Application of a new method for GWAS in a related case/control sample with known pedigree structure: identification of new loci for nephrolithiasis

In contrast to large GWA studies based on thousands of individuals and large meta-analyses combining GWAS results, we analyzed a small case/control sample for uric acid nephrolithiasis. Our cohort of closely related individuals is derived from a small, genetically isolated village in Sardinia, with well-characterized genealogical data linking the extant population up to the 16(th) century. It is expected that the number of risk alleles involved in complex disorders is smaller in isolated founder populations than in more diverse populations, and the power to detect association with complex traits may be increased when related, homogeneous affected individuals are selected, as they are more likely to be enriched with and share specific risk variants than are unrelated, affected individuals from the general population. When related individuals are included in an association study, correlations among relatives must be accurately taken into account to ensure validity of the results. A recently proposed association method uses an empirical genotypic covariance matrix estimated from genome-screen data to allow for additional population structure and cryptic relatedness that may not be captured by the genealogical data. We apply the method to our data, and we also investigate the properties of the method, as well as other association methods, in our highly inbred population, as previous applications were to outbred samples. The more promising regions identified in our initial study in the genetic isolate were then further investigated in an independent sample collected from the Italian population. Among the loci that showed association in this study, we observed evidence of a possible involvement of the region encompassing the gene LRRC16A, already associated to serum uric acid levels in a large meta-analysis of 14 GWAS, suggesting that this locus might lead a pathway for uric acid metabolism that may be involved in gout as well as in nephrolithiasis

N-isobutyl-1,8-bis(isobutylamino)-naphthalimide

Naphthalimides make up a class of organic molecules characterised by excellent spectroscopic properties due to their extended conjugate system. Furthermore, various asymmetric or symmetric compounds can be obtained from naphthalimides by the different functionalization that can be performed on the nitrogen and/or on the aromatic rings. The introduction of a wide range of substituents in different positions allows chemical and spectroscopic properties to be regulated. In this contribution, we report the synthesis and characterization of a new 4,5-amino-1,8-naphthalimide bearing three isobutyl substituents

Using the Oxford Cognitive Screen to Detect Cognitive Impairment in Stroke Patients: A Comparison with the Mini-Mental State Examination

BackgroundThe Oxford Cognitive Screen (OCS) was recently developed with the aim of describing the cognitive deficits after stroke. The scale consists of 10 tasks encompassing five cognitive domains: attention and executive function, language, memory, number processing, and praxis. OCS was devised to be inclusive and un-confounded by aphasia and neglect. As such, it may have a greater potential to be informative on stroke cognitive deficits of widely used instruments, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment, which were originally devised for demented patients.ObjectiveThe present study compared the OCS with the MMSE with regards to their ability to detect cognitive impairments post-stroke. We further aimed to examine performance on the OCS as a function of subtypes of cerebral infarction and clinical severity.Methods325 first stroke patients were consecutively enrolled in the study over a 9-month period. The OCS and MMSE, as well as the Bamford classification and NIHSS, were given according to standard procedures.ResultsAbout a third of patients (35.3%) had a performance lower than the cutoff (<22) on the MMSE, whereas 91.6% were impaired in at least one OCS domain, indicating higher incidences of impairment for the OCS. More than 80% of patients showed an impairment in two or more cognitive domains of the OCS. Using the MMSE as a standard of clinical practice, the comparative sensitivity of OCS was 100%. Out of the 208 patients with normal MMSE performance 180 showed impaired performance in at least one domain of the OCS. The discrepancy between OCS and MMSE was particularly strong for patients with milder strokes. As for subtypes of cerebral infarction, fewer patients demonstrated widespread impairments in the OCS in the Posterior Circulation Infarcts category than in the other categories.ConclusionOverall, the results showed a much higher incidence of cognitive impairment with the OCS than with the MMSE and demonstrated no false negatives for OCS vs MMSE. It is concluded that OCS is a sensitive screen tool for cognitive deficits after stroke. In particular, the OCS detects high incidences of stroke-specific cognitive impairments, not detected by the MMSE, demonstrating the importance of cognitive profiling

Annotated corpora and tools of the PARSEME Shared Task on Automatic Identification of Verbal Multiword Expressions (edition 1.1)

This multilingual resource contains corpora in which verbal MWEs have been manually annotated. VMWEs include idioms (let the cat out of the bag), light-verb constructions (make a decision), verb-particle constructions (give up), inherently reflexive verbs (help oneself), and multi-verb constructions (make do). VMWEs were annotated according to the universal guidelines in 19 languages. The corpora are provided in the cupt format, inspired by the CONLL-U format. The corpora were used in the 1.1 edition of the PARSEME Shared Task (2018). For most languages, morphological and syntactic information ­­­­– not necessarily using UD tagsets – including parts of speech, lemmas, morphological features and/or syntactic dependencies are also provided. Depending on the language, the information comes from treebanks (e.g., Universal Dependencies) or from automatic parsers trained on treebanks (e.g., UDPipe). This item contains training, development and test data, as well as the evaluation tools used in the PARSEME Shared Task 1.1 (2018). The annotation guidelines are available online: http://parsemefr.lif.univ-mrs.fr/parseme-st-guidelines/1.

Annotated corpora and tools of the PARSEME Shared Task on Automatic Identification of Verbal Multiword Expressions (edition 1.1)

This multilingual resource contains corpora in which verbal MWEs have been manually annotated. VMWEs include idioms (let the cat out of the bag), light-verb constructions (make a decision), verb-particle constructions (give up), inherently reflexive verbs (help oneself), and multi-verb constructions (make do). VMWEs were annotated according to the universal guidelines in 19 languages. The corpora are provided in the cupt format, inspired by the CONLL-U format. The corpora were used in the 1.1 edition of the PARSEME Shared Task (2018). For most languages, morphological and syntactic information ­­­­– not necessarily using UD tagsets – including parts of speech, lemmas, morphological features and/or syntactic dependencies are also provided. Depending on the language, the information comes from treebanks (e.g., Universal Dependencies) or from automatic parsers trained on treebanks (e.g., UDPipe). This item contains training, development and test data, as well as the evaluation tools used in the PARSEME Shared Task 1.1 (2018). The annotation guidelines are available online: http://parsemefr.lif.univ-mrs.fr/parseme-st-guidelines/1.