bluuebunny/crossref_metadata_2025 huggingface dataset:
An Automated Microwell Platform for Large-Scale Single Cell RNA-Seq
Authors: Yuan Jinzhou , Sims Peter A.
Published: August 2016

Recent developments have enabled rapid, inexpensive RNA sequencing of thousands of individual cells from a single specimen, raising the possibility of unbiased and comprehensive expression profiling from complex tissues. Microwell arrays are a particularly attractive microfluidic platform for single cell analysis due to their scalability, cell capture efficiency, and compatibility with imaging. We report an automated microwell array platform for single cell RNA-Seq with significantly improved performance over previous implementations. We demonstrate cell capture efficiencies of >50%, compatibility with commercially available barcoded mRNA capture beads, and parallel expression profiling from thousands of individual cells. We evaluate the level of cross-contamination in our platform by both tracking fluorescent cell lysate in sealed microwells and with a human-mouse mixed species RNA-Seq experiment. Finally, we apply our system to comprehensively assess heterogeneity in gene expression of patient-derived glioma neurospheres and uncover subpopulations similar to those observed in human glioma tissue.
Mathematical Methods for Modeling Chemical Reaction Networks
Authors: Carden Justin , Pantea Casian , Craciun Gheorge , Machiraju Raghu , Mallick Parag
Published: August 2016

Cancer’s cellular behavior is driven by alterations in the processes that cells use to sense and respond to diverse stimuli. Underlying these processes are a series of chemical processes (enzyme-substrate, protein-protein, etc.). Here we introduce a set of mathematical techniques for describing and characterizing these processes.
Female mice lacking Xist RNA show partial dosage compensation and survive to term
Authors: Yang Lin , Kirby James E. , Sunwoo Hongjae , Lee Jeannie T.
Published: August 2016

X-chromosome inactivation (XCI) compensates for differences in X-chromosome number between male and female mammals. XCI is orchestrated by Xist RNA, whose expression in early development leads to transcriptional silencing of one X chromosome in the female. Knockout studies have established a requirement for Xist with inviability of female embryos that inherit an Xist deletion from the father. Here, we report that female mice lacking Xist RNA can, surprisingly, develop and survive to term. Xist-null females are born at lower frequency and are smaller at birth, but organogenesis is mostly normal. Transcriptomic analysis indicates significant overexpression of hundreds of X-linked genes across multiple tissues. Therefore, Xist-null mice can develop to term in spite of a deficiency of dosage compensation. However, the degree of X-autosomal dosage imbalance was less than anticipated (1.14-fold to 1.36-fold). Thus, partial dosage compensation can be achieved without Xist, supporting the idea of inherent genome balance. Nevertheless, to date, none of the mutant mice has survived beyond weaning stage. Sudden death is associated with failure of postnatal organ maturation. Our data suggest Xist-independent mechanisms of dosage compensation and demonstrate that small deviations from X-autosomal balance can have profound effects on overall fitness.
Assessment of the Proposed India-China Free Trade Agreement: A General Equilibrium Approach
Authors: Arora Rahul , Singh Sarbjit , Mathur Somesh K.
Published: August 2016

Purpose

The present study is an attempt to evaluate the impact of the proposed India-China free trade agreement (FTA) in goods trade on both countries under a static general equilibrium framework.

Design/Methodology/Approach

The study has utilized the Global Trade Analysis Project (GTAP) model of world trade with the presence of skilled and unskilled unemployment in the world. For analysis purposes, 57 GTAP sectors, representing the whole regional economy, have been aggregated into 43 sectors and 140 GTAP regions, representing the whole world, have been aggregated into 19 regions. The study has also used the updated tariff rates provided by the World Trade Organization for better results.

Findings

The preliminary analysis using trade indicators depicted that by utilizing their own comparative advantage, both of the countries can maximize their gains by exporting more to the world. The simulation results from the GTAP analysis revealed that a tariff reduction in all goods trade would be more beneficial for both the countries than the tariff reduction in each other's specialized products. All other regions lose in terms of shifting the Indian imports towards China in a post-simulation environment. Regions with a significant loss are: the European Union (28 members), Southeast Asia, the Unites States, Japan, Korea, West Asia, and the European Free Trade Association (EFTA).

Originality/Value

The disaggregated sector-wise analysis has been performed using the latest available GTAP database, version 9.
Teaching and learning
Authors: Samkin Grant , Stainbank Lesley
Published: August 2016

Purpose

Positioned within a framework of challenges facing universities, this paper aims to focus on challenges faced by teachers of accounting as a business discipline to ensure it remains relevant in a fast-moving and changing environment.

Design/methodology/approach

Drawing on a variety of sources, this paper explores a number of issues surrounding teaching and learning in the current university environment. The seven papers that make up the special issue are located within a framework which is used to illustrate how each one contributes to the field. This paper is primarily discursive in nature.

Findings

The theoretical, methodological and empirical approaches used in the papers that make up this special issue are described. In addition, the paper suggests that to remain relevant, teaching and learning will remain an important area for future research.

Practical implications

This paper on teaching and learning is of interest to accounting teachers and researchers, university managers and members of the accounting profession.

