bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective audit to evaluate the potential of the coronial system to increase solid organ donation
Authors: Twamley Huw , Haigh Andrew , Williment Claire , Hudson Cara , Whitney Julie , Neuberger James
Published: July 2016

Objectives

Anecdotal evidence suggests that organ donation from deceased donors referred to the Coroner/Procurator Fiscal (PF) could be increased if all followed best practice. The aim of this prospective audit was to establish how referrals affected organ donation and to develop evidence-based guidelines to ensure that organ donation can be facilitated safely without interfering in the Coroner/PF's investigative process.

Design

Prospective audit.

Setting

All acute National Health Service Hospitals in the UK where deceased organ donation was considered.

Participants

1437 deceased patients who met the eligibility criteria for organ donation and were referred to Coroner/PF.

Main outcome measures

Number of cases where permission for transplantation was given, number of organs where permission was refused and number of organs which might have been transplanted if all had followed best practice.

Results

Full permission for organ retrieval was given in 87% cases and partial permission in 9%. However, if full permission had been given where no autopsy was performed or restrictions seemed unjustified, up to 77 organs (22 lungs, 22 kidneys, 9 pancreases, 9 livers, 8 hearts and 7 small bowels) could have been available for transplant.

Conclusions

Coroners/PFs and their officers show strong support for transplantation but improvement in practice could result in a small but significant increase in life-saving and life-enhancing transplants.
Effectiveness of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES): a virtual non-inferiority trial
Authors: Reeves Barnaby C , Scott Lauren J , Taylor Jodi , Harding Simon P , Peto Tunde , Muldrew Alyson , Hogg Ruth E , Wordsworth Sarah , Mills Nicola , O'Reilly Dermot , Rogers Chris A , Chakravarthy Usha
Published: July 2016

Objectives

To compare the ability of ophthalmologists versus optometrists to correctly classify retinal lesions due to neovascular age-related macular degeneration (nAMD).

Design

Randomised balanced incomplete block trial. Optometrists in the community and ophthalmologists in the Hospital Eye Service classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomographic images. Participants' classifications were validated against experts' classifications (reference standard).

Setting

Internet-based application.

Participants

Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care.

Interventions

The trial emulated a conventional trial comparing optometrists' and ophthalmologists' decision-making, but vignettes, not patients, were assessed. Therefore, there were no interventions and the trial was virtual. Participants received training before assessing vignettes.

Main outcome measures

Primary outcome—correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes—potentially sight-threatening errors, judgements about specific lesion components and participants' confidence in their decisions.

Results

In total, 155 participants registered for the trial; 96 (48 in each group) completed all assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702/2016 (84.4%) and 1722/2016 (85.4%) correct classifications, respectively (OR 0.91, 95% CI 0.66 to 1.25; p=0.543). Optometrists' decision-making was non-inferior to ophthalmologists' with respect to the prespecified limit of 10% absolute difference (0.298 on the odds scale). Optometrists and ophthalmologists made similar numbers of sight-threatening errors (57/994 (5.7%) vs 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57; p=0.789). Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their classifications than optometrists.

Conclusions

Optometrists' ability to make nAMD retreatment decisions from vignettes is not inferior to ophthalmologists' ability. Shared care with optometrists monitoring quiescent nAMD lesions has the potential to reduce workload in hospitals.

Trial registration number

ISRCTN07479761; pre-results registration.
Lifestyle-related diseases following the evacuation after the Fukushima Daiichi nuclear power plant accident: a retrospective study of Kawauchi Village with long-term follow-up
Authors: Ebner Daniel K , Ohsawa Megumi , Igari Keiko , Harada Kouji H , Koizumi Akio
Published: July 2016

Objectives

Kawauchi Village lies 20 km west of the Fukushima Daiichi nuclear power plant. On 16 March 2011, evacuation was ordered due to the threat of radiological exposure, and was lifted in April 2012. In this study, we aimed to evaluate the predisaster and postdisaster health status of the Kawauchi Villagers, measured by routine yearly physical examinations.

Methods

We analysed the annual health examination data of residents of Kawauchi Village from 2008 to 2013, as available from the Japanese National Health Insurance system. Data from 2011 were not available due to the disaster. Since the health data included the same participants repeatedly from year to year, the sample was non-independent and generalised estimated equation modelling was used. A predisaster time period (2008–2010) was categorised for comparison with postdisaster 2012 and 2013. The outcome examined was the prevalence of metabolic disease, and was adjusted for confounding factors.

Results

Data for 20.6%–25.9% of the total residents were available in this period. In 2013, the prevalence of metabolic syndrome (from 17.0% to 25.2%, p<0.001), diabetes (from 11.3% to 17.0%, p<0.001), dyslipidaemia (from 43.2% to 56.7%, p<0.0001), hyperuricaemia (from 5.2% to 8.4%, p=0.006) and chronic kidney disease (from 16.1% to 26.7%, p<0.001) was found to be elevated significantly compared to predisaster years, while that of obesity or hypertension did not change.

