A new species of Brachycephalus (Anura Brachycephalidae) from Santa Catarina, southern Brazil

A new species of Brachycephalus (Anura: Brachycephalidae) is described from the Atlantic Forest of northeastern state of Santa Catarina, southern Brazil. Nine specimens (eight adults and a juvenile) were collected from the leaf litter of montane forests 790–835 m above sea level (a.s.l.). The new species is a member of the pernix group by its bufoniform shape and the absence of dermal co-ossification and is distinguished from all its congeners by a combination of its general coloration (dorsal region of head, dorsum, legs, arms, and flanks light, brownish green to dark, olive green, with darker region in the middle of the dorsum and a white line along the vertebral column in most specimens) and by its smooth dorsum. The geographical distribution of the new species is highly reduced (extent of occurrence estimated as 25.04 ha, or possibly 34.37 ha). In addition, its habitat has experienced some level of degradation, raising concerns about the future conservation of the species. Preliminary density estimates suggest one calling individual every 3–4 m2 at 815–835 m a.s.l. and every 100 m2 at 790 m a.s.l. Together with the recently described B. boticario and B. fuscolineatus, the new species is among the southernmost species of Brachycephalus known to date

Excitation lines and the breakdown of Stokes-Einstein relations in supercooled liquids

By applying the concept of dynamical facilitation and analyzing the excitation lines that result from this facilitation, we investigate the origin of decoupling of transport coefficients in supercooled liquids. We illustrate our approach with two classes of models. One depicts diffusion in a strong glass former, and the other in a fragile glass former. At low temperatures, both models exhibit violation of the Stokes-Einstein relation, $D\sim\tau^{-1}$, where $D$ is the self diffusion constant and $\tau$ is the structural relaxation time. In the strong case, the violation is sensitive to dimensionality $d$, going as $D\sim\tau^{-2/3}$ for $d=1$, and as $D\sim \tau^{-0.95}$ for $d=3$. In the fragile case, however, we argue that dimensionality dependence is weak, and show that for $d=1$, $D \sim \tau^{-0.73}$. This scaling for the fragile case compares favorably with the results of a recent experimental study for a three-dimensional fragile glass former.Comment: 7 pages, 7 figures, submitted to Phys. Rev.

Agreement between administrative data and the Resident Assessment Instrument Minimum Dataset (RAI-MDS) for medication use in long-term care facilities: a population-based study

Background: Prescription medication use, which is common among long-term care facility (LTCF) residents, is routinely used to describe quality of care and predict health outcomes. Data sources that capture medication information, which include surveys, medical charts, administrative health databases, and clinical assessment records, may not collect concordant information, which can result in comparable prevalence and effect size estimates. The purpose of this research was to estimate agreement between two population-based electronic data sources for measuring use of several medication classes among LTCF residents: outpatient prescription drug administrative data and the Resident Assessment Instrument Minimum Data Set (RAI-MDS) Version 2.0. Methods: Prescription drug and RAI-MDS data from the province of Saskatchewan, Canada (population 1.1 million) were linked for 2010/11 in this cross-sectional study. Agreement for anti-psychotic, anti-depressant, and anti-anxiety/hypnotic medication classes was examined using prevalence estimates, Cohen’s κ, and positive and negative agreement. Mixed-effects logistic regression models tested resident and facility characteristics associated with disagreement. Results: The cohort was comprised of 8,866 LTCF residents. In the RAI-MDS data, prevalence of anti-psychotics was 35.7%, while for anti-depressants it was 37.9% and for hypnotics it was 27.1%. Prevalence was similar in prescription drug data for anti-psychotics and anti-depressants, but lower for hypnotics (18.0%). Cohen’s κ ranged from 0.39 to 0.85 and was highest for the first two medication classes. Diagnosis of a mood disorder and facility affiliation was associated with disagreement for hypnotics. Conclusions: Agreement between prescription drug administrative data and RAI-MDS assessment data was influenced by the type of medication class, as well as selected patient and facility characteristics. Researchers should carefully consider the purpose of their study, whether it is to capture medication that are dispensed or medications that are currently used by residents, when selecting a data source for research on LTCF populations