Originality/value

This special issue provides a range of examples of research relevant to teaching and learning and sets an agenda for future research.
The playground of the rich? Growing social business in the 21st century
Authors: Steiner Artur , Teasdale Simon
Published: August 2016

Purpose

This paper aims to explore how nascent social businesses move beyond the incubation phase and it develops understanding of how early-stage social businesses access finance to achieve growth.

Design/methodology/approach

This exploratory and inductive study is based on four focus group discussions with early-stage social entrepreneurs, “successful” social entrepreneurs who had achieved growth, and social impact investors.

Findings

Social capital allows a social business founder to access financial capital to “prove their concept”, or to directly attract investment from family and friends for start-up costs. To gain funding, social entrepreneurs present the desired image of the heroic change-maker. Interestingly, creating the right impression is equally important in securing financial capital as the “hard-work” itself.

Research limitations/implications

This study was conducted in London, which, like many other “global” cities, has a unique business environment. The study is exploratory in nature. Further work in this area is required to draw more definitive conclusions.

Practical implications

Financial products offered to social businesses are often dispersed and inappropriate. The study indicates that access to “soft loans” and grants is critical in the early stages of social business growth and that social entrepreneurs use both formal and informal funding sources to develop their businesses. Where a person is not connected to wealthy acquaintances either through family, or through social networks, they may often struggle to access finance in a world where the network’s resources appear to be as important as the entrepreneur’s resourcefulness. This has particular implications for the demographic make-up of “successful social entrepreneurs” operating social businesses, as these may be drawn from the most privileged and/or well-connected members of a group which already appears skewed towards white middle-class males.

Social implications

This study highlights that current support structures favour relatively privileged social entrepreneurs rather than encompassing and empowering those disadvantaged, social minority groups and those in the greatest need. This is important because social business is often portrayed, possibly incorrectly, as a mechanism for addressing poverty through empowerment of disadvantaged groups.

Originality/value

Research in social business development has largely neglected the social and cultural dynamics that embed start-ups. This paper tackles this gap and contributes to building knowledge in the area of early-stage social business development.
Lord John Browne: beyond CSR – why business needs to engage more radically with society
Authors: Leavy Brian
Published: August 2016

Purpose

This interview with petroleum executive John Browne, lead author of Connect: How Companies Succeed by Engaging Radically with Society, discusses sustainability practices that could be more successful than those of the Corporate Social Responsibility (CSR) movement.

Design/methodology/approach

Lord Browne, a British peer, was CEO of BP (British Petroleum) from 1995 to 2007 and is currently executive chairman of L1 Energy, He was interviewed by Prof. Brian Leavy, an S&L contributing editor

Findings

Connected leadership means integrating societal and environmental considerations into core business strategy at every level of the company.

Practical implications

The key lesson for business leaders in the wake of …accidents and scandals is that reputation is an outcome of your core business activity, not something constructed alongside it.

Social implications

Shareholder value, as a theory, presents a false tension between serving stakeholders and shareholders.

Originality/value

Browne was the first Big Oil chief executive to acknowledge the link between man-made carbon emissions and global warming. His insights into integrating social responsibility and corporate strategy are cutting edge.
Learning to be a leader
Authors: Allio Robert J.
Published: August 2016

Purpose

The author believes it is possible to select a better strategy for improving leadership effectiveness. His hypothesis: although leadership cannot be taught, paradoxically, leadership can be learned.

Design/methodology/approach

The playbook for developing potential leaders comprises these three elements: Establish a leadership identity and persona. Acquire relevant leadership knowledge and skills. Practice acts of leadership.

Findings

We preach the need for moral leaders, but in pursuit of maximizing shareholder returns and stock option bonuses for CEOs society embraces rogues and celebrates robber barons who successfully elbow their way ahead of the pack!

Practical implications

Whatever other personal traits the leader may possess, the one absolute prerequisite is the judicious exercise of power – specifically, the power to change the way followers think and behave.

Originality/value

Success leadership ultimately depends on the ability to communicate, to tell a story that explains the proposed corporate vector and inspires the followers to sign on for the adventure.
How to make the whole organization “Agile”
Authors: Denning Stephen
Published: August 2016

Purpose

Agile is the umbrella term for a family of management practices, which include Scrum, Kanban, and Lean. To investigate Agile management as it was being practiced in large firms, in 2015 Scrum Alliance, whose mission is “to transform the world of work,” launched a Learning Consortium for the Creative Economy (LC), composed of a group of firms that included Microsoft, Ericsson, Magna International, Riot Games and others.

Design/methodology/approach

The group conducted site visits to learn from each other’s experiences with Agile. The questions to be explored included: To what extent are Agile management practices in fact occurring at scale in old and new firms? How effective are these management practices? Is it possible for the whole firm, particularly older firms with entrenched bureaucratic cultures, to become Agile?

Findings

The LC found that Agile management is already taking hold in large-scale implementations in both new and old firms. The LC observed that some firms were implementing Agile for large-scale, complex business challenges in areas beyond software, including operations where reliability is an issue.

Practical implications

Agile was seen as a different way of understanding and acting in the world. The successful firms were “being Agile,” not merely “doing Agile” within their existing management framework.