Conclusions

The present follow-up study for Kawauchi Village revealed an increase in lifestyle-related disease following the March 2011 disaster and subsequent evacuation, and this trend still continues 2 years later.
A protocol for a randomised controlled trial investigating the effect of increasing Omega-3 index with krill oil supplementation on learning, cognition, behaviour and visual processing in typically developing adolescents
Authors: van der Wurff I S M , von Schacky C , Berge K , Kirschner P A , de Groot R H M
Published: July 2016

Introduction

The influence of n-3 long-chain polyunsaturated fatty acids (LCPUFA) supplementation on brain functioning is debated. Some studies have found positive effects on cognition in children with learning difficulties, elderly people with cognitive impairment and depression scores in depressed individuals. Other studies have found null or negative effects. Observational studies in adolescents have found positive associations between fish consumption (containing n-3 LCPUFAs) and academic achievement. However, intervention studies in typically developing adolescents are missing.

Objective

The goal of this study is to determine the influence of increasing Omega-3 Index on cognitive functioning, academic achievement and mental well-being of typically developing adolescents.

Methods and data analysis

Double-blind, randomised, placebo controlled intervention; 264 adolescents (age 13–15 years) attending lower general secondary education started daily supplementation of 400 mg eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA) in cohort I (n=130) and 800 mg EPA+DHA in cohort II (n=134) or a placebo for 52 weeks. Recruitment took place according to a low Omega-3 Index (<5%). The Omega-3 Index was monitored via a finger prick at baseline and after 3, 6 and 12 months. The supplement dose was adjusted after 3 months (placebo analogously) to reach an Omega-3 Index of 8–11%. At baseline, 6 and 12 months, a neuropsychological test battery, a number of questionnaires and a standardised math test (baseline and 12 months) were administered. School grades were collected. In a subsample, sleep quality and quantity data (n=64) and/or eye-tracking data (n=33) were collected.

Ethics and dissemination

Food2Learn is performed according to Good Clinical Practice. All data collected are linked to participant number only. The results will be disseminated on group level to participants and schools. The results will be presented at conferences and published in peer-reviewed journals. The study is approved by the Medical Ethical Committee of Atrium-Orbis-Zuyd Hospital and is registered at the Netherlands Trial Register (NTR4082).

Trial registration numbers

NTR4082 andNCT02240264; Pre-results.
Utilizing clinical pharmacists to improve delivery of evidence-based care for depression and anxiety in primary care
Authors: Locke Amanda , Kamo Norifumi
Published: July 2016

Access to mental health providers has become an increasingly common challenge for many patients with depression and anxiety disorders. Primary care providers often manage this gap in care and currently provide solo care without the assistance of other team members. In order to provide quality care that aligns with best practice, we developed a depression and anxiety disorder treatment pathway utilizing a multidisciplinary team based on each members' individual skill set, or skill-task alignment. The main change to treatment implemented by the pathway was the addition of a clinical pharmacist in the management of patient care. This pathway was trialed over five months targeting two adult primary care teams (approximately 34 physicians and Advanced Registered Nurse Practitioners [ARNPs]) while the other five teams continued with current practice standards. Post-implementation metrics indicated that clinical pharmacists successfully contacted 55% (406 of 738) of patients started on medication or who had a medication changed. Of these patients reached, 82 (20%) had an intervention completed. In addition, all physician leaders on the planning team (n=6) stated the new pathway was well received and delivered positive feedback from team members.
Different expression patterns ofLGALS1andLGALS3in polycythemia vera, essential thrombocythemia and primary myelofibrosis
Authors: Moura L G , Tognon R , Nunes N S , Rodrigues L Cataldi , Ferreira A F , Kashima S , Covas D T , Santana M , Souto E X , Perobelli L , Simões B P , Dias-Baruffi M , Castro F A
Published: July 2016

Despite all the knowledge, the cellular and molecular mechanisms involved in myeloproliferative neoplasm (MPN) pathophysiology remain unclear. Authors have shown galectin-1 (Gal-1) and 3 playing roles in tumour angiogenesis and fibrosis, which were correlated with poor prognosis in patients with MPN. In the present studyLGALS1andLGALS3were differently expressed between polycythemia vera, essential thrombocythemia (ET) and primary myelofibrosis (PMF) diseases. IncreasedLGALS3expression was associated with a negative JAK2 V617F status mutation in leucocytes from PMF but not in patients with ET without this mutation. However, a positive Janus kinase 2 (JAK2) V617F cell line established from patients with ET (SET-2 cells) when treated with JAK inhibitor presented high levels ofLGALS3.Additionally, highLGALS1expression was found in CD34+cells but not in leucocytes from patients with PMF, in absence of JAK2 V617F mutation, and also in SET-2 cells treated with JAK inhibitor. Thus, our findings indicate that differential expression ofLGALS1and/orLGALS3in patients with MPN is linked with JAK2 V617F status mutation in these diseases and state of cell differentiation.
Contribution of time-varying measures of health behaviours to socioeconomic inequalities in mortality: how to understand the underlying mechanisms?
Authors: Oude Groeniger Joost , van Lenthe Frank J
Published: July 2016

