bluuebunny/crossref_metadata_2025 huggingface dataset:
Stable encoding of sounds over a broad range of statistical parameters in the auditory cortex
Authors: Blackwell Jennifer M. , Taillefumier Thibaud O. , Natan Ryan G. , Carruthers Isaac M. , Magnasco Marcelo O. , Geffen Maria N.
Published: December 2015

Natural auditory scenes possess highly structured statistical regularities, which are dictated by the physics of sound production in nature, such as scale‐invariance. We recently identified that natural water sounds exhibit a particular type of scale invariance, in which the temporal modulation within spectral bands scales with the centre frequency of the band. Here, we tested how neurons in the mammalian primary auditory cortex encode sounds that exhibit this property, but differ in their statistical parameters. The stimuli varied in spectro‐temporal density and cyclo‐temporal statistics over several orders of magnitude, corresponding to a range of water‐like percepts, from pattering of rain to a slow stream. We recorded neuronal activity in the primary auditory cortex of awake rats presented with these stimuli. The responses of the majority of individual neurons were selective for a subset of stimuli with specific statistics. However, as a neuronal population, the responses were remarkably stable over large changes in stimulus statistics, exhibiting a similar range in firing rate, response strength, variability and information rate, and only minor variation in receptive field parameters. This pattern of neuronal responses suggests a potentially general principle for cortical encoding of complex acoustic scenes: while individual cortical neurons exhibit selectivity for specific statistical features, a neuronal population preserves a constant response structure across a broad range of statistical parameters.
Conceptual grounding of language in action and perception: a neurocomputational model of the emergence of category specificity and semantic hubs
Authors: Garagnani Max , Pulvermüller Friedemann
Published: December 2015

Current neurobiological accounts of language and cognition offer diverging views on the questions of ‘where’ and ‘how’ semantic information is stored and processed in the human brain. Neuroimaging data showing consistent activation of different multi‐modal areas during word and sentence comprehension suggest that all meanings are processed indistinctively, by a set of general semantic centres or ‘hubs’. However, words belonging to specific semantic categories selectively activate modality‐preferential areas; for example, action‐related words spark activity in dorsal motor cortex, whereas object‐related ones activate ventral visual areas. The evidence for category‐specific and category‐general semantic areas begs for a unifying explanation, able to integrate the emergence of both. Here, a neurobiological model offering such an explanation is described. Using a neural architecture replicating anatomical and neurophysiological features of frontal, occipital and temporal cortices, basic aspects of word learning and semantic grounding in action and perception were simulated. As the network underwent training, distributed lexico‐semantic circuits spontaneously emerged. These circuits exhibited different cortical distributions that reached into dorsal‐motor or ventral‐visual areas, reflecting the correlated category‐specific sensorimotor patterns that co‐occurred during action‐ or object‐related semantic grounding, respectively. Crucially, substantial numbers of neurons of both types of distributed circuits emerged in areas interfacing between modality‐preferential regions, i.e. in multimodal connection hubs, which therefore became loci of general semantic binding. By relating neuroanatomical structure and cellular‐level learning mechanisms with system‐level cognitive function, this model offers a neurobiological account of category‐general and category‐specific semantic areas based on the different cortical distributions of the underlying semantic circuits.
Shift in interictal relative gamma power as a novel biomarker for drug response in two mouse models of absence epilepsy
Authors: Maheshwari Atul , Marks Rachel L. , Yu Katherine M. , Noebels Jeffrey L.
Published: December 2015

Objective

Two monogenic mouse models of childhood absence epilepsy, stargazer and tottering, differ strikingly in their response to N‐methyl‐d‐aspartate (NMDA) receptor blockade. We sought to evaluate the change in interictal relative gamma power as a reliable biomarker for this gene‐linked antiepileptic drug (AED) response.

Methods

The effects of AEDs on absolute and relative (to the total) power of frequencies between 2 and 300 Hz were analyzed within the interictal electroencephalogram (EEG) and correlated with antiseizure efficacy in awake behaving stargazer, tottering, and wild‐type (WT) littermate control mice.

Results

At baseline, we found a significant absolute as well as relative augmentation of 16–41 Hz power in stargazer compared to both tottering and WT mice. In stargazer, the NMDA receptor–antagonist MK‐801 (0.5 mg/kg) paradoxically exacerbates absence seizures but normalizes the augmented beta/gamma band of power to WT levels, suggesting that the elevation in 16‐ to 41‐Hz power is an NMDA receptor–mediated network property. In contrast, ethosuximide (200 mg/kg) and 4‐aminopyridine (2.5 mg/kg) reduce seizure activity and increase relative power within the gamma range in both stargazer and tottering mice. Intraperitoneal saline injection had no significant effect on either seizure frequency or relative gamma power. Along with results using carbamazepine and flupirtine, there was a strong inverse relationship between relative change in seizure duration and change in peak relative gamma power (r2 = 0.726).