Originality/value

In the world of Agile management, delivering value to customers is the goal of every individual in the organization. Profits are seen as the result, not the goal. The Learning consortium sites visit offer managers an opportunity to study this philosophy in practice.
Strategic Planning and Management in Local Government in Norway: Status after Three Decades
Authors: Johnsen Åge
Published: August 2016

Strategic planning and management was introduced in the public sector more than three decades ago and has become a core component in many new public management reforms. Although strategy has been widely adopted in the public sector, the knowledge base regarding its practices and its impacts remains scarce, particularly outside Anglo‐American countries. This article replicates an American and British survey by analysing the adoption and impacts of strategic planning and management in Norwegian municipalities. The results show that, in 2012, a majority of the Norwegian municipalities used strategic planning and management, and that the respondents viewed the impact positively overall. Municipalities that had chosen the strategic stance of prospector and had financial resources from positive net operating results margin adopted strategic planning and management more than other municipalities. Municipalities with a high degree of strategic management and high stakeholder involvement had better perceived impacts of strategic planning than other municipalities.
Global Investment Environment of the Post‐Quantitative Easing World: The ‘new‐old’ and ‘new‐new’ Normal
Authors: Melvin Michael
Published: August 2016

Abstract

Global markets since late 2007 are not ‘normal’, where normal means market conditions we would expect to observe going forward in the absence of any new economic shocks. Financial markets have been dominated by extraordinary central bank policies that were created to deal with challenging market conditions reflecting heightened risk aversion and illiquidity. Markets in the future will have some characteristics that look more like the market conditions observed in the pre‐crisis period, which I call the ‘new‐old normal’ and other conditions that differ from the past, which I call the ‘new‐new normal’. I first review what happened during the financial crisis in terms of developments in three asset classes, equities, fixed income and currencies, to place the forward‐looking view in proper context. Then the transition period from the quantitative easing (QE) era of exceptional monetary policy to post‐QE markets is discussed. Post‐transition, we will see some features of the post‐QE world that will resemble pre‐crisis market conditions, the ‘new‐old normal’ with higher policy interest rates, wider cross‐country interest differentials, lower cross‐asset return correlations and a resurgence of the importance of cross‐country differences in fundamentals in international investing. However, some features of the post‐QE investment environment will be unlike anything observed in the past: the ‘new‐new normal’ with reduced liquidity and more days of exceptionally large volatility and asset price moves due to regulatory effects resulting in a reduced ability of market‐makers to provide inventory buffers for counterparties and electronic trading venues that shut down trading in high volatility periods; low inflation; flatter yield curves; and emerging markets providing less opportunity for diversification gains as they converge to developed financial market characteristics.
Red cell alloimmunisation in patients with different types of infections
Authors: Evers Dorothea , van der Bom Johanna G. , Tijmensen Janneke , Middelburg Rutger A. , de Haas Masja , Zalpuri Saurabh , de Vooght Karen M. K. , van de Kerkhof Daan , Visser Otto , Péquériaux Nathalie C. V. , Hudig Francisca , Zwaginga Jaap Jan
Published: August 2016

Red cell alloantigen exposure can cause alloantibody‐associated morbidity. Murine models have suggested that inflammation modulates red cell alloimmunisation. This study quantifies alloimmunisation risks during infectious episodes in humans. We performed a multicentre case–control study within a source population of patients receiving their first and subsequent red cell transfusions during an 8‐year follow‐up period. Patients developing a first transfusion‐induced red cell alloantibody (N = 505) were each compared with two similarly exposed, but non‐alloimmunised controls (N = 1010) during a 5‐week ‘alloimmunisation risk period’ using multivariate logistic regression analysis. Transfusions during ‘severe’ bacterial (tissue‐invasive) infections were associated with increased risks of alloantibody development [adjusted relative risk (RR) 1·34, 95% confidence interval (95% CI) 0·97–1·85], especially when these infections were accompanied with long‐standing fever (RR 3·06, 95% CI 1·57–5·96). Disseminated viral disorders demonstrated a trend towards increased risks (RR 2·41, 95% CI 0·89–6·53), in apparent contrast to a possible protection associated with Gram‐negative bacteraemia (RR 0·58, 95% CI 0·13–1·14). ‘Simple’ bacterial infections, Gram‐positive bacteraemia, fungal infections, maximum C‐reactive protein values and leucocytosis were not associated with red cell alloimmunisation. These findings are consistent with murine models. Confirmatory research is needed before patients likely to develop alloantibodies may be identified based on their infectious conditions at time of transfusion.
Integration of 60,000 exomes and ACMG guidelines question the role of Catecholaminergic Polymorphic Ventricular Tachycardia‐associated variants
Authors: Paludan‐Müller C. , Ahlberg G. , Ghouse J. , Herfelt C. , Svendsen J.H. , Haunsø S. , Kanters J.K. , Olesen M.S.
Published: August 2016