A higher prevalence of unhealthy behaviours in lower socioeconomic groups contributes to socioeconomic inequalities in mortality. Recent cohort studies suggest that the contribution of health behaviours to socioeconomic inequalities in mortality is larger when measured repeatedly over time (‘time-varying’) instead of once only (‘time-fixed’). Explanations for a larger contribution of health behaviours, however, are hardly discussed in the current literature, and appear to be more complex than a widening of inequalities in health behaviours over time alone. We describe the use of time-varying health behaviours to examine socioeconomic inequalities in mortality, systematically listing underlying mechanisms that may cause differences between time-varying and time-fixed models, and show that these mechanisms may be specific for each health behaviour. The use of time-varying health behaviours advances our understanding of the explanation of socioeconomic inequalities in mortality, but underlying mechanisms must be carefully examined.
The (re)-introduction of semiotics into medical education: on the works of Thure von Uexküll
Authors: Tredinnick-Rowe John
Published: July 2016

Thure von Uexküll's reputation as a pioneer in biosemiotics and also in psychosomatic medicine is well documented. It is easy to see these disciplines reflected in his notable publications, both in English and in German. However, if one spares the time to filter through all of his articles, monographs, conference papers and editorials in English and in German, a notable gap arises in his English language publications: that of clinical education. This gap in the English language literature may seem unimportant in and of itself, but it speaks volumes when we consider the total absence of medical semiotics in the curriculum of medical schools in the English speaking world. This runs in stark contrast to the strong traditions of psychosomatic medicine in Germany, which Thure von Uexküll largely helped to instil. Do the works of Thure von Uexküll offer a possible step towards a resurrection of medical semiotics in clinical education? This chapter attempts to explore the lesser known German literature on clinical education that Thure von Uexküll produced, and explore the role semiotics can play in Medical Education in the English speaking world. While also seeking to contrast this literature with other existing approaches in British and American medical schools who have attempted to reintroduce medical humanities and reflexive thinking into clinical education.
Oxidized subbituminous coal water additive has no adverse effect on growth performance or water consumption of growing broilers
Authors: Bench C.J. , Oryschak M.A. , Korver D.R.
Published: July 2016

Oxidized bituminous coal as a water supplement was studied to evaluate its effects on ammonia, litter, footpad lesions, and carcass attributes in broiler chickens. Bituminous coal water supplementation resulted in more severe footpad lesions; however, no significant effect was found for ammonia, litter, or carcass attributes under conditions in the present study.
Effects of conservation method on condensed tannin content, ruminal degradation, and in vitro intestinal digestion of purple prairie clover (Dalea purpureaVent.)
Authors: Huang Q.Q. , Jin L. , Xu Z. , Acharya S. , McAllister T.A. , Hu T.M. , Iwaasa A. , Schellenberg M. , Peng K. , Wang Y.
Published: July 2016

In situ and in vitro experiments were conducted to evaluate the effect of forage conservation method on the chemical composition, ruminal degradation, and intestinal digestion of purple prairie clover (PPC), which was conserved as freeze-dried forage (FD), silage (SIL), or hay (Hay). In situ dry matter (DM), neutral detergent fiber (NDF), and crude protein (CP) degradabilities were determined by incubating the forages in three rumen-cannulated heifers for 0, 1, 2, 4, 8, 24, 48, and 72 h. Intestinal DM and CP digestions were estimated by incubating 12 h ruminal in situ residues in a modified three-step in vitro procedure. Ensiling decreased (P < 0.001) extractable condensed tannins (CT) but increased (P < 0.001) protein- and fiber-bound CT compared with FD and Hay. The ruminal disappearance of CP at 8 and 24 h was affected by conservation method (P < 0.001), ranked as SIL > FD > Hay. The effective degradability of DM was lower (P < 0.001) for Hay than for FD and SIL. Ensiling lowered (P < 0.001) whereas haymaking increased (P < 0.001) intestinal digestion of CP compared with the fresh PPC. There were no differences in intestinal DM digestion among the three conserved forages. The results suggest that PPC conserved as Hay may conserve the biological activity of CT via preserving extractable CT more than as SIL, thus having the potential to improve protein utilization in ruminants.
Molecular characterization of pathogenic and nonpathogenic fowl aviadenovirus serotype 11 isolates
Authors: Slaine Patrick D. , Ackford James G. , Kropinski Andrew M. , Kozak Robert A. , Krell Peter J. , Nagy Éva
Published: July 2016

Fowl aviadenoviruses, many of which are of importance in veterinary medicine, are classified into 5 species. In this study, a pathogenic isolate and a nonpathogenic isolate of fowl aviadenovirus serotype 11 (FAdV-11) of species Fowl aviadenovirus D were characterized. Growth rates were analyzed for the 2 isolates, showing notable differences. The complete genomic sequences of the viruses were fully determined and were analyzed. The genomes of the 2 isolates showed 98.1% sequence identity and revealed 6 nonsynonymous mutations between the Ontario isolates. Two of the 6 mutations were also found in the sequences of recently published pathogenic Chinese fowl aviadenovirus 11 isolates, suggesting potential molecular markers that could be associated with pathogenesis. Deletions were found in the L5 region within the overlapping coding sequences for the 100, 22, and 33 kDa proteins, and these were found in only the nonpathogenic isolates. This molecular pattern was identified in FAdV-9, another nonpathogenic FAdV-D species virus. Furthermore, the tandem repeat regions varied dramatically; the pathogenic isolates contained a reduced number of tandem repeats compared with the nonpathogenic isolates. Lastly, a protein produced early in infection was analyzed using bioinformatics to determine its role in disease. This study highlights several candidate molecular determinants of avian adenovirus genomes related to pathogenicity.
Differential growth of body segments explains ontogenetic shifts in organ position for the Diamondback Water Snake (Nerodia rhombifer)
Authors: Anderson G.E. , Secor S.M.
Published: July 2016

