LRP-1 variation is not associated with risk of Alzheimer's disease

Alzheimer's disease (AD) is characterised by the extensive deposition of amyloid beta (Aß) within the parenchyma and vasculature of the brain. It is hypothesised that a dysfunction in Aß degradation and/or its removal from the brain may result in accumulation as plaques. Low density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional receptor shown to be involved in cholesterol metabolism but also the removal of Aß from the brain. Its ability to transport Aß from the brain to the periphery has made it an attractive candidate for involvement in Alzheimer's disease (AD). We have assessed the frequencies of 9 tag- SNPs and the commonly studied synonymous SNP within exon 3 (rs1799986) in a multi-centre AD/control cohort and performed haplotype analysis. We found no evidence from a combined total of 412 controls and 1057 AD patients to support the involvement of LRP-1 variation, including the most commonly studied variant in rs1799986 in conferring genetic susceptibility to increased risk of AD.

Measuring oxygen reduction/evolution reactions on the nanoscale

The efficiency of fuel cells and metal-air batteries is significantly limited by the activation of oxygen reduction and evolution reactions. Despite the well-recognized role of oxygen reaction kinetics on the viability of energy technologies, the governing mechanisms remain elusive and until now have been addressable only by macroscopic studies. This lack of nanoscale understanding precludes optimization of material architecture. Here, we report direct measurements of oxygen reduction/evolution reactions and oxygen vacancy diffusion on oxygen-ion conductive solid surfaces with sub-10 nm resolution. In electrochemical strain microscopy, the biased scanning probe microscopy tip acts as a moving, electrocatalytically active probe exploring local electrochemical activity. The probe concentrates an electric field in a nanometre-scale volume of material, and bias-induced, picometre-level surface displacements provide information on local electrochemical processes. Systematic mapping of oxygen activity on bare and platinum-functionalized yttria-stabilized zirconia surfaces is demonstrated. This approach allows direct visualization of the oxygen reduction/evolution reaction activation process at the triple-phase boundary, and can be extended to a broad spectrum of oxygen-conductive and electrocatalytic materials.

Comparison of Wavelet Transform and Time-Domain Analysis of Second Trimester Uterine Artery Doppler Waveforms in Screening for Pre-Eclampsia

The aim of this study was to compare time-domain waveform analysis of second-trimester uterine artery Doppler using the resistance index (RI) with waveform analysis using a mathematical tool known as wavelet transform for the prediction of pre-eclampsia (PE). This was a retrospective, nested case-cohort study of 336 women, 37 of whom subsequently developed PE. Uterine artery Doppler waveforms were analysed using both RI and waveform analysis. The utility of these indices in screening for PE was then evaluated using receiver operating characteristic curves. There were significant differences in uterine artery RI between the PE women and those with normal pregnancy outcome. After wavelet analysis, significant difference in the mean amplitude in wavelet frequency band 4 was noted between the 2 groups. The sensitivity for both Doppler RI and frequency band 4 for the detection of PE at a 10% false-positive rate was 45%. This small study demonstrates the application of wavelet transform analysis of uterine artery Doppler waveforms in screening for PE. Further prospective studies are needed in order to clearly define if this analytical approach to waveform analysis may have the potential to improve the detection of PE by uterine artery Doppler screening.

Large-scale spatial patterns in the distribution of Collembola (Hexapoda) species in Antarctic terrestrial ecosystems

We tested whether the distribution of three common springtail species (Gressittacantha terranova, Gomphiocephalus hodgsoni and Friesea grisea) in Victoria Land (Antarctica) could be modelled as a function of latitude, longitude, altitude and distance from the sea.

Victoria Land, Ross Dependency, Antarctica.

Generalized linear models were constructed using species presence/absence data relative to geographical features (latitude, longitude, altitude, distance from sea) across the species' entire ranges. Model results were then integrated with the known phylogeography of each species and hypotheses were generated on the role of climate as a major driver of Antarctic springtail distribution.

Based on model selection using Akaike's information criterion, the species' distributions were: hump-shaped relative to longitude and monotonic with altitude for Gressittacantha terranova; hump-shaped relative to latitude and monotonic with altitude for Gomphiocephalus hodgsoni; and hump-shaped relative to longitude and monotonic with latitude, altitude and distance from the sea for Friesea grisea.