Significance

In these two models of absence epilepsy, drugs that reduce relative gamma power are associated with an increase in seizures, whereas drugs that augment relative gamma power reduce seizures. Therefore, drug‐induced modulation of relative gamma power may serve as a biomarker for AED efficacy in absence epilepsy. Given the relationship between gamma power and fast‐spiking interneurons, these results also suggest that a drug's effect may in part be determined by its impact on specific inhibitory networks.
Influence of fire on woody vegetation density, cover and structure at Tiisa Kalahari Ranch in western Botswana
Authors: Mudongo Edwin , Fynn Richard , Bonyongo Mpaphi Casper
Published: December 2015

Woody vegetation assessments were conducted in the burned and unburned paddocks of Tiisa Kalahari Ranch in western Botswana to determine the influence of opportunistic burning on woody species density, cover and structure in semiarid rangelands. Burning was conducted by farm management twice in one paddock in October 2005 and 2006, and once in another paddock in October 2011 to control bush encroachment. Sampling was conducted in May 2012 using 50 by 2 m transects (16 at the 2011 burn site and 18 at the 2005/2006 burn site) as paired comparisons in both burned and unburned paddocks. Tree height was 0.27 m (28%) and 0.23 m (21%) lower (P < 0.05) in burned paddocks at the 2011 and 2005/2006 burn sites, respectively. There was an increase in the proportion of saplings and a decrease in tall woody plants in burned areas at all sites (P < 0.001). At the 2011 burn site, height and cover of Catophractes alexandri were 63% (P = 0.041) and 67% (P = 0.035) lower in burned paddocks, respectively. Density of Acacia mellifera was 53% (P = 0.031) lower, with more multi‐stemmed (>20 stems) plants in burned paddocks (P = 0.02). Grewia flava density was 59% higher in burned paddocks (P = 0.038). At the 2005/2006 burn site both height and density of Acacia hebeclada were significantly higher in burned paddocks (65%, P = 0.045 and 56%, P = 0.037, respectively). Tarchonanthus camphoratus was only present at this site, where its height, density and cover were significantly lower in burned paddocks (P < 0.05). Overall, tree height was shorter in burned than unburned paddocks, with C. alexandri contributing the most to the height reduction. Follow up browsing by goats on the coppice growth after burning may prevent C. alexandri, a dominant encroaching species from recruiting and spreading.
Cost‐effectiveness analysis of tenofovir/emtricitabine and abacavir/lamivudine in combination with efavirenz or atazanavir/ritonavir for treatment‐naïve adults withHIV‐1 infection in theUK, based on theAIDSClinical Trials Group 5202 clinical trial
Authors: Wilkins E , Fisher M , Brogan AJ , Talbird SE , La EM
Published: December 2015

Objectives

The aim of the study was to assess the cost‐effectiveness of the four regimens studied in theAIDSClinical Trials Group (ACTG) 5202 clinical trial, tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC) in combination with efavirenz (EFV) or atazanavir/ritonavir (ATV/r), for treatment‐naïve adults withHIV‐1 infection in theUK.

Methods

A Markov model with six health states based onCD4 cell count ranges was developed to predict long‐term costs and health outcomes for individuals on first‐line therapy. Head‐to‐head efficacy data comparingTDF/FTC + EFV,TDF/FTC + ATV/r,ABC/3TC + EFV, andABC/3TC + ATV/r were obtained fromACTG5202 for up to 192 weeks. Antiretroviral drug costs were based on current list prices. Other medical costs (2013UKpounds sterling), utility values, and mortality rates were obtained from published sources. Base‐case, sensitivity, and subgroup analyses (by baseline viral load) were conducted.

Results

Individuals usingTDF/FTC‐based regimens were predicted to remain on first‐line therapy longer and accrue more quality‐adjusted life‐years (QALYs) than individuals usingABC/3TC‐based regimens. At a willingness‐to‐pay threshold of £30 000 perQALYgained,TDF/FTC‐based regimens were predicted to be cost‐effective compared withABC/3TC‐based regimens, with incremental cost‐effectiveness ratios of £23 355 forTDF/FTC + EFVvs.ABC/3TC + EFVand £23 785 forTDF/FTC + ATV/rvs.ABC/3TC + ATV/r. Results were generally robust in subgroup, sensitivity, and scenario analyses.

Conclusions

In an analysis of the regimens studied inACTG5202 for treatment‐naïve adults withHIV‐1 infection in theUK,TDF/FTC‐based regimens yielded more favourable health outcomes and were generally predicted to be cost‐effective compared withABC/3TC‐based regimens. These results confirm thatTDF/FTC‐based regimens are not only clinically effective but also cost‐effective.
German Public Finances through the Financial Crisis
Authors: Blömer Maximilian J. , Dolls Mathias , Fuest Clemens , Löffler Max , Peichl Andreas
Published: December 2015

The German experience of the financial crisis was very different from that of most other European countries. Germany was hit by a very strong shock that was relatively concentrated in the exporting, manufacturing industries. In addition, the German labour market was very resilient during the crisis due to earlier labour market reforms and policy instruments facilitating labour hoarding. As a consequence, the public finances were only moderately affected and not many policy reforms had to be enacted. This paper presents the German experience of the financial crisis. We start by presenting the macroeconomic situation and how the crisis unfolded in Germany, before focusing on the situation of the public finances. Finally, we analyse the policy responses to the financial crisis.
UK Public Finances: From Crisis to Recovery
Authors: Emmerson Carl , Tetlow Gemma
Published: December 2015