As snakes grow, their organs move anteriorly relative to body size. We explored a developmental explanation for the ontogenetic shift in the relative position of internal organs for snakes using the Diamondback Water Snake (Nerodia rhombifer (Hallowell, 1852)). With age, this water snake’s heart, liver, small intestine, and right kidney move anteriorly by 2.5–5.0 percentage points of snout–vent length. The number of precaudal vertebrae did not vary due to size or sex. The anterior edge of the heart, liver, small intestine, and right kidney were typically aligned within a span of 4–8 vertebrae that likewise did not differ as a function of size or sex. Snakes exhibited a positive relationship between the number of precaudal vertebrae and the vertebra number aligned with each organ. Total length, centrum length, centrum width, ball width, height, and mass of eight vertebrae sampled at consistent vertebral number revealed that vertebrae in the middle region of the body grow at a greater rate than vertebrae at the anterior or distal ends of the body. For N. rhombifer, the observed forward shift in relative organ positions is the product of regional differences in the growth of body segments. Predictably, these differences arise from a developmental program generated by the differential expression of Hox genes.
On the existence of a Hofer type metric for Poisson manifolds
Authors: Rybicki Tomasz
Published: July 2016

An analogue of the Hofer metric [Formula: see text] on the Hamiltonian group [Formula: see text] of a Poisson manifold [Formula: see text] can be defined, but there is the problem of its nondegeneracy. First, we observe that [Formula: see text] is a genuine metric on [Formula: see text], when the union of all proper leaves of the corresponding symplectic foliation is dense. Next, we deal with the important class of integrable Poisson manifolds. Recall that a Poisson manifold is called integrable, if it can be realized as the space of units of a symplectic groupoid. Our main result states that [Formula: see text] is a Hofer type metric for every Poisson manifold, which admits a Hausdorff integration.
Electrochemical study of natural gas fueled electrodes for low temperature solid oxide fuel cell
Authors: Hussain M. Jafar , Raza Rizwan , Ahmad Mukhtar , Ali Akbar , Ahmad Imran , Syed Waqar A. A. , Janjua Naveed Kausar , Anis-ur-Rehman M. , Khan M. Ajmal , Shahid Shaukat A. , Abbas Ghazanfar
Published: July 2016

Fuel cell is undoubtedly widespread energy conversion technology, which can convert fuel (biogas) energy into electricity. Solid oxide fuel cell (SOFC) is one of the best choices among the fuel cell’s family due to high efficiency and fuel flexibility. In this study, zinc-based nanostructured [Formula: see text] electrode materials were successfully developed by solid state reaction. The proposed materials have been characterized by XRD and SEM. The electrical conductivities have been examined by four-probe DC method in the temperature range of 300–600[Formula: see text]C, the maximum values were recorded and found to be 12.019 and 5.106 S/cm at natural gas and air atmosphere, respectively. The electrochemical performance has been measured employing NK-SDC electrolyte material and their current density versus voltage and current density versus power density (I-V and I-P characteristics) have been drawn. The maximum power density was found to be 170 mW/cm2using natural gas as a bio-fuel over a temperature of 600[Formula: see text]C.
Superconductivity in a one-dimensional correlated quantum system
Authors: Ding Hanqin , Zhang Jun
Published: July 2016

We construct a one-dimensional (1D) theoretical model to clarify the occurrence of superconductivity. The weak-coupling (WC) theory allows a determination of the phase diagram. The constrained hopping induces additional two-body and three-body interactions. At half-filling, the three-body interaction is responsible for the triplet superconducting (TS) correlation. Away from half-filling, the two-body interaction works, favoring the singlet superconducting (SS) correlation. The results are expected to provide an insignificant insight into the superconductivity mechanism.
Constant-coupling approximation study of spin-1 Blume–Capel model
Authors: Ekiz Cesur
Published: July 2016

In this paper, the equilibrium properties of spin-1 Blume–Capel model are studied by using constant-coupling approximation. The formulation is based on developed by Obokata and Oguchi method, where the dependence upon the thermodynamic variables is determined by a set of two-couple nonlinear algebraic equations. The temperature dependence of the order parameters is examined to characterize the nature (continuous or discontinuous) of the phase transitions and to obtain the metastable and unstable branches. For the system, the effect of the uniaxial anisotropy parameter to phase transitions and stable, metastable and unstable states is discussed on the simple cubic lattice with the coordination number [Formula: see text] = 6.
First-principles study on the electronic and magnetic properties of the Zn0.75Mo0.25M(M = S,Se,Te)
Authors: Yin Zhu-Hua , Zhang Jian-Min , Xu Ke-Wei
Published: July 2016

