐soluble antioxidant vitamin E 0.03 μm, P > 0.05]. In this study, accumulating CE‐O(O)H, a marker of lipid oxidation, does not appear to play a role in oxidative stress in obstructive sleep apnea.
Optimal management of patients with chronic hepatitis C and comorbidities
Authors: Boccaccio Vincenzo , Bruno Savino
Published: December 2014

Although HCV infection mainly induces liver injury, chronic disease is systemic. Moreover, host and viral factors, as well as comorbidities, may influence the chance of achieving a sustained virological response or disease outcome. Although there are sufficient data on the use of peg‐interferon and ribavirin in patients with comorbidities, there is very little data on first generation protease inhibitors, which include significant drug–drug interactions and have therefore been administered with caution in these patients. The availability of new, more effective direct acting antivirals should significantly change this scenario. All these issues are discussed in this review.
Treatment of hepatocellular carcinoma: beyond international guidelines
Authors: Colombo Massimo , Sangiovanni Angelo
Published: December 2014

The management of hepatocellular carcinoma (HCC) is decided according to evidence‐based recommendations generated by international societies: according to these recommendations, the tumour stage, as determined by the Barcelona clinical liver cancer (BCLC) score, divides patients into five prognostic categories, each with a distinct treatment indication. Radical therapies such as hepatic resection, orthotopic liver transplantation and percutaneous local ablation are strongly indicated in patients with very early and early stage tumours (BCLC O and A), a choice which mainly depends on a combination of tumour volume, status of underlying liver disease, the presence of comorbidities and the patient's age. Although radical therapies provide a survival rate of between 50% and 75% at year five in well selected patients, tumour recurrence is frequent following resection and ablation compared to transplantation (70% vs. 10% respectively), which has the additional advantage of preventing morbidity and mortality from portal hypertension. Generally, while radical therapies are contraindicated in patients with a large tumour burden, such as those with intermediate stage BCLC B, survival in the subset of these patients with well compensated cirrhosis may improve from 16 to 20 months, on average, following repeated treatments with transarterial chemoembolization (TACE). Survival may also improve in patients who are in poor condition or who do not respond to TACE and in those with an advanced HCC (BCLC C) following oral therapy with the multikinase inhibitor sorafenib. However, because most recommendations are based on uncontrolled studies and expert opinions rather than well designed, high powered randomized controlled trials, treatment criteria need to be adapted to special groups because real life cohorts do not match the selection criteria suggested by the guidelines. Indeed, up to one‐third of patients with early stage tumours who are unfit for radical therapy because of advanced age, the presence of significant comorbidities or a strategic location of the nodule, are forced to receive palliative care. BCLC A patients with moderate portal hypertension and certain BCLC B patients could still be eligible for hepatic resection if a chance for 50% survival at 5 years is still perceived as being cost‐effective by both the patient and caregivers.