The financial crisis of 2008 and associated recession caused significant permanent damage to the UK's public finances: the UK economy is not expected to regain the economic growth trajectory that was predicted pre‐crisis. In response, UK governments have planned and (so far, partially) implemented a significant fiscal tightening to cut borrowing from a post‐war high of over 10 per cent of GDP to a planned overall surplus. This fiscal tightening is heavily weighted towards spending cuts, which are expected to comprise 86 per cent of the measures. The spending measures imply not only a significant reduction in spending as a share of GDP but also a significant change in the composition of that spending – with benefits for pensioners, health care and schooling now taking up a much larger share of overall spending than they did pre‐crisis. Overall, the new tax and benefit measures have included some welcome improvements to the structure of the system, but many of these have probably happened in spite of, rather than because of, the need for fiscal consolidation. Opportunities to make many significant improvements have been missed, while in other areas new policies have made the system less efficient and less coherent.
Irish Public Finances through the Financial Crisis
Authors: Keane Claire
Published: December 2015

Ireland was one of the countries most negatively affected by the Great Recession. GDP fell by 13 per cent and unemployment rates increased sharply. The recession uncovered fundamental flaws in the Irish economy such as an over‐reliance on the construction sector for employment and taxes and a move away from income‐based taxes. A collapse in house prices and a sharp reduction in construction activity led to job losses and falls in the tax take. Irish banks had become over‐reliant on foreign funds to finance lending and regulation was lax. The bursting of the construction bubble was therefore coupled with a financial crisis resulting in a ‘bailout’ of Irish banks by the government. As the gap between revenue and expenditure grew and borrowing increased, a government‐backed guarantee of Irish bank deposits eventually led to worries about the solvency of the Irish government and the inability to borrow in international bond markets. This resulted in Ireland entering into a financial assistance programme with the International Monetary Fund (IMF), the European Union (EU) and the European Central Bank (ECB). The government embarked on a series of austerity measures amounting to one‐fifth of GDP between 2008 and 2015, with roughly one‐third of the response being increased taxes and two‐thirds expenditure reductions. Taxes have increased, a residential property tax was introduced and social welfare rates have been reduced for those of working age. The redistributive effects of these changes cannot be viewed as either regressive or progressive, with the top decile experiencing the sharpest cut to disposable income, followed by the bottom decile. Recovery has been strong in recent years, however, with GDP forecast to return to its 2007 peak level in 2015. The unemployment rate has fallen to just under 10 per cent from its 2011 peak of 15 per cent but still remains well above its pre‐crisis level of 4 per cent.
European Public Finances and the Great Recession: France, Germany, Ireland, Italy, Spain and the United Kingdom Compared
Authors: Bozio Antoine , Emmerson Carl , Peichl Andreas , Tetlow Gemma
Published: December 2015

We compare economic trends over the financial crisis, and the tax and benefit reforms implemented in response, across six EU countries. Countries where the crisis led to a relatively greater increase in public spending than a decline in tax revenues – in particular, France and Italy – are found to have implemented consolidations that are more reliant on tax increases than spending cuts. While in France and Italy households with children have lost less from tax and benefit reforms than pensioner households, the reverse is true in Ireland and the United Kingdom. The pattern of cuts to public services also varies: France, Ireland and the UK chose to protect spending on health and schools from cuts, while Italy and Spain chose to cut spending on these services relatively deeply. One clear improvement has been the introduction of greater independence and transparency in the production of economic and fiscal forecasts. Unfortunately, in many cases, the fiscal response to the crisis missed opportunities to improve the overall efficiency of the tax system.
Spanish Public Finances through the Financial Crisis
Authors: Martí Francisco , Pérez Javier J.
Published: December 2015

Spain's public finances have been under significant stress during the financial crisis, despite pre‐crisis fiscal surpluses and low levels of public debt. The impact of the crisis and an initial phase of countercyclical activism exacerbated the existing (structural) fiscal vulnerabilities. To correct the fiscal imbalances, a significant number of bold policy actions were taken, affecting taxation, public spending, national fiscal rules and the structure of the public sector. In this paper, we discuss the evolution of the public finances in Spain through the financial crisis, framing crisis‐related fiscal policy measures within medium‐term economic trends and focusing on policy responses to the crisis. We also touch upon the main policy challenges ahead.
On ‘Modal Personism’
Authors: McMahan Jeff
Published: December 2015

In this article I present several challenges to the view that Shelly Kagan calls ‘modal personism’. First, there is a plausible account of our identity that, if true, greatly diminishes the scope of Kagan's view. But the scope of the view is already quite limited because the category of modal persons is restricted to those non‐persons that had but have lost the potential to become persons. If the category were to include non‐persons that retain the potential to become persons, Kagan's view would have implausible implications about abortion and about the moral status of certain animals.
What the Old Right of Necessity Can Do for the Contemporary Global Poor
Authors: Mancilla Alejandra
Published: December 2015

Given the grim global statistics of extreme poverty and socioeconomic inequalities, moral and political philosophers have focused on the duties of justice and assistance that arise therefrom. What the needy are morally permitted to do for themselves in this context has been, however, a mostly overlooked question. Reviving a medieval and early modern account of the right of necessity, I propose that a chronically deprived agent has a right to take, use and/or occupy whatever material resources are required to guarantee her self‐preservation, or the means necessary to acquire them. There are three individually necessary and jointly sufficient conditions: the need is basic, the claimant does not violate other equally important moral interests, and it is a last resort. I present two recommendations to be followed by the claimants, and offer some examples where this principle may be applied today. I reply to the objections that understanding the right of necessity in this way kills its intuitive plausibility, and that it is a remedy worse than the disease. I conclude that, while not the best solution for the problem of global poverty, the exercise of this right should be accepted if we believe in the human right to subsistence.
Secukinumab treatment of plaque psoriasis shows early improvement in DLQI response – results of a phase II regimen‐finding trial
Authors: Augustin M. , Abeysinghe S. , Mallya U. , Qureshi A. , Roskell N. , McBride D. , Papavassillis C. , Gelfand J.
Published: December 2015

Background

The social stigma and chronicity of psoriasis significantly affect health‐related quality of life (HRQoL).