The geometrical, electronic and magnetic properties of the Zn[Formula: see text]Mo[Formula: see text]M (M[Formula: see text]=[Formula: see text]S, Se and Te) have been studied by spin-polarized first-principles calculation. The optimized lattice constants of 5.535, 5.836 and 6.274 Å for M[Formula: see text]=[Formula: see text]S, Se and Te are related to the atomic radius of 1.09, 1.22 and 1.42 Å for S, Se and Te atoms, respectively. The Zn[Formula: see text]Mo[Formula: see text]M are magnetic half-metallic (HM) with the spin-down conventional band gaps of 2.899, 2.126 and 1.840 eV, while the HM band gaps of 0.393, 0.016 and 0.294 eV for M[Formula: see text]=[Formula: see text]S, Se and Te, respectively. At the Fermi level, the less than half-filled Mo-[Formula: see text] orbital hybridizated with the less M-[Formula: see text] orbital contributes only spin-up channel leading Zn[Formula: see text]Mo[Formula: see text]M an HM ferromagnetism. The tetrahedral crystal field formed by adjacent three Zn atoms and one M atom splits the spin-up channel (majority spin) of Mo-[Formula: see text] orbital into three-fold degenerate [Formula: see text] states at the Fermi level and double degenerate [Formula: see text] [Formula: see text] states below the Fermi level. The exchange splitting energies of the Zn[Formula: see text]Mo[Formula: see text]M are −2.611, −2.231 and −1.717 eV for M[Formula: see text]=[Formula: see text]S, Se and Te, respectively. The results provide an useful theoretical guidance for Zn[Formula: see text]Mo[Formula: see text]M applications in spintronic devices.
A dynamic evolution model for perfectly plastic plates
Authors: Maggiani Giovanni Battista , Mora Maria Giovanna
Published: July 2016

We consider the dynamic evolution of a linearly elastic-perfectly plastic thin plate subject to a purely vertical body load. As the thickness of the plate goes to zero, we prove that the three-dimensional evolutions converge to a solution of a certain reduced model. In the limiting model admissible displacements are of Kirchhoff–Love type. Moreover, the motion of the body is governed by an equilibrium equation for the stretching stress, a hyperbolic equation involving the vertical displacement and the bending stress, and a rate-independent plastic flow rule. Some further properties of the reduced model are also discussed.
Inotera Memories: Leader or Dreamer
Authors: Shyu Yih-Wen , Reinfeld William
Published: July 2016

This case can be divided into two sections. The first section focuses on how Inotera Memories can effectively analyze capital expenditure and return on investment for long-term capital budgeting in a capital-intensive, highly volatile and competitive industry. The following section is to highlight the strategy shift of Inotera. The DRAM business environment is highly volatile, and continuously requires large amounts of capital to improve process technologies, reduce production costs and achieve economies of scale. The challenge is greater because Inotera Memories is a joint venture of two entities with very different backgrounds, cultures and objectives, but which are not necessarily incompatible.

Fei Lin, an assistant vice president in Inotera, and Charles Kau, the president of Inotera, play the central roles in this case study. Fei has been instructed to prepare a report to the board of directors that presents an effective investment evaluation model to ensure the success of Inotera's business model and expansion project. On the other hand, Charles proposed the issue of strategy shift to determine how it has been implemented and whether it needs replacement by a new strategy to meet changed circumstances, new technology, and new market segments.
NOTE ON THE SMITH–WILSON INTEREST RATE CURVE
Authors: GACH FLORIAN
Published: July 2016

Since the entry into force of Solvency II as of 1 January 2016, all European insurance companies concerned have to use the Smith–Wilson interest rate curve to determine the value of their insurance obligations and thus of a substantial part of their balance sheet. Although Smith & Wilson introduce the underlying discount curve [Formula: see text] as the sum of a ‘long-term’ discount curve [Formula: see text] and a linear combination of the so-called Wilson function [Formula: see text] evaluated at different payment dates [Formula: see text], that is, [Formula: see text] a mathematically sound derivation of its shape is missing in the literature. The aim of this paper is to close this gap. To this end, we reformulate the infinite-dimensional optimization problem stated in Smith & Wilson (2000) within an analytically rigorous framework. We prove that it has a unique minimizer and explicitly derive the formula displayed above. In doing so, we show that [Formula: see text] is in fact the kernel function of a particular reproducing kernel Hilbert space, which is the key result to fully understanding the shape of [Formula: see text].
Line-transitive point-imprimitive linear spaces with number of points being a product of two primes
Authors: Guan Haiyan , Zhou Shenglin
Published: July 2016

The work studies the line-transitive point-imprimitive automorphism groups of finite linear spaces, and is underway on the situation when the numbers of points are products of two primes. Let [Formula: see text] be a non-trivial finite linear space with [Formula: see text] points, where [Formula: see text] and [Formula: see text] are two primes. We prove that if [Formula: see text] is line-transitive point-imprimitive, then [Formula: see text] is solvable.
NURTURING ENTREPRENEURIAL LEARNING THROUGH MENTORING
Authors: El HALLAM HORIA , ST-JEAN ÉTIENNE
Published: July 2016

This study highlights the factors that maximize the entrepreneur’s learning that occurs throughout a mentoring relationship. To achieve this, we conducted a hierarchical regression analysis involving a sample of 314 mentees participating in a business-mentoring program. The findings show that to maximize the learning from this relationship, the entrepreneur must perceive similarity and mutual trust with his or her mentor. The data shows that in exerting psychological and career-related functions, the mentor enables the entrepreneur’s learning.
Upstream controls on evolution of dryland alluvial megafans: Quaternary examples from the Kohrud Mountain Range, central Iran
Authors: Arzani Nasser , Jones Stuart J.
Published: July 2016