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a highly lethal cardiac arrhythmia disease occurring during exercise or psychological stress. CPVT has an estimated prevalence of 1:10,000 and has mainly been associated with variants in calcium‐regulating genes. Identification of potential false‐positive pathogenic variants was conducted by searching the Exome Aggregation Consortium (ExAC) database (n = 60,706) for variants reported to be associated with CPVT. The pathogenicity of the interrogated variants was assessed using guidelines from the American College of Medical Genetics and Genomics (ACMG) and in silico prediction tools. Of 246 variants 38 (15%) variants previously associated with CPVT were identified in the ExAC database. We predicted the CPVT prevalence to be 1:132. The ACMG standards classified 29% of ExAC variants as pathogenic or likely pathogenic. The in silico predictions showed a reduced probability of disease‐causing effect for the variants identified in the exome database (p < 0.001). We have observed a large overrepresentation of previously CPVT‐associated variants in a large exome database. Based on the frequency of CPVT in the general population, it is less likely that the previously proposed variants are associated with a highly penetrant monogenic form of the disease.
Matrix Metalloproteinase‐1 Expression in Women With and Without Pelvic Organ Prolapse: A Systematic Review and Meta‐analysis
Authors: Feng Y , Wang Y , Yan B , Li L , Deng Y
Published: August 2016

This meta‐analysis was conducted to estimate the association between matrix metalloproteinase‐1 (MMP‐1) expression and pelvic organ prolapse (POP) in women. Relevant studies published before 6 December 2015 were identified by searching PubMed, Ovid, EBSCO, and EMBASE. A total number of five case–control studies, including 182 POP cases and 192 controls, were identified. The results indicated that women without POP had a lower MMP‐1 level of expression compared with women with POP (odds ratio = 0.54, 95% confidence interval: 0.43–0.67, P = 0.000). After stratification by biopsy site, ethnicity, or menopausal status, this finding was also confirmed in the subgroup analysis with no significant changes. Egger's linear regression test revealed a potential publication bias (P = 0.028). The findings of our study indicate that women who suffer from POP have a higher expression level of MMP‐1 than women without POP.
Examining the effects of climate change and species invasions on Ontario walleye populations: can walleye beat the heat?
Authors: Van Zuiden Thomas M. , Sharma Sapna
Published: August 2016

Aim

The combined effects of multiple environmental stressors continue to threaten global biodiversity, yet predicting how biotic interactions between native and invasive species may change across a landscape in a multiple stressor environment is relatively understudied. We aim to identify how the invasion of smallmouth bass (Micropterus dolomeiu) may influence native walleye (Sander vitreus) populations across Ontario lakes at the landscape scale in a changing climate.

Location

Ontario, Canada.

Methods

Using a database that included the abundance and occurrence of over 130 fish species, lake chemistry and lake morphology for 722 lakes, a redundancy analysis was conducted to identify environmental conditions preferred by walleye and smallmouth bass. Multiple linear regression models were then developed to identify the relationship between walleye and multiple stressors (including climate change and biotic interactions with invasive species). Using future scenarios of climate change, we were then able to project future walleye–smallmouth bass co‐occurrences.

Results

Smallmouth bass were found to prefer different environmental conditions than walleye; however, when walleye and smallmouth bass were found in the same lakes, walleye abundance was reduced almost threefold. Multiple regression models further suggested that there are fewer walleye in lakes with smallmouth bass. Subsequently, we predicted that under future scenarios of climate change the overlapping co‐occurrence of walleye and smallmouth bass may increase by 86–332% by the year 2070.

Main conclusions

We illustrate the importance of including multiple environmental stressors in statistical models when attempting to understand how native species will be impacted by invasive species and climate change. While independently climate change is anticipated to lower walleye abundances across Ontario, this change is expected to be exacerbated by invasions of warmwater predators.
Giant left atrial appendage aneurysm compressing the left anterior descending coronary artery
Authors: Wagdy Kerolos , Samaan Amir , Romeih Soha , Simry Walid , Afifi Ahmed , Hassan Mohamed
Published: August 2016

Left atrial appendage aneurysm (LAAA) is a rare congenital structural heart disease. It is often diagnosed by echocardiography; however, other imaging modalities can add to its diagnosis and its potential effects on the surrounding structures. A 16‐year‐old boy presented with dyspnea and palpitation. Transthoracic echocardiography showed a large LAAA communicating with the LA through a narrow neck with impaired left ventricular (LV) systolic function. Multidetector cardiac tomography showed that the LAAA is compressing the left anterior descending artery. The LAAA was surgically resected followed by improvement of the LV systolic function.
Local bumble bee decline linked to recovery of honey bees, drought effects on floral resources
Authors: Thomson Diane M.
Published: August 2016

Time series of abundances are critical for understanding how abiotic factors and species interactions affect population dynamics, but are rarely linked with experiments and also scarce for bee pollinators. This gap is important given concerns about declines in some bee species. I monitored honey bee (Apis mellifera) and bumble bee (Bombus spp.) foragers in coastal California from 1999, when feral A. mellifera populations were low due to Varroa destructor, until 2014. Apis mellifera increased substantially, except between 2006 and 2011, coinciding with declines in managed populations. Increases in A. mellifera strongly correlated with declines in Bombus and reduced diet overlap between them, suggesting resource competition consistent with past experimental results. Lower Bombus numbers also correlated with diminished floral resources. Declines in floral abundances were associated with drought and reduced spring rainfall. These results illustrate how competition with an introduced species may interact with climate to drive local decline of native pollinators.
The TRAIL to acne pathogenesis: let's focus on death pathways
Authors: Melnik Bodo C.
Published: August 2016