No single distributional pattern was shared by the three species. While distributions were partially a response to climatic spatial clines, the patterns observed strongly suggest that past geological events have influenced the observed distributions. Accordingly, present-day spatial patterns are likely to have arisen from the interaction of historical and environmental drivers. Future studies will need to integrate a range of spatial and temporal scales to further quantify their respective roles.

Tuning non-Markovianity by spin-dynamics control

We study the interplay between forgetful and memory-keeping evolution enforced on a two-level system by a multi-spin environment whose elements are coupled to local bosonic baths. Contrarily to the expectation that any non-Markovian effect would be buried by the forgetful mechanism induced by the spin-bath coupling, one can actually induce a full Markovian-to-non-Markovian transition of the two-level system's dynamics, controllable by parameters such as the mismatch between the energy of the two-level system and of the spin environment. For a symmetric coupling, the amount of non-Markovianity surprisingly grows with the number of decoherence channels. DOI: 10.1103/PhysRevA.87.022317

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Revised response criteria for polycythemia vera and essential thrombocythemia:an ELN and IWG-MRT consensus project

Standardized response criteria to interpret and compare clinical trials are needed for approval of new therapeutic agents by regulatory agencies. The European LeukemiaNet (ELN) response criteria for essential thrombocythemia (ET) and polycythemia vera (PV) issued in 2009 have been widely adopted as end points in a number of recent clinical trials. However, evidence exists that they do not predict response or provide clinically relevant measures of benefit for the patients. This article presents revised recommendations for assessing response in ET and PV provided by a working group established by ELN and International Working Group-Myeloproliferative Neoplasms Research and Treatment. New definitions of complete and partial remission incorporate clinical, hematological, and histological response assessments that include a standardized symptom assessment form and consider absence of disease progression and vascular events. We anticipate that these criteria will be adopted widely to facilitate the development of new and more effective therapies for ET and PV.

Probing Bias-Dependent Electrochemical Gas-Solid Reactions in (LaxSr1-x)CoO3-delta Cathode Materials

Spatial variability of bias-dependent electrochemical processes on a (La0.5Sr0.5)(2)CoO4 +/- modified (LaxSr1-x)CoO3- surface is studied using first-order reversal curve method in electrochemical strain microscopy (ESM). The oxygen reduction/evolution reaction (ORR/OER) is activated at voltages as low as 3-4 V with respect to bottom electrode. The degree of bias-induced transformation as quantified by ESM hysteresis loop area increases with applied bias. The variability of electrochemical activity is explored using correlation analysis and the ORR/OER is shown to be activated in grains at relatively low biases, but the final reaction rate is relatively small. At the same time, at grain boundaries, the onset of reaction process corresponds to larger voltages, but limiting reactivity is much higher. The reaction mechanism in ESM of mixed electronic-ionic conductor is further analyzed. These studies both establish the framework for probing bias-dependent electrochemical processes in solids and demonstrate rich spectrum of electrochemical transformations underpinning catalytic activity in cobaltites.

Il Piano della Performance 2011-2013 dei Comuni italiani di medie e grandi dimensioni: allineamento normativo e adeguatezza programmatica in ottica economico-aziendale

Il presente lavoro intende individuare le possibili configurazioni di Piano della Performance (PdP) utilizzabili dagli enti locali, provvedendo poi a delineare il livello di distribuzione e di allineamento dei PdP 2011-2013 dei Comuni medi e grandi rispetto alle suddette configurazioni. Inoltre, verrà valutato, tramite una griglia predisposta dagli autori, il livello di adeguatezza programmatica dei Piani della Performance dei Comuni medi e grandi, al fine di confermare le configurazioni esistenti o di proporne una nuova in caso di inadeguatezza delle prime.

La contabilità come mezzo per diffondere i valori religiosi. Il caso della diocesi di Ferrara del XV secolo.