Objective

We examined the effect of three regimens of secukinumab on HRQoL in moderate to severe psoriasis patients.

Methods

Twelve‐week data from a phase II, randomized, double‐blind, placebo‐controlled, regimen‐finding study evaluated HRQoL, measured by the Dermatology Life Quality Index (DLQI). Secukinumab or placebo was administered subcutaneously in three treatment regimens: single (baseline only), monthly (baseline, weeks 4, 8) and early (baseline, weeks 1, 2, 4). Differences among regimens were assessed with logistic regression models and Fisher's exact test.

Results

Patients (n = 404) were randomized to single (baseline) treatment regimen, n = 66; monthly, (baseline, weeks 4 and 8), n = 138; early, (baseline, weeks 1, 2, 4), n = 133; and placebo, n = 67. DLQI response was significantly higher in early, monthly and single regimens than in placebo regimen (40.8%, 33.6% and 13.1% vs. 1.6%, respectively; P < 0.001 for all).

Conclusion

Moderate to severe psoriasis patients receiving monthly and early treatment with secukinumab demonstrated improved HRQoL compared with placebo.
Risk profiles of neurosyphilis in HIV‐negative patients with primary, secondary and latent syphilis: implications for clinical intervention
Authors: Shi M. , Peng R.‐R. , Gao Z. , Zhang S. , Lu H. , Guan Z. , Gao Y. , Wang C. , Zhou P.
Published: December 2015

Background

Neurosyphilis is one of the most feared complications of syphilis. The question of how to identify patients at higher risk in order for timely intervention whilst avoiding unnecessary lumbar puncture remains.

Methods

Between August 2009 and March 2013, a total of 834 HIV‐negative patients with primary, secondary or latent syphilis were recruited. Venous blood and cerebrospinal fluid specimens were collected for diagnoses of syphilis and/or neurosyphilis and information of socio‐demographic and behavioral characteristics was collected by interviewing with a questionnaire.

Results

The prevalence of neurosyphilis differed among patients with primary (7.1%), secondary (23.8%) and latent (26.6%) syphilis. Neurosyphilis was more likely in male patients (1.52‐fold). Compared with patients aged <30 years, those aged 45–59 years and ≥60 years old had a 2.51‐fold and 4.98‐fold risk of neurosyphilis respectively. Male gender and age ≥45 years were consistently associated with neurosyphilis both in secondary and latent stage. There was a 2.68‐fold, 2.55‐fold and 3.67‐fold increased risk of neurosyphilis when the serum RPR titer was 1:32, 1:64 and ≥1:128 compared to that of ≤1:16. ).

Conclusions

Male gender and age 45years are both correlated risk factors for neurosyphilis in HIV‐negative patients with primary, secondary and latent syphilis.
Peer Evaluation: Incentives and Coworker Relations
Authors: Sol Joeri
Published: December 2015

In many workplaces, coworkers have the best information about each other's efforts. This paper studies a principal who only observes the joint output by two limitedly liable agents, while agents receive signals about each other's effort levels. The principal attempts to exploit this information through peer evaluation; agents are asked to report their signal and may receive a bonus for being evaluated positively. Lying aversion ascertains that truthful evaluation is possible, while interpersonal relations between colleagues give an incentive to misreport. This paper shows that peer evaluation gives an incentive for effort, even when the evaluations are not truthful. The peer evaluation bonus is constrained by more intensive coworker relations. Still, the optimal contract always includes a peer evaluation bonus, sometimes complemented with a team bonus. Coworker relations have nonmonotonic effects on profits in the optimal contract.
Older Adults Reporting More Diabetes Mellitus Care Have Greater 9‐Year Survival
Authors: Han Benjamin H. , Blaum Caroline S. , Ferris Rosie E. , Min Lillian C. , Lee Pearl G.
Published: December 2015

Objectives

To determine whether receiving more recommended diabetes mellitus (DM) care processes (tests and screenings) would translate into better 9‐year survival for middle‐aged and older adults.

Design

Longitudinal mortality analysis using the Health and Retirement Study Diabetes Mailout Survey.

Setting

Health and Retirement Study (HRS).

Participants

Individuals aged 51 and older (n = 1,879; mean age 68.8 ± 8.7, 26.5% aged ≥75) with self‐reported DM who completed the Diabetes Mailout Survey and the core 2002 HRS survey.

Measurements

A composite measure of five self‐reported diabetes mellitus care process measures were dichotomized as greater (3–5 processes) versus fewer (0–2 processes) care processes provided. Cox proportional hazards models were used to test relationships between reported measures and mortality, controlling for sociodemographic characteristics, function, comorbidities, geriatric conditions, and insulin use.