This hypothesis presents acne as a PI3K‐Akt‐mTORC1‐driven pro‐survival disease of the sebaceous follicle with impaired TRAIL‐mediated death signalling. It is predicted that anti‐acne agents such as isotretinoin enhance death signalling and thereby readjust the disturbed balance of pro‐survival and death signalling of the sebaceous follicle in acne vulgaris. For this purpose, immortalized sebocyte cultures are regarded as inapproproate models to study the key features of acne pathogenesis.
Can intensification reduce emission intensity of biofuel through optimized fertilizer use? Theory and the case of oil palm in Indonesia
Authors: van Noordwijk Meine , Khasanah Ni'matul , Dewi Sonya
Published: August 2016

Closing yield gaps through higher fertilizer use increases direct greenhouse gas emissions but shares the burden over a larger production volume. Net greenhouse gas (GHG) footprints per unit product under agricultural intensification vary depending on the context, scale and accounting method. Life cycle analysis of footprints includes attributable emissions due to (i) land conversion (‘fixed cost’); (ii) external inputs used (‘variable cost’); (iii) crop production (‘agronomic efficiency’); and (iv) postharvest transport and processing (‘proportional’ cost). The interplay between fixed and variable costs results in a nuanced opportunity for intermediate levels of intensification to minimize footprints. The fertilizer level that minimizes the footprint may differ from the economic optimum. The optimization problem can be solved algebraically for quadratic crop fertilizer response equations. We applied this theory to data of palm oil production and fertilizer use from 23 plantations across the Indonesian production range. The current EU threshold requiring at least 35% emission saving for biofuel use can never be achieved by palm oil if produced: (i) on peat soils, or (ii) on mineral soils where the C debt due to conversion is larger than 20 Mg C ha−1, if the footprint is calculated using an emission ratio of N2O–N/N fertilizer of 4%. At current fertilizer price levels in Indonesia, the economically optimized N fertilizer rate is 344–394 kg N ha−1, while the reported mean N fertilizer rate is 141 kg N ha−1 yr−1 and rates of 74–277 kg N ha−1 would minimize footprints, for a N2O–N/N fertilizer ratio of 4–1%, respectively. At a C debt of 30 Mg C ha−1, these values are 200–310 kg N ha−1. Sustainable weighting of ecology and economics would require a higher fertilizer/yield price ratio, depending on C debt. Increasing production by higher fertilizer use from current 67% to 80% of attainable yields would not decrease footprints in current production conditions.
Break the pattern: breakpoints in beta diversity of vertebrates are general across clades and suggest common historical causes
Authors: Castro‐Insua Adrián , Gómez‐Rodríguez Carola , Baselga Andrés
Published: August 2016

The use of correlative analyses might be insufficient to understand the processes that control biodiversity, because the variables accounting for different hypotheses (e.g. current climate, past climate change, post‐glacial dispersal limitation) are mutually correlated. We suggest here that, in order to gain insight, it could be useful to search for latitudinal thresholds that could provide information about qualitative changes in the way biodiversity varies in space. Such tipping points could inform about higher‐level processes that are not reflected in correlative analyses. We test whether similar breakpoints in latitudinal beta‐diversity patterns exist for different vertebrate groups with diverse life histories and dispersal abilities. In birds, bats and non‐volant mammals we find breakpoints similar to those of amphibians. Differences in species composition are mainly due to species replacement from the equator to the breakpoint, but are dominated by nested species losses from the breakpoint to higher latitudes. Thus, marked thresholds discriminate two world regions where different processes appear to drive biodiversity.
Thrombospondin‐1 expression may be implicated in liver atrophic mechanism due to obstructed portal venous flow
Authors: Hayashi Hiromitsu , Kuroki Hideyuki , Higashi Takaaki , Takeyama Hideaki , Yokoyama Naomi , Okabe Hirohisa , Nitta Hidetoshi , Beppu Toru , Takamori Hiroshi , Baba Hideo
Published: August 2016

Aim

Liver is an amazing organ that can undergo regenerative and atrophic changes inversely, depending on blood flow conditions. Although the regenerative mechanism has been extensively studied, the atrophic mechanism remains to be elucidated.

Methods and Results

To assess the molecular mechanism of liver atrophy due to reduced portal blood flow, we analyzed the gene expressions between atrophic and hypertrophic livers induced by portal vein embolization in three human liver tissues using microarray analyses. Thrombospondin (TSP)‐1 is an extracellular protein and a negative regulator of liver regeneration through its activation of the transforming growth factor‐β/Smad signaling pathway. TSP‐1 was extracted as the most upregulated gene in atrophic liver compared to hypertrophic liver due to portal flow obstruction in human. Liver atrophic and hypertrophic changes were confirmed by HE and proliferating cell nuclear antigen staining and terminal deoxynucleotidyl transferase‐mediated digoxigenin‐dUTP nick‐end labeling. In an in vivo model with portal ligation, TSP‐1 and phosphorylated Smad2 expression were continuously induced at 6 h and thereafter in the portal ligated liver, whereas the induction was transient at 6 h in the portal non‐ligated liver. Indeed, while cell proliferation represented by proliferating cell nuclear antigen expression at 48 h was induced in the portal ligated liver, the sinusoidal dilatation and hepatocyte cell death with terminal deoxynucleotidyl transferase‐mediated digoxigenin‐dUTP nick‐end labeling was detectable at 48 h in the portal ligated liver.