The relative importance of tectonics, climate, base level and source lithology as the primary controls on the evolution of alluvial fans is highly debated. This study examines the role of upstream catchment characteristics on the evolution of alluvial megafans by examining three Quaternary fans (the Kalahrud, Zefreh and Mughar fans) along the flanks of the Kohrud Mountain Range in central Iran. These fans formed in a tectonically active basin under arid to semi-arid climatic conditions. The key differences between the evolutionary trends of these fans are that their catchments are underlain by different bedrock types and they have different catchment shapes and outlet characteristics. The catchment of the Kalahrud fan is in a sedimentary terrain with limited sediment supply, whereas the bedrock lithologies of the Zefreh and Mughar fans are fractured and weathered igneous rocks. However, the evolution of the Mughar fan is also controlled by the tilting of the catchment towards a wide apex and lateral shifting in the catchment outlet/fan feeder channel position. These variables resulted in relatively large-scale incision in the Kalahrud and Mughar fans that is absent in the aggradational trend of the Zefreh fan. Upstream lithological and structural controls are the dominant drivers behind the development and evolution of alluvial megafans.
Defining human insulin-like growth factor I gene regulation
Authors: Mukherjee Aditi , Alzhanov Damir , Rotwein Peter
Published: July 2016

Growth hormone (GH) plays an essential role in controlling somatic growth and in regulating multiple physiological processes in humans and other species. Insulin-like growth factor I (IGF-I), a conserved, secreted 70-amino acid peptide, is a critical mediator of many of the biological effects of GH. Previous studies have demonstrated that GH rapidly and potently promotes IGF-I gene expression in rodents and in some other mammals through the transcription factor STAT5b, leading to accumulation of IGF-I mRNAs and production of IGF-I. Despite this progress, very little is known about how GH or other trophic factors control human IGF1 gene expression, in large part because of the absence of any cellular model systems that robustly express IGF-I. Here, we have addressed mechanisms of regulation of human IGF-I by GH after generating cells in which the IGF1 chromosomal locus has been incorporated into a mouse cell line. Using this model, we found that physiological levels of GH rapidly stimulate human IGF1 gene transcription and identify several potential transcriptional enhancers in chromatin that bind STAT5b in a GH-regulated way. Each of the putative enhancers also activates a human IGF1 gene promoter in reconstitution experiments in the presence of the GH receptor, STAT5b, and GH. Thus we have developed a novel experimental platform that now may be used to determine how human IGF1 gene expression is controlled under different physiological and pathological conditions.
Left ventricular twist mechanics in the context of normal physiology and cardiovascular disease: a review of studies using speckle tracking echocardiography
Authors: Stöhr Eric J. , Shave Rob E. , Baggish Aaron L. , Weiner Rory B.
Published: July 2016

The anatomy of the adult human left ventricle (LV) is the result of its complex interaction with its environment. From the fetal to the neonatal to the adult form, the human LV undergoes an anatomical transformation that finally results in the most complex of the four cardiac chambers. In its adult form, the human LV consists of two muscular helixes that surround the midventricular circumferential layer of muscle fibers. Contraction of these endocardial and epicardial helixes results in a twisting motion that is thought to minimize the transmural stress of the LV muscle. In the healthy myocardium, the LV twist response to stimuli that alter preload, afterload, or contractility has been described and is deemed relatively consistent and predictable. Conversely, the LV twist response in patient populations appears to be a little more variable and less predictable, yet it has revealed important insight into the effect of cardiovascular disease on LV mechanical function. This review discusses important methodological aspects of assessing LV twist and evaluates the LV twist responses to the main physiological and pathophysiological states. It is concluded that correct assessment of LV twist mechanics holds significant potential to advance our understanding of LV function in human health and cardiovascular disease.
Increase of cortical cerebral blood flow and further cerebral microcirculatory effects of Serelaxin in a sheep model
Authors: Bischoff Sabine J. , Schmidt Martin , Lehmann Thomas , Irintchev Andrey , Schubert Harald , Jung Christian , Schwab Matthias , Huber Otmar , Matziolis Georg , Schiffner René
Published: July 2016

Serelaxin, recombinant human relaxin-2, modulates endothelial vasodilatory functionality and is under evaluation for treatment of acute heart failure. Little is known about acute effects on cerebral perfusion. We tested the hypothesis that Serelaxin might also have effects on the cerebral microcirculation in a sheep model, which resembles human brain structure quite well. We used laser Doppler flowmetry and sidestream dark-field (SDF) imaging techniques, which are reliable tools to continuously assess dynamic changes in cerebral perfusion. Laser Doppler flowmetry shows that bolus injection of 30 μg Serelaxin/kg body wt induces an increase ( P = 0.006) to roughly 150% of cortical cerebral blood flow (CBF), whereas subcortical CBF remains unchanged ( P = 0.688). The effects on area-dependent CBF were significantly different after the bolus injection ( P = 0.042). Effects on cortical CBF were further confirmed by SDF imaging. The bolus injection of Serelaxin increased total vessel density to 127% ( P = 0.00046), perfused vessel density to 145% ( P = 0.024), and perfused capillary density to 153% ( P = 0.024). Western blotting confirmed the expression of relaxin receptors RXFP1 and truncated RXFP2-variants in the respective brain regions, suggesting a possible contribution of RXFP1 on the effects of Serelaxin. In conclusion, the injection of a high dose of Serelaxin exerts quick effects on the cerebral microcirculation. Therefore, Serelaxin might be suitable to improve cortical microcirculation and exert neuroprotective effects in clinically relevant scenarios that involve cortical hypoperfusion. These findings need to be confirmed in relevant experimental settings involving cerebral cortical hypoperfusion and can possibly be translated into clinical practice.
Myocardial energetics is not compromised during compensated hypertrophy in the Dahl salt-sensitive rat model of hypertension
Authors: Tran Kenneth , Han June-Chiew , Taberner Andrew J. , Barrett Carolyn J. , Crampin Edmund J. , Loiselle Denis S.
Published: July 2016