Results

Prevalence of self‐reported care processes was 80.1% for glycosylated hemoglobin test, 75.9% for urine test, 67.5% for eye examination, 67.7% for aspirin counseling, and 48.2% for diabetes education. In 9 years, 32.1% respondents died. Greater care correlated with 24% lower risk of dying (adjusted hazard ratio = 0.76, 95% confidence interval = 0.64–0.91) at 9‐year follow up. When respondents were age‐stratified (≥75 vs <75) longer survival was statistically significant only in the older age group.

Conclusion

Although it is not possible to account for differences in adherence to care that may also affect survival, this study demonstrates that monitoring of and counseling about types of DM care processes are associated with long‐term survival benefit even in individuals aged 75 and older with DM.
The definitions of three‐dimensional landmarks on the human face: an interdisciplinary view
Authors: Katina Stanislav , McNeil Kathryn , Ayoub Ashraf , Guilfoyle Brendan , Khambay Balvinder , Siebert Paul , Sukno Federico , Rojas Mario , Vittert Liberty , Waddington John , Whelan Paul F. , Bowman Adrian W.
Published: December 2015

The analysis of shape is a key part of anatomical research and in the large majority of cases landmarks provide a standard starting point. However, while the technology of image capture has developed rapidly and in particular three‐dimensional imaging is widely available, the definitions of anatomical landmarks remain rooted in their two‐dimensional origins. In the important case of the human face, standard definitions often require careful orientation of the subject. This paper considers the definitions of facial landmarks from an interdisciplinary perspective, including biological and clinical motivations, issues associated with imaging and subsequent analysis, and the mathematical definition of surface shape using differential geometry. This last perspective provides a route to definitions of landmarks based on surface curvature, often making use of ridge and valley curves, which is genuinely three‐dimensional and is independent of orientation. Specific definitions based on curvature are proposed. These are evaluated, along with traditional definitions, in a study that uses a hierarchical (random effects) model to estimate the error variation that is present at several different levels within the image capture process. The estimates of variation at these different levels are of interest in their own right but, in addition, evidence is provided that variation is reduced at the observer level when the new landmark definitions are used.
Infrahepatic inferior caval and azygos vein formation in mammals with different degrees of mesonephric development
Authors: Hikspoors Jill P. J. M. , Mekonen Hayelom K. , Mommen Greet M. C. , Cornillie Pieter , Köhler S. Eleonore , Lamers Wouter H.
Published: December 2015

Controversies regarding the development of the mammalian infrahepatic inferior caval and azygos veins arise from using topography rather than developmental origin as criteria to define venous systems and centre on veins that surround the mesonephros. We compared caudal‐vein development in man with that in rodents and pigs (rudimentary and extensive mesonephric development, respectively), and used Amira 3D reconstruction and Cinema 4D‐remodelling software for visualisation. The caudal cardinal veins (CCVs) were the only contributors to the inferior caval (IVC) and azygos veins. Development was comparable if temporary vessels that drain the large porcine mesonephros were taken into account. The topography of the CCVs changed concomitant with expansion of adjacent organs (lungs, meso‐ and metanephroi). The iliac veins arose by gradual extension of the CCVs into the caudal body region. Irrespective of the degree of mesonephric development, the infrarenal part of the IVC developed from the right CCV and the renal part from vascular sprouts of the CCVs in the mesonephros that formed ‘subcardinal’ veins. The azygos venous system developed from the cranial remnants of the CCVs. Temporary venous collaterals in and around the thoracic sympathetic trunk were interpreted as ‘footprints’ of the dorsolateral‐to‐ventromedial change in the local course of the intersegmental and caudal cardinal veins relative to the sympathetic trunk. Interspecies differences in timing of the same events in IVC and azygos‐vein development appear to allow for proper joining of conduits for caudal venous return, whereas local changes in topography appear to accommodate efficient venous perfusion. These findings demonstrate that new systems, such as the ‘supracardinal’ veins, are not necessary to account for changes in the course of the main venous conduits of the embryo.
Is THEREAN OPTIMAL PENSION FUND SIZE? A SCALE‐ECONOMY ANALYSISOF ADMINISTRATIVE COSTS
Authors: Bikker Jacob A.
Published: December 2015

ABSTRACT

This article investigates scale economies and the optimal scale of pension funds, estimating different cost functions with varying assumptions about the shape of the underlying average cost function: U‐shaped versus monotonically declining. Using unique data for Dutch pension funds over 1992–2009, we find that unused scale economies for both administrative activities are indeed large and concave, that is, huge for small pension funds and decreasing with pension fund size. We observe a clear optimal scale of around 40,000 participants during 1992–2000 (pointing to a U‐shaped average cost function), which increases in subsequent years to size above the largest pension fund, pointing to monotonically decreasing average costs. These model‐based outcomes are roughly in line with the results of a survivorship analysis.
THE ROLE OF PREGNANCY IN MICRO HEALTH INSURANCE: EVIDENCE OF ADVERSE SELECTION FROM PAKISTAN
Authors: Yao Yi , Schmit Joan T. , Sydnor Justin R.
Published: December 2015