Conclusions

Obstructed portal flow induces persistent TSP‐1 expression and transforming growth factor‐β/Smad signal activation in atrophic liver. Thrombospondin‐1 may be implicated in the liver atrophic change due to obstructed portal flow as a pro‐atrophic factor.
Liver stiffness measurement to platelet ratio index predicts the stage of liver fibrosis in non‐alcoholic fatty liver disease
Authors: Okajima Akira , Sumida Yoshio , Taketani Hiroyoshi , Hara Tasuku , Seko Yuya , Ishiba Hiroshi , Nishimura Takeshi , Umemura Atsushi , Nishikawa Taichiro , Yamaguchi Kanji , Moriguchi Michihisa , Mitsuyoshi Hironori , Yasui Kohichiroh , Minami Masahito , Itoh Yoshito
Published: August 2016

Aim

Platelet count and liver stiffness measurement (LSM) using transient elastography could identify significant fibrosis in patients with non‐alcoholic fatty liver disease (NAFLD). We constructed a novel index combining LSM with platelet count for staging fibrosis in Japanese patients with NAFLD.

Methods

We recruited 173 Japanese patients with liver biopsy‐proven NAFLD. The areas under the receiver operating characteristic curves were calculated and compared with established parameters and scoring systems for staging liver fibrosis.

Results

After excluding 10 patients in whom LSM failed, 163 patients with NAFLD were enrolled. The areas under the receiver operating characteristic curves of the LSM/platelet ratio (LPR) index for detecting fibrosis ≥stage 1, ≥stage 2, and ≥stage 3 were the greatest (0.835, 0.913, and 0.936, respectively) compared with those for various other parameters and established scoring systems, such as LSM, type IV collagen 7 s domain, platelet count, NAFIC score, fibrosis‐4 index, NAFLD fibrosis score, aspartate aminotransferase/alanine aminotransferase ratio, and aspartate aminotransferase to platelet ratio index. The optimal cut‐off, positive predictive, and negative predictive values of the LPR index for detecting ≥stage 3 fibrosis were 0.60, 48.9%, and 99.2%, whereas those of LSM were 10.0 kPa, 35.0%, and 99.0%, respectively. The novel LPR index helps avoid biopsies in a larger percentage of patients with NAFLD compared with that LSM alone.

Conclusions

The LPR index was the best predictor for staging fibrosis in patients with NAFLD. It represents a simple and non‐invasive alternative to liver biopsy in clinical practice.
Variations in stress and driving pore fluid pressure ratio using vein orientations along megasplay faults : Example from the Nobeoka Thrust, Southwest Japan
Authors: Otsubo Makoto , Miyakawa Ayumu , Kawasaki Ryoji , Sato Katsushi , Yamaguchi Asuka , Kimura Gaku
Published: August 2016

The Nobeoka Thrust of Southwest Japan is an on‐land example of an ancient megasplay fault that provides an excellent record of deformation and fluid flow at seismogenic depths. The present study reports: (i) temporal stress changes for the seismogenic period of the Nobeoka Thrust; and (ii) spatial heterogeneities in driving pressure ratios P* obtained from mineral veins around the Nobeoka Thrust fault zone. Many quartz veins that filled mode I cracks can be observed in the hanging wall and footwall of the thrust. Inversion for stress orientation suggests that normal faulting dominated in both the hanging wall and footwall, with similar stress axis orientations in both. The orientation of σ3 for the estimated stress regime is parallel to the slip direction of the Nobeoka Thrust. The detected normal‐faulting‐type stress regimes likely resulted from post‐seismic stress buildup after megathrust earthquakes. The hanging wall of the Nobeoka Thrust has smaller P* values than the footwall. Two possible explanations are proposed for the observed spatial variations in the driving pore fluid pressure ratio, P*: spatial variations in pore fluid pressure Pf are directly responsible for P* variations, or P* variations are controlled by differences in mechanical properties between the hanging wall and footwall.
Consensus on an Australian Nurse practitioner specialty framework using Delphi methodology: results from the CLLEVER 2 study
Authors: Helms Christopher , Gardner Anne , McInnes Elizabeth
Published: August 2016

Aim

The aim of this study was to achieve profession‐wide consensus on an Australian nurse practitioner specialty framework.

Background

Since its introduction in 1998, the Australian nurse practitioner profession has grown to over 1300 endorsed practitioners, representing over 50 different specialties. To complement better a generalist learning and teaching framework with specialist clinical education, prior research proposed a broad framework of Australian nurse practitioner specialty areas termed metaspecialties.

Design

This study employed an online three‐round modified Delphi method.