Salt-induced hypertension leads to development of left ventricular hypertrophy in the Dahl salt-sensitive (Dahl/SS) rat. Before progression to left ventricular failure, the heart initially undergoes a compensated hypertrophic response. We hypothesized that changes in myocardial energetics may be an early indicator of transition to failure. Dahl/SS rats and their salt-resistant consomic controls (SS-13BN) were placed on either a low- or high-salt diet to generate four cohorts: Dahl-SS rats on a low- (Dahl-LS) or high-salt diet (Dahl-HS), and SS-13BN rats on a low- (SSBN-LS) or high-salt diet (SSBN-HS). We isolated left ventricular trabeculae and characterized their mechanoenergetic performance. Our results show, at most, modest effects of salt-induced compensated hypertrophy on myocardial energetics. We found that the Dahl-HS cohort had a higher work-loop heat of activation (estimated from the intercept of the heat vs. relative afterload relationship generated from work-loop contractions) relative to the SSBN-HS cohort and a higher economy of contraction (inverse of the slope of the heat vs. active stress relation) relative to the Dahl-LS cohort. The maximum extent of shortening and maximum shortening velocity of the Dahl/SS groups were higher than those of the SS-13BN groups. Despite these differences, no significant effect of salt-induced hypertension was observed for either peak work output or peak mechanical efficiency during compensated hypertrophy.
Structure and hemodynamics of vascular networks in the chorioallantoic membrane of the chicken
Authors: Maibier Martin , Reglin Bettina , Nitzsche Bianca , Xiang Weiwei , Rong Wen Wei , Hoffmann Björn , Djonov Valentin , Secomb Timothy W. , Pries Axel R.
Published: July 2016

The chick chorioallantoic membrane (CAM) is extensively used as an in vivo model. Here, structure and hemodynamics of CAM vessel trees were analyzed and compared with predictions of Murray's law. CAM microvascular networks of Hamburger-Hamilton stage 40 chick embryos were scanned by videomicroscopy. Three networks with ∼3,800, 580, and 480 segments were digitally reconstructed, neglecting the capillary mesh. Vessel diameters ( D) and segment lengths were measured, and generation numbers and junctional exponents at bifurcations were derived. In selected vessels, flow velocities ( v) and hematocrit were measured. Hemodynamic simulations, incorporating the branching of capillaries from preterminal vessels, were used to estimate v, volume flow, shear stress (τ), and pressure for all segments of the largest network. For individual arteriovenous flow pathways, terminal arterial and venous generation numbers are negatively correlated, leading to low variability of total topological and morphological pathway lengths. Arteriolar velocity is proportional to diameter ( v∝ D1.03measured, v∝ D0.93modeling), giving nearly uniform τ levels (τ∝ D0.05). Venular trees exhibit slightly higher exponents ( v∝ D1.3, τ∝ D0.38). Junctional exponents at divergent and convergent bifurcations were 2.05 ± 1.13 and 1.97 ± 0.95 (mean ± SD) in contrast to the value 3 predicted by Murray's law. In accordance with Murray's law, τ levels are (nearly) maintained in CAM arterial (venular) trees, suggesting vascular adaptation to shear stress. Arterial and venous trees show an interdigitating arrangement providing homogeneous flow pathway properties and have preterminal capillary branches. These properties may facilitate efficient oxygen exchange in the CAM during rapid embryonic growth.
Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770
Authors: Gentzsch Martina , Ren Hong Y. , Houck Scott A. , Quinney Nancy L. , Cholon Deborah M. , Sopha Pattarawut , Chaudhry Imron G. , Das Jhuma , Dokholyan Nikolay V. , Randell Scott H. , Cyr Douglas M.
Published: July 2016

Cystic fibrosis (CF) is a lethal recessive genetic disease caused primarily by the F508del mutation in the CF transmembrane conductance regulator (CFTR). The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D. Orkambi is a drug containing VX-770 and corrector VX809 and is approved for treatment of CF patients homozygous for F508del, which has folding and gating defects. At least 30% of CF patients are heterozygous for the F508del mutation with the other allele encoding for one of many different rare CFTR mutations. Treatment of heterozygous F508del patients with VX-809 and VX-770 has had limited success, so it is important to identify heterozygous patients that respond to CFTR modulator therapy. R117H is a more prevalent rare mutation found in over 2,000 CF patients. In this study we investigated the effectiveness of VX-809/VX-770 therapy on restoring CFTR function in human bronchial epithelial (HBE) cells from R117H/F508del CF patients. We found that VX-809 stimulated more CFTR activity in R117H/F508del HBEs than in F508del/F508del HBEs. R117H expressed exclusively in immortalized HBEs exhibited a folding defect, was retained in the ER, and degraded prematurely. VX-809 corrected the R117H folding defect and restored channel function. Because R117 is involved in ion conductance, VX-770 acted additively with VX-809 to restore CFTR function in chronically treated R117H/F508del cells. Although treatment of R117H patients with VX-770 has been approved, our studies indicate that Orkambi may be more beneficial for rescue of CFTR function in these patients.
Intermittent hypoxia promotes recovery of respiratory motor function in spinal cord-injured mice depleted of serotonin in the central nervous system
Authors: Komnenov Dragana , Solarewicz Julia Z. , Afzal Fareeza , Nantwi Kwaku D. , Kuhn Donald M. , Mateika Jason H.
Published: July 2016

