bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apparent subadditivity of the efficacy of initial combination treatments for type 2 diabetes is largely explained by the impact of baseline HbA1c on efficacy
Authors: Polidori D. , Capuano G. , Qiu R. 
Published: December 2015

AimTo explain the subadditive efficacy typically observed with initial combination treatments for type 2 diabetes.MethodsIndividual subject data from 1186 patients with type 2 diabetes [mean glycated haemoglobin (HbA1c) = 8.8%] treated with metformin, canagliflozin or canagliflozin + metformin were used. The baseline HbA1c versus ΔHbA1c relationships for monotherapy arms were determined using analysis of covariance and then used to predict efficacy in the combination arms by modelling how applying one treatment lowers the ‘effective baseline HbA1c’ for a second treatment. The model was further tested using data from several published combination studies.ResultsThe mean ΔHbA1c levels were −1.25, −1.33, −1.37, −1.77 and −1.81% with metformin, canagliflozin 100 mg, canagliflozin 300 mg, canagliflozin 100 mg/metformin and canagliflozin 300 mg/metformin, respectively. Using the monotherapy results, the predicted efficacy for the canagliflozin/metformin arms was within 10% of the observed values using the new model, whereas assuming simple additivity overpredicted efficacy in the combination arms by nearly 50%. For 10 other published initial combination studies, predictions from the new model [mean (standard error) predicted ΔHbA1c = 1.67% (0.14)] were much more consistent with observed values [ΔHbA1c = 1.72% (0.12)] than predictions based on assuming additivity [predicted ΔHbA1c = 2.19% (0.21)].ConclusionsThe less‐than‐additive efficacy commonly seen with initial combination treatments for type 2 diabetes can be largely explained by the impact of baseline HbA1c on the efficacy of individual treatments. Novel formulas have been developed for predicting the efficacy of combination treatments based on the efficacy of individual treatments and the baseline HbA1c of the target patients.
New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 2)
Authors: Terauchi Y. , Koyama M. , Cheng X. , Takahashi Y. , Riddle M. C. , Bolli G. B. , Hirose T. 
Published: December 2015

AimsTo compare the efficacy and safety of insulin glargine 300 U/ml (Gla‐300) with glargine 100 U/ml (Gla‐100) in Japanese people with type 2 diabetes using basal insulin plus oral antihyperglycaemic drug(s) [OAD(s)].MethodsThe EDITION JP 2 study (NCT01689142) was a 6‐month, multicentre, open‐label, phase III study. Participants (n = 241, male 61%, mean diabetes duration 14 years, mean weight 67 kg, mean body mass index 25 kg/m2, mean glycated haemoglobin (HbA1c) 8.02 %, mean basal insulin dose 0.24 U/kg/day) were randomized to Gla‐300 or Gla‐100, while continuing OAD(s). Basal insulin was titrated to target fasting self‐monitored plasma glucose 4.4−5.6 mmol/l. The primary efficacy endpoint was HbA1c change over 6 months. Safety endpoints included hypoglycaemia and weight change.ResultsGla‐300 was non‐inferior to Gla‐100 for HbA1c reduction [least squares (LS) mean difference 0.10 (95% confidence interval [CI] −0.08, 0.27) %]. The mean HbA1c at month 6 was 7.56 and 7.52 % with Gla‐300 and Gla‐100, respectively. Nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia risk was 38% lower with Gla‐300 versus Gla‐100 [relative risk 0.62 (95% CI 0.44, 0.88)]; annualized rates were 55% lower at night [rate ratio 0.45 (95% CI 0.21, 0.96)] and 36% lower at any time [24 h; rate ratio 0.64 (95% CI 0.43, 0.96)]. Severe hypoglycaemia was infrequent. A significant between‐treatment difference in weight change favoured Gla‐300 [LS mean difference −1.0 (95% CI −1.5, −0.5) kg; p = 0.0003]. Adverse event rates were comparable between groups.ConclusionsJapanese people with type 2 diabetes using basal insulin plus OAD(s) experienced less hypoglycaemia with Gla‐300 than with Gla‐100, while glycaemic control did not differ.
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

AbstractNatural 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

AbstractCurrent 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

SummaryObjectiveTwo 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.MethodsThe 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.ResultsAt 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).SignificanceIn 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

AbstractWoody 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

ObjectivesThe 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.MethodsA 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.ResultsIndividuals 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.ConclusionsIn 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

AbstractThe 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

AbstractThe 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

AbstractIreland 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

AbstractWe 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

AbstractSpain'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

AbstractIn 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

AbstractGiven 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.