Local spatial analysis: an easy-to-use adaptive spatial EEG filter.

Spatial EEG filters are widely used to isolate event-related potential (ERP) components. The most commonly used spatial filters (e.g., the average reference and the surface Laplacian) are "stationary." Stationary filters are conceptually simple, easy to use, and fast to compute, but all assume that the EEG signal does not change across sensors and time. Given that ERPs are intrinsically nonstationary, applying stationary filters can lead to misinterpretations of the measured neural activity. In contrast, "adaptive" spatial filters (e.g., independent component analysis, ICA; and principal component analysis, PCA) infer their weights directly from the spatial properties of the data. They are, thus, not affected by the shortcomings of stationary filters. The issue with adaptive filters is that understanding how they work and how to interpret their output require advanced statistical and physiological knowledge. Here, we describe a novel, easy-to-use, and conceptually simple adaptive filter (local spatial analysis, LSA) for highlighting local components masked by large widespread activity. This approach exploits the statistical information stored in the trial-by-trial variability of stimulus-evoked neural activity to estimate the spatial filter parameters adaptively at each time point. Using both simulated data and real ERPs elicited by stimuli of four different sensory modalities (audition, vision, touch, and pain), we show that this method outperforms widely used stationary filters and allows to identify novel ERP components masked by large widespread activity. Implementation of the LSA filter in MATLAB is freely available to download.NEW & NOTEWORTHY EEG spatial filtering is important for exploring brain function. Two classes of filters are commonly used: stationary and adaptive. Stationary filters are simple to use but wrongly assume that stimulus-evoked EEG responses (ERPs) are stationary. Adaptive filters do not make this assumption but require solid statistical and physiological knowledge. Bridging this gap, we present local spatial analysis (LSA), an adaptive, yet computationally simple, spatial filter based on linear regression that separates local and widespread brain activity (https://www.iannettilab.net/lsa.html or https://github.com/rorybufacchi/LSA-filter).

The GRM7 gene, early response to risperidone, and schizophrenia: a genome-wide association study and a confirmatory pharmacogenetic analysis.

The search for biomarkers of response to antipsychotic medications is hindered by difficulties inherent in the topic or related to persistent methodological difficulties, such as high rates of anticipated discontinuation and consequent distortions in the imputation of missing data. Because early response to antipsychotics represents a sufficiently reliable index of the subsequent treatment response in patients with schizophrenia, we undertook a real-world, genome-wide association study (GWAS) with the aim of identifying genetic predictors of response to risperidone after 2 weeks in 86 patients with schizophrenia. Limited to the associations reaching significance in the GWAS, confirmatory analysis relative to risperidone response over 9 months was also designed involving 97 patients (European only) enroled in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) genetic substudy. The GWAS revealed a significant association (false discovery rate 0.02) of the single-nucleotide polymorphism rs2133450 inside the GRM7 gene with Emsley's positive domain derived from the positive and negative syndrome scale (PANSS). Patients with the rs2133450 CC genotype presented poorer improvement in the positive domain over 2 weeks, with odds ratios of 12.68 (95% CI, 3.51-45.76) and 6.95 (95% confidence interval (CI), 2.37-20.37) compared with patients with the AA and AC genotypes, respectively. Compared with A homozygotes, rs2133450 C homozygotes enroled in the CATIE-derived confirmatory analysis showed less improvement in Emsley's positive, excited and depression domains, positive and general PANSS subtypes, and total PANSS after 9 months of treatment with risperidone. The original GWAS and the CATIE-derived confirmatory analysis support the proposal that the rs2133450 may have translational relevance as a predictor of response to risperidone.

Proteasome system dysregulation and treatment resistance mechanisms in major depressive disorder.