Method

Recruitment using purposive sampling and snowballing techniques identified an eligible sample from a population of nurse practitioners with at least 12 months’ postendorsement experience (n = 966). Data were collected using online survey software from September 2014–January 2015 and analysed using descriptive statistics and content analysis. The Content Validity Index and McNemar's Test for Change were used to determine consensus on the nurse practitioner metaspecialties.

Results

One‐fifth of the total eligible population completed the study. Participants achieved high consensus on four metaspecialties, including: Emergency and acute care, primary health care, child and family health care and mental health care. Two metaspecialties did not achieve consensus and require further investigation.

Conclusion

A large sample of nurse practitioners achieved consensus on an Australian metaspecialty framework, increasing the likelihood of widespread acceptance across the profession. This technique may be appropriate for use in jurisdictions with smaller populations of nurse practitioners. Ongoing research is needed to re‐evaluate the metaspecialties as the profession grows.
Advances in finding Alba: the locus affecting life history and color polymorphism in a Colias butterfly
Authors: Woronik A. , Wheat C. W.
Published: August 2016

Although alternative life‐history strategies exist within many populations, very little is known about their genetic basis and mechanistic insight into these traits could greatly advance the understanding of eco‐evolutionary dynamics. Many species of butterfly within the genus Colias exhibit a sex‐limited wing colour polymorphism, called Alba, which is correlated with an alternative life‐history strategy. Here, we have taken the first steps in localizing the region carrying Alba in Colias croceus, a species with no genomic resources, by generating whole genome sequence of a single Alba mother and two sequencing pools, one for her Alba and another for her orange, offspring. These data were used in a bulk‐segregant analysis wherein SNPs fulfilling the Mendelian inheritance expectations of Alba were identified. Then, using the conserved synteny in Lepidoptera, the Alba locus was assigned to chromosome 15 in Bombyx mori. We then identified candidate regions within the chromosome by investigating the distribution of Alba SNPs along the chromosome and the difference in nucleotide diversity in exons between the two pools. A region spanning ~ 5.7 Mbp at the 5′ end of the chromosome was identified as likely to contain the Alba locus. These insights set the stage for more detailed genomic scans and mapping of the Alba phenotype, and demonstrate an efficient use of genomic resources in a novel species.
Femtosecond laser cutting of human corneas for the subbasal nerve plexus evaluation
Authors: KOWTHARAPU B.S. , MARFURT C. , HOVAKIMYAN M. , WILL F. , RICHTER H. , WREE A. , STACHS O. , GUTHOFF R.F.
Published: August 2016

Assessment of various morphological parameters of the corneal subbasal nerve plexus is a valuable method of documenting the structural and presumably functional integrity of the corneal innervation in health and disease. The aim of this work is to establish a rapid, reliable and reproducible method for visualization of the human corneal SBP using femtosecond laser cut corneal tissue sections. Trephined healthy corneal buttons were fixed and processed using TissueSurgeon—a femtosecond laser based microtome, to obtain thick tissue sections of the corneal epithelium and anterior stroma cut parallel to the ocular surface within approximately 15 min. A near infrared femtosecond laser was focused on to the cornea approximately 70–90 μm from the anterior surface to induce material separation using TissueSurgeon. The obtained corneal sections were stained following standard immunohistochemical procedures with anti‐neuronal β‐III tubulin antibody for visualization of the corneal nerves. Sections that contained the epithelium and approximately 20–30 μm of anterior stroma yielded excellent visualisation of the SBP with minimal optical interference from underlying stromal nerves. In conclusion, the results of this study have demonstrated that femtosecond laser cutting of the human cornea offers greater speed, ease and reliability than standard tissue preparation methods for obtaining high quality thick sections of the anterior cornea cut parallel to the ocular surface.
Prenatal Depression Screening by Certified Nurse‐Midwives, Oregon
Authors: Rompala Kathryn S. , Cirino Nicole , Rosenberg Kenneth D. , Fu Rochelle , Lambert William E.
Published: August 2016

Introduction

About 18% of pregnant women have major or minor depression during pregnancy, but many are neither screened nor treated. Lack of treatment can have serious adverse consequences for the woman and her child. Since 2002, the American College of Nurse‐Midwives has advised midwives to integrate prevention, universal screening, treatment, and/or referral for depression into the care they provide. The American College of Obstetricians and Gynecologists’ 2015 guidelines recommend screening at least once in the perinatal period using a standardized, validated tool. A consensus has not been reached by professional organizations about the specifics of whether and when to screen for prenatal depression. The objective of this study is to understand the prenatal screening practices of midwives who practice in Oregon.

Methods

We surveyed all 162 Oregon‐licensed certified nurse‐midwives (CNMs). The survey asked about practice characteristics, demographics, screening, and perceived barriers to screening. The survey was administered electronically from October through December 2014.

Results

The response rate was 37%. Among the 53 CNM respondents who had provided prenatal care in the previous year, 50 (94%) reported screening for prenatal depression, and 38 (72%) reported the use of a standardized screening tool on more than 90% of prenatal patients. Thirty‐five (66%) CNMs reported using the Edinburgh Postnatal Depression Scale. More than 60% of respondents indicated that availability of mental health services and insurance constraints were barriers to screening.