ABSTRACT

With increasing interest from commercial players in developing insurance markets to meet the needs of low‐income people, efforts to find sustainable products have expanded rapidly yet remain elusive. This is particularly true in the domain of health insurance, where the general challenges of offering voluntary private health insurance are often exacerbated by poor underlying health services and a lack of public health programs. In an effort to identify new opportunities to expand health insurance protection to underserved markets, we analyze a rich data set from a micro health insurance program in Pakistan. Observing that pregnancy‐related care accounts for 40 percent of all claims and 36 percent of the total claims amount, we focus much of our attention on understanding the role of pregnancy in micro health insurance. We find evidence of extensive adverse selection related to pregnancy claims, both with regard to original coverage purchase and with regard to renewal. In many countries, pregnancy health care is provided by or paid for by the government. We encourage consideration of this possibility, leaving the remaining health care needs for market‐based health insurance.
Nonmimetic Knowledge and Innovation Performance: Empirical Evidence from Developing Countries
Authors: Wang Tang , Libaers Dirk
Published: December 2015

The knowledge‐based view suggests that the innovative performance of a firm is a function of the utilization and recombination of internal and external knowledge. The process of knowledge utilization and recombination to create new products can occur internally, through research and development activities, as well as externally, by making investments in creating links with suppliers, universities, customers, and a wide range of actors in the innovation system. This study focuses on the impact of unique, nonmimetic external knowledge, which is defined as unique technological knowledge that is not tapped by other firms in the new venture's operating environment, on the new venture's innovative performance. The purpose of the research is to investigate whether firms really benefit from utilizing and recombining unique, nonmimetic knowledge in creating innovative products in a developing country context. Drawing on the knowledge‐based view and institutional theory, this study argues that entrepreneurs in their utilization and recombination of unique, nonmimetic knowledge are not always successful at creating new products. The empirical context is drawn from the Enterprise Survey produced by the Investment Climate Group of the World Bank. The findings based on a large sample of new ventures in developing countries reveal a curvilinear relationship with marginal diminishing returns between the degree of unique, nonmimetic knowledge and innovative performance. The results also show significant moderating effects of strategic product planning and economic and regulatory policy uncertainty. Specifically, strategic product planning helps in converting very unique, nonmimetic knowledge into new products. In addition, policy uncertainty can also positively moderate the process of recombining and converting unique, nonmimetic knowledge into new products. This study provides a more complete account of how unique, nonmimetic external knowledge affects innovative performance of new ventures in developing countries.
Comparative quantitative assessment of global small bowel motility using magnetic resonance imaging in chronic intestinal pseudo‐obstruction and healthy controls
Authors: Menys A. , Butt S. , Emmanuel A. , Plumb A. A. , Fikree A. , Knowles C. , Atkinson D. , Zarate N. , Halligan S. , Taylor S. A.
Published: December 2015

Background

Chronic intestinal pseudo‐obstruction (CIPO) is characterized by dilatation of the bowel lumen and abnormal motility. In this study, we aimed to quantify small bowel dysmotility in CIPO using a validated pan‐intestinal motility assessment technique based on motion capture magnetic resonance imaging (MRI) compared to normal controls. In addition, we explored if motility responses of CIPO patients to neostigmine challenge differed from healthy volunteers.

Methods

Twenty healthy volunteers (mean age 28, range 22–48) and 11 CIPO patients (mean age 47, range 19–90) underwent MRI enterography to capture global small bowel motility. Eleven controls and seven CIPO patients further underwent a randomized placebo‐controlled crossover study of either intravenous neostigmine (0.5 mg) or saline with motility MRI repeated at a mean of 3 weeks. Motility was quantified in regions of interest placed to encompass the whole small bowel volume using a validated, postprocessing technique to give a global motility index in arbitrary units (AU). Baseline and stimulated motility was compared using Wilcoxon rank–sum paired T‐tests.

Key Results

Baseline global small bowel motility was significantly lower in CIPO patients compared to controls (mean 0.25 AU vs 0.35 AU, p < 0.001). Motility in both groups increased significantly after neostigmine (0.06 AU increase, p = 0.016 in CIPO and 0.06 AU increase, p = 0.002 in controls). Three patients with scleroderma had a reduced response to neostigmine.

Conclusions & Inferences

Global small bowel motility in CIPO patients is significantly lower than controls and response to the pro‐kinetic agent neostigmine may differ according to disease phenotype. Software‐quantified bowel motility using cine MRI has potential as a future tool to investigate enteric dysmotility.
First report of an Asian family with hemoglobin Evans [α2 62 (E11) Val → Met]
Authors: Ishimaru Sae , Saito Yuya , Yokokawa Yuichi , Yuza Yuki , Kaneko Takashi
Published: December 2015

Hemoglobin Evans is an unstable variant caused by a single nucleotide mutation that produces a valine‐to‐methionine substitution at residue 62 of the α‐globin chain. It has not been reported in the Asian population and only three cases have been reported worldwide. We diagnosed a Japanese boy with chronic hemolytic anemia with hemoglobin Evans after genetic testing. This is the first familial case of hemoglobin Evans in an Asian population.
Long‐term UVA eye irradiation causes decreased learning ability in mice
Authors: Hiramoto Keiichi , Kasahara Emiko
Published: December 2015

Background

Long‐term eye radiation with ultraviolet A (UVA) denatures the cells of the cerebral hippocampus. However, the influence on memory and learning ability in mice is not known.

Methods

HR‐1 mice were used. We irradiated the eyes or dorsal skin of the mice with UVA at a dose of 110 kJ/m2 using an FL20SBLB‐A lamp for 6, 12, and 24 months.

