Bis(tetra­phenyl­arsonium) di-μ-hy­droxido-bis­[(nitrilo­triacetato)­cobalt(III)] octa­hydrate

In the title compound, (C24H20As)2[Co2(C6H6NO6)2(OH)2]·8H2O, the CoIII atom in the binuclear centrosymmetric anion is octa­hedrally surrounded by one N atom and three O atoms of the tetra­dentate nitrilo­triacetate ligand and two μ-hydroxide ligands. The crystal packing is controlled by C—H⋯O and O—H⋯O hydrogen-bonding inter­actions. The crystal employed in this study proved to be a two-component twin around (01)

Mapping of the S. demissum late blight resistance gene R8 to a new locus on chromosome IX

The use of resistant varieties is an important tool in the management of late blight, which threatens potato production worldwide. Clone MaR8 from the Mastenbroek differential set has strong resistance to Phytophthora infestans, the causal agent of late blight. The F1 progeny of a cross between the susceptible cultivar Concurrent and MaR8 were assessed for late blight resistance in field trials inoculated with an incompatible P. infestans isolate. A 1:1 segregation of resistance and susceptibility was observed, indicating that the resistance gene referred to as R8, is present in simplex in the tetraploid MaR8 clone. NBS profiling and successive marker sequence comparison to the potato and tomato genome draft sequences, suggested that the R8 gene is located on the long arm of chromosome IX and not on the short arm of chromosome XI as was suggested previously. Analysis of SSR, CAPS and SCAR markers confirmed that R8 was on the distal end of the long arm of chromosome IX. R gene cluster directed profiling markers CDPSw54 and CDPSw55 flanked the R8 gene at the distal end (1 cM). CDPTm21-1, CDPTm21-2 and CDPTm22 flanked the R8 gene on the proximal side (2 cM). An additional co-segregating marker (CDPHero3) was found, which will be useful for marker assisted breeding and map based cloning of R8

Distribution of P1(D1) wart disease resistance in potato germplasm and GWAS identification of haplotype-specific SNP markers

Key message: A Genome-Wide Association Study using 330 commercial potato varieties identified haplotype specific SNPmarkers associated with pathotype 1(D1) wart disease resistance. Abstract: Synchytrium endobioticum is a soilborne obligate biotrophic fungus responsible for wart disease. Growing resistant varieties is the most effective way to manage the disease. This paper addresses the challenge to apply molecular markers in potato breeding. Although markers linked to Sen1 were published before, the identification of haplotype-specific single-nucleotide polymorphisms may result in marker assays with high diagnostic value. To identify hs-SNP markers, we performed a genome-wide association study (GWAS) in a panel of 330 potato varieties representative of the commercial potato gene pool. SNP markers significantly associated with pathotype 1 resistance were identified on chromosome 11, at the position of the previously identified Sen1 locus. Haplotype specificity of the SNP markers was examined through the analysis of false positives and false negatives and validated in two independent full-sib populations. This paper illustrates why it is not always feasible to design markers without false positives and false negatives for marker-assisted selection. In the case of Sen1, founders could not be traced because of a lack of identity by descent and because of the decay of linkage disequilibrium between Sen1 and flanking SNP markers. Sen1 appeared to be the main source of pathotype 1 resistance in potato varieties, but it does not explain all the resistance observed. Recombination and introgression breeding may have introduced new, albeit rare haplotypes involved in pathotype 1 resistance. The GWAS approach, in such case, is instrumental to identify SNPs with the best possible diagnostic value for marker-assisted breeding.</p

Atrophy in the parahippocampal gyrus as an early biomarker of Alzheimer’s disease