We examined the effect of repeated daily exposure to intermittent hypoxia (IH) on the recovery of respiratory and limb motor function in mice genetically depleted of central nervous system serotonin. Electroencephalography, diaphragm activity, ventilation, core body temperature, and limb mobility were measured in spontaneously breathing wild-type (Tph2+/+) and tryptophan hydroxylase 2 knockout (Tph2−/−) mice. Following a C2hemisection, the mice were exposed daily to IH (i.e., twelve 4-min episodes of 10% oxygen interspersed with 4-min normoxic periods followed by a 90-min end-recovery period) or normoxia (i.e., sham protocol, 21% oxygen) for 10 consecutive days. Diaphragm activity recovered to prehemisection levels in the Tph2+/+and Tph2−/−mice following exposure to IH but not normoxia [Tph2+/+1.3 ± 0.2 (SE) vs. 0.3 ± 0.2; Tph2−/−1.06 ± 0.1 vs. 0.3 ± 0.1, standardized to prehemisection values, P < 0.01]. Likewise, recovery of tidal volume and breathing frequency was evident, although breathing frequency values did not return to prehemisection levels within the time frame of the protocol. Partial recovery of limb motor function was also evident 2 wk after spinal cord hemisection. However, recovery was not dependent on IH or the presence of serotonin in the central nervous system. We conclude that IH promotes recovery of respiratory function but not basic motor tasks. Moreover, we conclude that spontaneous or treatment-induced recovery of respiratory and motor limb function is not dependent on serotonin in the central nervous system in a mouse model of spinal cord injury.
Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue
Authors: Knight Jason M. , Kim Eunji , Ivanov Ivan , Davidson Laurie A. , Goldsby Jennifer S. , Hullar Meredith A. J. , Randolph Timothy W. , Kaz Andrew M. , Levy Lisa , Lampe Johanna W. , Chapkin Robert S.
Published: July 2016

The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs. epithelial cells in the sigmoid colon and rectum. Using RNA-seq, we demonstrate that tissue type and location patterns of gene expression and upstream regulatory pathways are distinct. For example, consistent with a key role of stroma in the crypt niche, mRNAs associated with immunoregulatory and inflammatory processes (i.e., CXCL14, ANTXR1), smooth muscle contraction (CALD1), proliferation and apoptosis (GLP2R, IGFBP3), and modulation of extracellular matrix (MMP2, COL3A1, MFAP4) were all highly expressed in the stroma. In comparison, HOX genes (HOXA3, HOXD9, HOXD10, HOXD11, and HOXD-AS2, a HOXD cluster antisense RNA 2), and WNT5B expression were also significantly higher in sigmoid colon compared with the rectum. These findings provide strong impetus for considering colorectal tissue subtypes and location in future observational studies and clinical trials designed to evaluate the effects of exposures on colonic health.
Transcriptome meta-analysis of three follicular compartments and its correlation with ovarian follicle maturity and oocyte developmental competence in cows
Authors: Khan Daulat Raheem , Landry David A. , Fournier Éric , Vigneault Christian , Blondin Patrick , Sirard Marc-André
Published: July 2016

Oocyte developmental competence in superstimulated cows is dependent in part on the duration of the FSH coasting. FSH coasting refers to superstimulation with FSH (2 days of endogenous FSH following follicle ablation and 3 days of FSH injections) followed by no FSH for a specific duration. The optimal duration varies among individuals. FSH coasting appears to modulate the transcriptome of different follicular compartments, which cooperate as a single functional unit. However, the integrative effects of FSH coasting on different follicular compartments remain ambiguous. Meta-analysis of three independent transcriptome studies, each focused on a single cell type (granulosa, cumulus, and oocyte) during FSH coasting, allowed the identification of 12 gene clusters with similar time-course expression patterns in all three compartments. Network analysis identified HNF4A (involved in metabolic functions) and ELAVL1 (an RNA-binding protein) as hub genes regulated respectively upward and downward in the clusters enriched at the optimal coasting time, and APP (involved in mitochondrial functions) and COPS5 (a member of the COP9 signalosome) as hub genes regulated respectively upwards and downwards in the clusters enriched progressively throughout the coasting period. We confirmed the effects on HNF4A downstream targets ( TTR, PPL) and other hub genes ( ELAVL1, APP, MYC, and PGR) in 30 cows with RT-quantitative PCR. The correlation of hub gene expression levels with FSH coasting indicated that a combination of these genes could predict oocyte competence with 83% sensitivity, suggesting that they are potential biomarkers of follicle differentiation. These findings could be used to optimize FSH coasting on an individual basis.