Il tema del ruolo della contabilità nella Chiesa, con particolare riferimento al legame esistente tra contabilità e valori religiosi, non appare ad oggi sufficientemente studiato, soprattutto se si considera l’importanza economica e sociale di tale istituzione nel passato e nel presente. Il lavoro intende contribuire a tale indagine analizzando la realtà della Diocesi di Ferrara del XV secolo. Il Quattrocento rappresenta per la Chiesa italiana un’epoca di grande importanza, in quanto caratterizzato da un tentativo di riforma promosso da Papa Eugenio IV, volto a combattere la dilagante corruzione morale all’interno del clero e a riportare quest’ultimo alla sua funzione pastorale. L’appello pontificio venne accolto con particolare attenzione da due vescovi ferraresi, Giovanni Tavelli da Tossignano e Francesco Dal Legname, che attraverso le loro visite pastorali cercarono di divulgare i valori della riforma nella propria Diocesi. La promozione della nuova moralità, nell’esperienza ferrarese, era basata anche sulla diffusione degli strumenti contabili, mezzo essenziale per mettere in luce l’operato dei diversi membri del clero ed in particolare l’utilizzo da parte loro dei beni della Chiesa. Attraverso lo studio di documenti originali del XV secolo, scritti in lingua latina, il contributo si propone di mettere in luce come la contabilità possa assumere un ruolo complementare alla promozione dei valori religiosi.

Relatively Absolute? The Undermining of Article 3 ECHR in Ahmad v UK

The recent decision of the European Court of Human Rights in Ahmad v UK dangerously undermines the well-established case law of the Court on counter-terrorism and non-refoulement towards torture, inhuman and degrading treatment or punishment. Although ostensibly rejecting the ‘relativist’ approach to Article 3 ECHR adopted by the House of Lords in Wellington v Secretary of State for the Home Department, the Court appeared to accept that what is a breach of Article 3 in a domestic context may not be a breach in an extradition or expulsion context. This statement is difficult to reconcile with the jurisprudence constante of the Court in the last fifteen years, according to which Article 3 ECHR is an absolute right in all its applications, including non-refoulement, regardless of who the potential victim of torture, inhuman or degrading treatment is, what she may have done, or where the treatment at issue would occur.

Geometrical characterization of non-Markovianity

We introduce a tool for the quantitative characterization of the departure from Markovianity of a given dynamical process. Our tool can be applied to a generic N-level system and extended straightforwardly to Gaussian continuous-variable systems. It is linked to the change of the volume of physical states that are dynamically accessible to a system and provides qualitative expectations in agreement with some of the analogous tools proposed so far. We illustrate its predictive power by tackling a few canonical examples.

Novel genetic susceptibility loci for diabetic end-stage renal disease identified through robust naive Bayes classification

Aims/hypothesis: Diabetic nephropathy is a major diabetic complication, and diabetes is the leading cause of end-stage renal disease (ESRD). Family studies suggest a hereditary component for diabetic nephropathy. However, only a few genes have been associated with diabetic nephropathy or ESRD in diabetic patients. Our aim was to detect novel genetic variants associated with diabetic nephropathy and ESRD. Methods: We exploited a novel algorithm, ‘Bag of Naive Bayes’, whose marker selection strategy is complementary to that of conventional genome-wide association models based on univariate association tests. The analysis was performed on a genome-wide association study of 3,464 patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study and subsequently replicated with 4,263 type 1 diabetes patients from the Steno Diabetes Centre, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK collection (UK–Republic of Ireland) and the Genetics of Kidneys in Diabetes US Study (GoKinD US). Results: Five genetic loci (WNT4/ZBTB40-rs12137135, RGMA/MCTP2-rs17709344, MAPRE1P2-rs1670754, SEMA6D/SLC24A5-rs12917114 and SIK1-rs2838302) were associated with ESRD in the FinnDiane study. An association between ESRD and rs17709344, tagging the previously identified rs12437854 and located between the RGMA and MCTP2 genes, was replicated in independent case–control cohorts. rs12917114 near SEMA6D was associated with ESRD in the replication cohorts under the genotypic model (p < 0.05), and rs12137135 upstream of WNT4 was associated with ESRD in Steno. Conclusions/interpretation: This study supports the previously identified findings on the RGMA/MCTP2 region and suggests novel susceptibility loci for ESRD. This highlights the importance of applying complementary statistical methods to detect novel genetic variants in diabetic nephropathy and, in general, in complex diseases.