The main aim of the present study was to compare volume differences in the hippocampus and parahippocampal gyrus as biomarkers of Alzheimer’s disease (AD). Based on the previous findings, we hypothesized that there would be significant volume differences between cases of healthy aging, amnestic mild cognitive impairment (aMCI), and mild AD. Furthermore, we hypothesized that there would be larger volume differences in the parahippocampal gyrus than in the hippocampus. In addition, we investigated differences between the anterior, middle, and posterior parts of both structures. We studied three groups of participants: 18 healthy participants without memory decline, 18 patients with aMCI, and 18 patients with mild AD. 3 T T1-weighted MRI scans were acquired and gray matter volumes of the anterior, middle, and posterior parts of both the hippocampus and parahippocampal gyrus were measured using a manual tracing approach. Volumes of both the hippocampus and parahippocampal gyrus were significantly different between the groups in the following order: healthy > aMCI > AD. Volume differences between the groups were relatively larger in the parahippocampal gyrus than in the hippocampus, in particular, when we compared healthy with aMCI. No substantial differences were found between the anterior, middle, and posterior parts of both structures. Our results suggest that parahippocampal volume discriminates better than hippocampal volume between cases of healthy aging, aMCI, and mild AD, in particular, in the early phase of the disease. The present results stress the importance of parahippocampal atrophy as an early biomarker of AD

Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer’s disease

Biomarkers of brain Aβ amyloid deposition can be measured either by cerebrospinal fluid Aβ42 or Pittsburgh compound B positron emission tomography imaging. Our objective was to evaluate the ability of Aβ load and neurodegenerative atrophy on magnetic resonance imaging to predict shorter time-to-progression from mild cognitive impairment to Alzheimer’s dementia and to characterize the effect of these biomarkers on the risk of progression as they become increasingly abnormal. A total of 218 subjects with mild cognitive impairment were identified from the Alzheimer’s Disease Neuroimaging Initiative. The primary outcome was time-to-progression to Alzheimer’s dementia. Hippocampal volumes were measured and adjusted for intracranial volume. We used a new method of pooling cerebrospinal fluid Aβ42 and Pittsburgh compound B positron emission tomography measures to produce equivalent measures of brain Aβ load from either source and analysed the results using multiple imputation methods. We performed our analyses in two phases. First, we grouped our subjects into those who were ‘amyloid positive’ (n = 165, with the assumption that Alzheimer's pathology is dominant in this group) and those who were ‘amyloid negative’ (n = 53). In the second phase, we included all 218 subjects with mild cognitive impairment to evaluate the biomarkers in a sample that we assumed to contain a full spectrum of expected pathologies. In a Kaplan–Meier analysis, amyloid positive subjects with mild cognitive impairment were much more likely to progress to dementia within 2 years than amyloid negative subjects with mild cognitive impairment (50 versus 19%). Among amyloid positive subjects with mild cognitive impairment only, hippocampal atrophy predicted shorter time-to-progression (P < 0.001) while Aβ load did not (P = 0.44). In contrast, when all 218 subjects with mild cognitive impairment were combined (amyloid positive and negative), hippocampal atrophy and Aβ load predicted shorter time-to-progression with comparable power (hazard ratio for an inter-quartile difference of 2.6 for both); however, the risk profile was linear throughout the range of hippocampal atrophy values but reached a ceiling at higher values of brain Aβ load. Our results are consistent with a model of Alzheimer’s disease in which Aβ deposition initiates the pathological cascade but is not the direct cause of cognitive impairment as evidenced by the fact that Aβ load severity is decoupled from risk of progression at high levels. In contrast, hippocampal atrophy indicates how far along the neurodegenerative path one is, and hence how close to progressing to dementia. Possible explanations for our finding that many subjects with mild cognitive impairment have intermediate levels of Aβ load include: (i) individual subjects may reach an Aβ load plateau at varying absolute levels; (ii) some subjects may be more biologically susceptible to Aβ than others; and (iii) subjects with mild cognitive impairment with intermediate levels of Aβ may represent individuals with Alzheimer’s disease co-existent with other pathologies