Several studies have demonstrated that allelic variants related to inflammation and the immune system may increase the risk for major depressive disorder (MDD) and reduce patient responsiveness to antidepressant treatment. Proteasomes are fundamental complexes that contribute to the regulation of T-cell function. Only one study has shown a putative role of proteasomal PSMA7, PSMD9 and PSMD13 genes in the susceptibility to an antidepressant response, and sparse data are available regarding the potential alterations in proteasome expression in psychiatric disorders such as MDD. The aim of this study was to clarify the role of these genes in the mechanisms underlying the response/resistance to MDD treatment. We performed a case-control association study on 621 MDD patients, of whom 390 were classified as treatment-resistant depression (TRD), and we collected peripheral blood cells and fibroblasts for mRNA expression analyses. The analyses showed that subjects carrying the homozygous GG genotype of PSMD13 rs3817629 had a twofold greater risk of developing TRD and exhibited a lower PSMD13 mRNA level in fibroblasts than subjects carrying the A allele. In addition, we found a positive association between PSMD9 rs1043307 and the presence of anxiety disorders in comorbidity with MDD, although this result was not significant following correction for multiple comparisons. In conclusion, by confirming the involvement of PSMD13 in the MDD treatment response, our data corroborate the hypothesis that the dysregulation of the complex responsible for the degradation of intracellular proteins and potentially controlling autoimmunity- and immune tolerance-related processes may be involved in several phenotypes, including the TRD.

Ankle-brachial index in a type 2 diabetic population with proliferative retinopathy: associated risk factors and complications.

AIM: The aim of this study was to analyse risk factors and complications associated with low ankle-brachial index (ABI) in a type 2 diabetic population with proliferative retinopathy. METHODS: This study included 181 subjects. ABI was measured with a Doppler device. Subjects with ABI <0.9 were diagnosed with peripheral vascular disease (PVD). The exclusion criterion was medial arterial calcification. RESULTS: The mean (± SD) age and diabetes (DM) duration were 65±9.7 years and 18.6±9.1 years, respectively. ABI <0.9 was associated with increasing age (P<0.001), DM duration (P=0.02), higher total (P=0.02) and LDL cholesterol (P=0.035), higher ESR (P=0.04), uric acid (P=0.004) vibration perception thresholds (VPT), and lower eGFR (P<0.001). BMI (P<0.001), waist index (P=0.01), FPG (P=0.013), HbA1c (P=0.005) and ALT (P<0.001) were significantly lower in patients with PVD. Multivariate analysis revealed age (P=0.04), high total cholesterol (P=0.038), low BMI (P=0.017), low VPT (P=0 031) and declining eGFR (p=0.006) to be independent predictors of PVD. CONCLUSION: Increasing age, total cholesterol levels, and VPT, together with declining renal function and lower BMI are independent predictors of PVD in a type 2 diabetic population with advanced microvascular disease. Knowledge of risk factors will help target preventive measures and treatment to subjects most susceptible to PVD.

Albuminuria and glomerular filtration rate in type 2 diabetes mellitus.

AIM: The aim of this paper was to analyze the relation between glomerular filtration rate (GFR) and albumin excretion rate (AER) in subjects with type 2 diabetes. METHODS: Three hundred thirteen type 2 diabetic patients attending Diabetes Centre, Malta, were studied between 2008 and 2009. GFR was estimated using the Modified Diet Renal Disease (MDRD) formula while two spot measurements of urinary AER were used to determine albuminuria. RESULTS: Forty-nine patients were hyperfiltrating, of whom 69% were normoalbuminuric, 24% microalbuminuric, and 6% macroalbuminuric; 229 subjects had normal eGFR; of these 67% were normoalbuminuric, 27% microalbuminuric and 6% macroalbuminuric; 35 subjects had eGFR<60mL/min/1.73 m2, of whom 43% were normoalbuminuric, 37% microalbuminuric and 20% macroalbuminuric. No association was found between eGFR and AER in subjects with hyperfiltration (P=0.39); however eGFR was strongly correlated with AER in subjects with eGFR <60ml/min/1.73 m2 (r= -0.376; P=0.026). In multinomial logistic regression analysis, eGFR was significantly associated with albuminuria in non-hyperfiltrating, but not in hyperfiltrating, subjects. CONCLUSION: Our data suggests that hyperfiltration and albuminuria occur independently of each other in the early stages of DN, but the decline in eGFR and albuminuria follow a parallel course in later stages of DN suggesting that they may share common pathophysiological mechanisms or they may be causally linked.