Phylogeography and Ethnogenesis of Aboriginal Southeast Asians

Studying the genetic history of the Orang Asli of Peninsular Malaysia can provide crucial clues to the peopling of Southeast Asia as a whole. We have analyzed mitochondrial DNA (mtDNAs) control-region and coding-region markers in 447 mtDNAs from the region, including 260 Orang Asli, representative of each of the traditional groupings, the Semang, the Senoi, and the Aboriginal Malays, allowing us to test hypotheses about their origins. All of the Orang Asli groups have undergone high levels of genetic drift, but phylogeographic traces nevertheless remain of the ancestry of their maternal lineages. The Semang have a deep ancestry within the Malay Peninsula, dating to the initial settlement from Africa >50,000 years ago. The Senoi appear to be a composite group, with approximately half of the maternal lineages tracing back to the ancestors of the Semang and about half to Indochina. This is in agreement with the suggestion that they represent the descendants of early Austroasiatic speaking agriculturalists, who brought both their language and their technology to the southern part of the peninsula ∼4,000 years ago and coalesced with the indigenous population. The Aboriginal Malays are more diverse, and although they show some connections with island Southeast Asia, as expected, they also harbor haplogroups that are either novel or rare elsewhere. Contrary to expectations, complete mtDNA genome sequences from one of these, R9b, suggest an ancestry in Indochina around the time of the Last Glacial Maximum, followed by an early-Holocene dispersal through the Malay Peninsula into island Southeast Asia

Model-Based Security Testing

Security testing aims at validating software system requirements related to security properties like confidentiality, integrity, authentication, authorization, availability, and non-repudiation. Although security testing techniques are available for many years, there has been little approaches that allow for specification of test cases at a higher level of abstraction, for enabling guidance on test identification and specification as well as for automated test generation. Model-based security testing (MBST) is a relatively new field and especially dedicated to the systematic and efficient specification and documentation of security test objectives, security test cases and test suites, as well as to their automated or semi-automated generation. In particular, the combination of security modelling and test generation approaches is still a challenge in research and of high interest for industrial applications. MBST includes e.g. security functional testing, model-based fuzzing, risk- and threat-oriented testing, and the usage of security test patterns. This paper provides a survey on MBST techniques and the related models as well as samples of new methods and tools that are under development in the European ITEA2-project DIAMONDS.Comment: In Proceedings MBT 2012, arXiv:1202.582

Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and is a future component of donor scoring criteria

CDKN2A is a proven and validated biomarker of ageing which acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest pre-transplant predictor of post- transplant serum creatinine when compared to “Gold Standard” clinical factors, such as cold ischaemic time and donor chronological age. This report shows that CDKN2A is better than telomere length, the most celebrated biomarker of ageing, as a predictor of post-transplant renal function. It also shows that CDKN2A is as strong a determinant of post-transplant organ function when compared to extended criteria (ECD) kidneys. A multivariate analysis model was able to predict up to 27.1% of eGFR at one year post-transplant (p = 0.008). Significantly, CDKN2A was also able to strongly predict delayed graft function. A pre-transplant donor risk classification system based on CDKN2A and ECD criteria is shown to be feasible and commendable for implementation in the near future

Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance

Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder. In total, 11,878 non-synonymous variants from 6,396 genes were tested for their association with schizophrenia spectrum disorders. Pathway enrichment analyses were conducted on gene-based test results, protein-protein interaction (PPI) networks, and epistatic effects. Using a significance threshold of FDR\u3c0.1, association was detected for rs10941112 (P=2.1×10−5; q-value=0.073) in AMACR, a gene involved in fatty acid metabolism and previously implicated in schizophrenia, with significant cis effects on gene expression (P=5.5×10−4), including brain tissue data from the Genotype-Tissue Expression project (minimum P=6.0×10−5). A second SNP, rs10378 located in TMEM176A, also shows risk effects in the exome data (P=2.8×10−5; q-value=0.073). Protein-protein interactions among our top gene-based association results (P\u3c0.05; n=359 genes) reveal significant enrichment of genes involved in NCAM-mediated neurite outgrowth (P=3.0×10−5), while exome-wide SNP-SNP interaction effects for rs10941112 and rs10378 indicate a potential role for kinase-mediated signaling involved in memory and learning. In conclusion, these association results implicate AMACR and TMEM176A in schizophrenia risk, whose effects may be modulated by genes involved in synaptic plasticity and neurocognitive performance

Diaryl- and triaryl-pyrrole derivatives:Inhibitors of the MDM2-p53 and MDMX-p53 protein-protein interactions

Screening identified 2-(3-((4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl)-2,5-dimethyl-1H-pyrrol-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile as an MDM2–p53 inhibitor (IC(50) = 12.3 μM). MDM2–p53 and MDMX–p53 activity was seen for 5-((1-(4-chlorophenyl)-2,5-diphenyl-1H-pyrrol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (MDM2 IC(50) = 0.11 μM; MDMX IC(50) = 4.2 μM) and 5-((1-(4-nitrophenyl)-2,5-diphenyl-1H-pyrrol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (MDM2 IC(50) = 0.15 μM; MDMX IC(50) = 4.2 μM), and cellular activity consistent with p53 activation in MDM2 amplified cells. Further SAR studies demonstrated the requirement for the triarylpyrrole moiety for MDMX–p53 activity but not for MDM2–p53 inhibition