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089

Caracterización de usuario y tráfico en la evolución de la banda ancha en España

El mundo de las telecomunicaciones evoluciona a gran velocidad, acorde con las necesidades de los usuarios. El crecimiento del número de servicios a través de las conexiones que actualmente utilizamos para conectarnos a Internet (Ej. IPTV) con elevados requerimientos de ancho de banda, que junto a los servicios de nuevo nacimiento (ej. OTT), contribuyen tanto al aumento de la necesidad de mayores velocidades de conexión de los usuarios como a la implantación de nuevos modelos de calidad de servicio. Las redes de datos de banda ancha (fija y móvil) actuales deben, por lo tanto, experimentar una profunda transformación para conseguir solventar de una forma eficiente los problemas y las necesidades de tráfico, pudiendo así absorber el progresivo incremento del ancho de banda, dejando las puertas abiertas a futuras mejoras. Y para ello las operadoras se nutrirán con la valiosa información de tráfico y usuario que les lleven a tomar las mejores decisiones de cara a que las transformaciones llevadas a cabo cubran exactamente lo que el usuario demanda de la forma más eficiente posible. Con estas premisas, surgieron las ideas que se plasmaron como objetivos del PFC : La idea de narrar el despliegue de la banda ancha en España desde sus orígenes hasta la actualidad, enfocando su crecimiento desde un punto de vista sociotecnológico. Dando continuidad al punto anterior, se persiguió la idea de conocer las herramientas sociales y tecnológicas a raíz de las cuales se pueda realizar una previsión del tráfico en las redes de las operadoras en un futuro cercano. La pretensión de mostrar las características de los usuarios de banda ancha y del tráfico de datos que generan, que son de carácter crítico para las operadoras en la elaboración de forma adecuada de la planificación de sus redes. La intención de revelar los procedimientos de las operadoras para que, una vez conocidas las características de sus usuarios, se puedan cumplir los requisitos demandados por los mismos: QoS y los indicadores clave de rendimiento (KPIs) Por otro lado, el nivel de detalle dado pretende adecuarse a un público que no tenga profundos conocimientos sobre la materia, y salvo partes bastante concretas, se puede catalogar este trabajo como de abierto al público en general. ABSTRACT. The world of telecommunications is evolving at high speed, according to the needs of users. The growing of services number through the connections that currently have been used to connect to the Internet (eg IPTV ) with high bandwidth requirements, which together with the new birth services (eg OTT ) contribute both to increased the need for higher connection speeds users and the implementation of new models of service quality. Data networks broadband (fixed and mobile ) today must , therefore, undergo a deep transformation to achieve an efficient solving problems and traffic needs, thus being able to absorb the gradual increase of bandwidth, leaving the door open to future improvements. And for that the operators will be nurtured with valuable information and user traffic that lead them to make better decisions in the face of the transformations carried out exactly meet the user demand for the most efficient possible way. With these assumptions, the ideas that emerged were expressed as PFC objectives : The idea of narrating the broadband deployment in Spain from its origins to the present, focusing its growth from a socio-technological approach. Continuing the previous point, it pursued the idea of knowing the social tools and technology as a result of which it can perform a traffic forecast operators networks in the near future. The attempt to show the characteristics of broadband users and data traffic they generate, which are mission critical for operators in developing adequately planning their networks. The intention to disclose procedures for operators, once known the characteristics of their users, it can meet the requirements demanded by them: QoS and key performance indicators (KPI). On the other hand, the level of detail given suit seeks an audience that does not have deep knowledge on the subject, unless quite specific parts, this work can be classified as open to the general public

Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study

Introduction and Aims: The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature. Methods: The DIPAK-1 Study is an ongoing investigator-driven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18–60 years, estimated glomerular filtration rate 30–60 mL/min/1.73 m2) were randomized 1:1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians. Results: We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48–55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m2 [interquartile range: 41–58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p < 0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p < 0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship. Conclusions: These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk–benefit ratio. ClinicalTrials.gov identifier: NCT 01616927

Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease:An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study

Introduction and Aims The DIPAK-1 Study investigates the reno-and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature. Methods The DIPAK-1 Study is an ongoing investigatordriven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18-60 years, estimated glomerular filtration rate 30-60 mL/min/1.73 m(2)) were randomized 1: 1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians. Results We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48-55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m(2) [interquartile range: 41-58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p <0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p <0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship. Conclusions These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk-benefit ratio