Dynamical configuration of binary near-Earth asteroid (66391) 1999 KW4.

Dynamical simulations of the coupled rotational and orbital dynamics of binary near-Earth asteroid 66391 (1999 KW4) suggest that it is excited as a result of perturbations from the Sun during perihelion passages. Excitation of the mutual orbit will stimulate complex fluctuations in the orbit and rotation of both components, inducing the attitude of the smaller component to have large variation within some orbits and to hardly vary within others. The primary's proximity to its rotational stability limit suggests an origin from spin-up and disruption of a loosely bound precursor within the past million years.

Y-chromosome and mtDNA polymorphisms in Iraq, a crossroad of the early human dispersal and of post-Neolithic migrations.

Analyses of mtDNA and Y-chromosome variation were performed in a sample of Iraqis, a scarcely investigated population of the "Fertile Crescent." A total of 216 mtDNAs were screened for the diagnostic RFLP markers of the main Eurasian and African haplogroups. A subset of these samples, whose HVS-I sequences were previously obtained, was also examined by high-resolution restriction analysis. The Y-chromosome variation was investigated in 139 subjects by using 17 biallelic markers and the 49a,f/Taq I system. For both uniparental systems, the large majority of the haplogroups observed in the Iraqi population are those (H, J, T, and U for the mtDNA, and J(xM172) and J-M172 for the Y chromosome) considered to have originated in the Middle East and to have later spread all over Western Eurasia. However, about 9% of the mtDNAs and 30% of the Y-chromosomes most likely represent arrivals from distant geographic regions. The different proportion of long-range genetic input observed for the mtDNA and the Y chromosome appears to indicate that events of gene flow to this area might have involved mainly males rather than females.

The 49a,f haplotype 11 is a new marker of the EU19 lineage that traces migrations from northern regions of the Black Sea.

Previous studies on human Y-chromosome polymorphisms in the European populations highlighted the high frequency of the 49a,f/TaqI haplotype 11 and of the Eu19 (M17) lineage in Eastern Europe. To better understand the origin and the evolution of the Eu19, and its relationship with 49a,f Ht11, this study surveyed 2,235 individuals (mainly from Europe and the Middle East) for the 49a,f Ht11 and for many biallelic markers defining the Eu19 lineage. As previously described, the highest frequency of Eu19 was found in Eastern Europe. All the Eu19 Y-chromosomes turned out to be 49a,f Ht11 or its derivatives, the distribution of which suggests that the Eu19/49a,f Ht11 emerged in Ukraine, probably in a Palaeolithic population. Thereafter, the spread of this lineage toward Europe, Asia, and India occurred at different waves over a few thousands years. At present this seems to indicate the influence of the Ukraine Palaeolithic groups in the gene pool of modern populations. For the first time it is possible to make inferences about the evolution of some haplotypes of the 49a,f system. In spite of its unknown molecular base, this is one of the first most informative polymorphisms of the Y chromosome.

Radar observations of asteroid 216 kleopatra

Radar observations of the main-belt, M-class asteroid 216 Kleopatra reveal a dumbbell-shaped object with overall dimensions of 217 kilometers by 94 kilometers by 81 kilometers (+/-25%). The asteroid's surface properties are consistent with a regolith having a metallic composition and a porosity comparable to that of lunar soil. Kleopatra's shape is probably the outcome of an exotic sequence of collisional events, and much of its interior may have an unconsolidated rubble-pile structure.