Discussion

We explored prenatal depression screening practices of CNMs. Most Oregon CNMs use a standardized screening tool. We suggest 2 strategies to overcome barriers to screening: incorporation of a standardized screening tool into electronic medical records and negotiation with insurance companies. More research is needed to clarify when and how often pregnant women should be screened for depression and how to increase the number of women who receive treatment.
Brain repair and reprogramming: the route to clinical translation
Authors: Grealish S. , Drouin‐Ouellet J. , Parmar M.
Published: August 2016

The adult brain has a very limited capacity for generation of new neurons, and neurogenesis only takes place in restricted regions. Some evidence for neurogenesis after injury has been reported, but few, if any, neurons are replaced after brain injury or degeneration, and the permanent loss of neurons leads to long‐term disability and loss of brain function. For decades, researchers have been developing cell transplantation using exogenous cell sources for brain repair, and this method has now been shown to successfully restore lost function in experimental and clinical trials. Here, we review the development of cell‐replacement strategies for brain repair in Parkinson's disease using the example of human foetal brain cells being successfully translated from preclinical findings to clinical trials. These trials demonstrate that cell‐replacement therapy is a viable option for patients with Parkinson's disease, but more importantly also show how the limited availability of foetal cells calls for development of novel cell sources and methods for generating new neurons for brain repair. We focus on new stem cell sources that are on the threshold of clinical application for brain repair and discuss emerging cellular reprogramming technologies. Reviewing the current status of direct neural conversion, both in vitro and in vivo, where somatic cells are directly reprogrammed into functional neurons without passing through a stem cell intermediate, we conclude that both methods result in the successful replacement of new neurons that mature and integrate into the host brain. Thus, this new field shows great promise for future brain repair, although much work is still needed in preclinical animal models before it can be seriously considered for clinical applications.
At the interface of stem cell research and new technologies
Authors: Lendahl U.
Published: August 2016

Content List – Read more articles from the symposium: Human models and technology for regenerative medicine.
Limbic Pathway Correlates of Cognitive Impairment in Multiple Sclerosis
Authors: Keser Zafer , Hasan Khader M. , Mwangi Benson , Gabr Refaat E. , Steinberg Joel L. , Wilken Jeffrey , Wolinsky Jerry S. , Nelson Flavia M.
Published: August 2016

BACKGROUND AND PURPOSE

Distinct injuries to various limbic white matter pathways have been reported to be associated with different aspects of cognitive dysfunction in multiple sclerosis (MS). Diffusion tensor imaging (DTI) offers a noninvasive method to map tissue microstructural organization. We utilized quantitative magnetic resonance imaging methods to analyze the main limbic system—white matter structures in MS patients with cognitive impairment (CI).

METHODS

Ten cognitively nonimpaired MS (MSNI) patients and 36 patients with diagnosed CI (MSCI) underwent the minimal assessment of Cognitive Function in MS (MACFIMS) battery. DTI measures of fornix, cingulum, uncinate fasciculus (UF) included tract volume and corresponding fractional anisotropy (FA), mean (MD), axial (AD), and radial (AD) diffusivities. These were statistically analyzed for associations with CI after adjusting for the confounders.

RESULTS

Fornix FA and RD, left cingulum FA, MD, and RD, right cingulum FA, MD, and RD, and left UF FA showed significant differences between MSNI and MSCI (P< .001). Fornix FA (r= −.6) and RD (r= .52), and right cingulum FA (r= −.54) and RD (r= .5) correlated significantly with CI in regression analyses.

CONCLUSIONS

The extent of disruption of microstructural disorganization in the main limbic pathways using DTI impacts the extent of CI seen in subjects with MS.
Pathogenicity Variation and Population Genetic Structure of Plasmopara viticola in China
Authors: Li Xinlong , Yin Ling , Ma Lingjun , Zhang Yali , An Yunhe , Lu Jiang
Published: August 2016

Viticulture in China, like in many other major grape‐growing countries around the world, is severely affected by downy mildew (DM) disease caused by Plasmopara viticola (Pv). However, little has been known about the pathogenicity and genetic structure of the pathogen distributed in China. In this study, 206 single‐sporangiophore Pv strains were isolated from Pv‐infected leaves collected from the most important grape‐growing regions in China. Among them, 29 strains, isolated from a majority of sampled regions and from the hosts with different DM resistance, were tested for their pathogenicity by inoculating into six grape cultivars with different levels of DM resistance. Significant difference in pathogenicity was observed among these strains. Seven pairs of SSR primers selected from previous reports were used for genetic studies of these 206 Pv strains. A total of 64 alleles and 193 genotypes were identified, suggesting that oosporic infection resulted from sexual reproduction made the major contributions to the disease epidemics during the growing season. Analysis of molecular variance (AMOVA) and principal coordinate analysis (PCoA) showed that most of genetic variations were within populations. In addition, low levels of pairwise FST value (ranged from 0.02 to 0.07) and high levels of gene flow were detected between populations. Results from this study suggest that long‐distance dispersals of Pv oospore occur in China.