Results

The mean escape latency in the water maze was significantly increased in the UVA‐irradiated mice in comparison with that seen in the controls. In the mice in which UVA eye irradiation was performed for 24 months, the depression of memory and learning ability was remarkable. The acetylcholinesterase activity, choline acetyltransferase activity, and acetylcholine content in the brain in the UVA eye‐irradiated mice were significantly less than those observed in the control mice. Furthermore, during UVA eye irradiation, the levels of β‐amyloid (Aβ), γ‐secretase, which produces Aβ peptide, and advanced glycation end products increased. Moreover, the effects of UVA eye irradiation increased with the duration of irradiation (or aging), and the introduction of glucose into the brain also decreased with UVA eye irradiation.

Conclusions

These results indicate that UVA eye irradiation induces a decreased memory and learning ability in mice.
ABCB19‐mediated polar auxin transport modulates Arabidopsis hypocotyl elongation and the endoreplication variant of the cell cycle
Authors: Wu Guosheng , Carville Jacqueline S. , Spalding Edgar P.
Published: December 2015

Elongation of the Arabidopsis hypocotyl pushes the shoot‐producing meristem out of the soil by rapid expansion of cells already present in the embryo. This elongation process is shown here to be impaired by as much as 35% in mutants lacking ABCB19, an ATP‐binding cassette membrane protein required for polar auxin transport, during a limited time of fast growth in dim white light beginning 2.5 days after germination. The discovery of high ectopic expression of a cyclin B1;1‐based reporter of mitosis throughout abcb19 hypocotyls without an equivalent effect on mitosis prompted investigations of the endoreplication variant of the cell cycle. Flow cytometry performed on nuclei isolated from upper (growing) regions of 3‐day‐old hypocotyls showed ploidy levels to be lower in abcb19 mutants compared with wild type. CCS52A2 messenger RNA encoding a nuclear protein that promotes a shift from mitosis to endoreplication was lower in abcb19 hypocotyls, and fluorescence microscopy showed the CCS52A2 protein to be lower in the nuclei of abcb19 hypocotyls compared with wild type. Providing abcb19 seedlings with nanomolar auxin rescued their low CCS52A2 levels, endocycle defects, aberrant cyclin B1;1 expression, and growth rate defect. The abcb19‐like growth rate of ccs52a2 mutants was not rescued by auxin, placing CCS52A2 after ABCB19‐dependent polar auxin transport in a pathway responsible for a component of ploidy‐related hypocotyl growth. A ccs52A2 mutation did not affect the level or pattern of cyclin B1;1 expression, indicating that CCS52A2 does not mediate the effect of auxin on cyclin B1;1.
SUMOylation represses SnRK1 signaling in Arabidopsis
Authors: Crozet Pierre , Margalha Leonor , Butowt Rafal , Fernandes Noémia , Elias Carlos A. , Orosa Beatriz , Tomanov Konstantin , Teige Markus , Bachmair Andreas , Sadanandom Ari , Baena‐González Elena
Published: December 2015

The SnRK1 protein kinase balances cellular energy levels in accordance with extracellular conditions and is thereby key for plant stress tolerance. In addition, SnRK1 has been implicated in numerous growth and developmental processes from seed filling and maturation to flowering and senescence. Despite its importance, the mechanisms that regulate SnRK1 activity are poorly understood. Here, we demonstrate that the SnRK1 complex is SUMOylated on multiple subunits and identify SIZ1 as the E3 Small Ubiquitin‐like Modifier (SUMO) ligase responsible for this modification. We further show that SnRK1 is ubiquitinated in a SIZ1‐dependent manner, causing its degradation through the proteasome. In consequence, SnRK1 degradation is deficient in siz1‐2 mutants, leading to its accumulation and hyperactivation of SnRK1 signaling. Finally, SnRK1 degradation is strictly dependent on its activity, as inactive SnRK1 variants are aberrantly stable but recover normal degradation when expressed as SUMO mimetics. Altogether, our data suggest that active SnRK1 triggers its own SUMOylation and degradation, establishing a negative feedback loop that attenuates SnRK1 signaling and prevents detrimental hyperactivation of stress responses.
A comparative study of epidermal tight junction proteins in a dog model of atopic dermatitis
Authors: Kim Ha‐Jung , Cronin Megan , Ahrens Kim , Papastavros Vassi , Santoro Domenico , Marsella Rosanna
Published: December 2015

Background

Tight junctions (TJ) are important for skin barrier function and could be relevant in modulating allergen penetration in atopic dermatitis (AD). Humans with AD have been described to have decreased expressions of some TJ proteins in the skin.

Hypothesis/Objectives

This study aimed to investigate TJ protein expression using an experimental AD model in dogs.

Methods

Skin biopsies from six atopic (nonlesional skin) and five normal beagle dogs were stained for TJ proteins [zonula occludens 1 (ZO‐1), occludin, claudin‐1] by immunohistochemistry. Staining intensity was evaluated both objectively using imaging software and subjectively. Six images/sections were randomized and blindly scored by six investigators for intensity, distribution, integrity and staining pattern.

Results

The intensity of ZO‐1 was significantly decreased in the atopic group objectively (P = 0.010) and subjectively (P = 0.002) relative to the normal group. Occludin was decreased significantly subjectively (P = 0.027) but not objectively. Claudin was not significantly different between groups by either quantification. Additionally, only ZO‐1 demonstrated a significantly patchier staining pattern in the atopic group. There was no consistent staining pattern in this study.

Conclusions and clinical importance

ZO‐1 and occludin, which have not been described to be associated with the development of AD in humans, could play a role in this atopic dog model. Further investigation on the expression and modulation of TJ proteins and their clinical relevance is needed.
Repeated oral dose tolerance in dogs treated concomitantly with ciclosporin and oclacitinib for three weeks
Authors: Panteri Alessandro , Strehlau Günther , Helbig Rainer , Prost Christine , Doucette Kelly
Published: December 2015

Background

Ciclosporin and oclacitinib are immunomodulators approved for the treatment of canine atopic dermatitis. The administration of a short course of prednisolone at the beginning of ciclosporin therapy hastens the efficacy of this drug; oclacitinib has a rapid antipruritic effect similar to that of prednisolone.

Objectives

To evaluate the oral tolerance of oclacitinib and ciclosporin given concurrently for three weeks.

Animals

Two groups of eight beagles.

Methods

Dogs were randomized to receive oclacitinib alone (0.4–0.6 mg/kg twice daily for 14 days then once daily for seven days) or in combination with ciclosporin (5 mg/kg once daily) for three weeks. They were examined every day and adverse events were recorded. Blood samples were collected during the acclimatization phase, weekly during treatment and at the end of the study for haematology, clinical chemistry and coagulation evaluation.

Results

There were no abnormal clinical observations following treatment with oclacitinib given alone or concomitantly with ciclosporin, with the exception of diarrhoea in two dogs receiving both drugs. Three dogs from each group experienced transient inappetence; three dogs treated with oclacitinib had mild weight loss. Clinical pathology parameters remained within the reference range for beagle dogs at that facility.

Conclusions and clinical importance

The concomitant administration of ciclosporin and oclacitinib for three weeks to beagles was well tolerated and was not associated with an increase in the number of adverse events or laboratory abnormalities beyond those associated with oclacitinib given alone.
Luces y sombras de la comunicación del Real Madrid CF. Reflexiones desde el periodismo deportivo
Authors: Olabe Sánchez Fernando
Published: December 2015

La influencia en el entorno, las exigencias financieras y una concepción global de la gestión empresarial han originado un cambio en el modelo comunicativo del Real Madrid CF, en lo tocante a su relación con sus stakeholders y en especial con los periodistas deportivos. Se aplicó una metodología cualitativa, una revisión bibliográfica y de información secundaria de fuentes y entrevistas mediante cuestionario a periodistas que cubren la información del club.

Los resultados muestran que la gestión comunicativa del club equipara a los periodistas con otros públicos objetivos y que el Departamento de Comunicación se ha convertido en un mecanismo de control que limita el acceso a la información, fiscaliza la información dirigida a los medios y entorpece la labor de los periodistas.

En consecuencia, advertimos que las relaciones personales entre ambos actores se han deteriorado y que el comportamiento comunicativo del Club se homogeneiza con sus homólogos de otras competiciones europeas.
An Analytical Foundation for Optimal Compensation of Three-Dimensional Shape Deformation in Additive Manufacturing
Authors: Huang Qiang
Published: December 2015

Additive manufacturing (AM) or three-dimensional (3D) printing is a promising technology that enables the direct fabrication of products with complex shapes without extra tooling and fixturing. However, control of 3D shape deformation in AM built products has been a challenging issue due to geometric complexity, product varieties, material phase changing and shrinkage, and interlayer bonding. One viable approach for accuracy control is through compensation of the product design to offset the geometric shape deformation. This work provides an analytical foundation to achieve optimal compensation for high-precision AM. We first present the optimal compensation policy or the optimal amount of compensation for two-dimensional (2D) shape deformation. By analyzing its optimality property, we propose the minimum area deviation (MAD) criterion to offset 2D shape deformation. This result is then generalized by establishing the minimum volume deviation (MVD) criterion and by deriving the optimal amount of compensation for 3D shape deformation. Furthermore, MAD and MVD criteria provide convenient quality measure or quality index for AM built products that facilitate online monitoring and feedback control of shape geometric accuracy.
Structural and growth aspects of electron beam physical vapor deposited NiO-CeO2 nanocomposite films
Authors: Kuanr Sushil Kumar , K Suresh Babu
Published: December 2015

Deposition of composite materials as thin film by electron beam physical vapor deposition technique (EB-PVD) still remains as a challenge. Here, the authors report the deposition of NiO-CeO2 (30/70 wt. %) composites on quartz substrate by EB-PVD. Two NiO-CeO2 nanocomposite targets—one as green compact and the other after sintering at 1250 °C—were used for the deposition. Though the targets varied with respect to physical properties such as crystallite size (11–45 nm) and relative density (44% and 96%), the resultant thin films exhibited a mean crystallite size in the range of 20–25 nm underlining the role of physical nature of deposition. In spite of the crystalline nature of the targets and similar elemental concentration, a transformation from amorphous to crystalline structure was observed in thin films on using sintered target. Postannealing of the as deposited film at 800 °C resulted in a polycrystalline structure consisting of CeO2 and NiO. Deposition using pure CeO2 or NiO as target resulted in the preferential orientation toward (111) and (200) planes, respectively, showing the influence of adatoms on the evaporation and growth process of NiO-CeO2 composite. The results demonstrate the influence of electron beam gun power on the adatom energy for the growth process of composite oxide thin films.