Background: There are urgent needs for rapid and accurate drug susceptibility testing of M. tuberculosis. GenoType MTBDRsl is a new molecular kit designed for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. In recent years, it has been evaluated in many settings, but with varied results. The aim of this meta-analysis was to synthesize the latest data on the diagnostic accuracy of GenoType MTBDRsl in detecting drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol, in comparison with the phenotypic drug susceptibility test. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search terms of "MTBDRsl" and "tuberculosis" were used on PubMed, EMBASE, and Web of Science. QUADAS-2 was used to assess the quality of included studies. Data were analyzed by Meta-Disc 1.4. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and corresponding 95% confidence interval (CI) for each study. From these calculations, forest plots and summary receiver operating characteristic (SROC) curves were produced. Results: Patient selection bias as well as flow and timing bias were observed in most studies. The summarized sensitivity (95% CI) was 0.874(0.845-0.899), 0.826(0.777-0.869), 0.820(0.772-0.862), 0.444(0.396-0.492), and 0.679(0.652-0.706) for fluoroquinolones, amikacin, capreomycin, kanamycin, and ethambutol, respectively. The specificity (95% CI) was 0.971(0.961-0.980), 0.995(0.987-0.998), 0.973(0.963-0.981), 0.993(0.985-0.997), and 0.799(0.773-0.823), respectively. The AUC (standard error) were 0.9754(0.0203), 0.9300(0.0598), 0.9885(0.0038), 0.9689(0.0359), and 0.6846(0.0550), respectively. Conclusion: Genotype MTBDRsl showed good accuracy for detecting drug resistance to fluoroquinolones, amikacin and capreomycin, but it may not be an appropriate choice for kanamycin and ethambutol. The lack of data did not allow for proper evaluation of the test on clinical specimens. Further systematic assessment of diagnostic performance should be carried out on direct clinical samples.

Schizophrenia is a chronic and debilitating psychiatric condition affecting slightly more than 1% of the population worldwide and it is a multifactorial disorder with a high degree of heritability (80%) based on family and twin studies. Increasing lines of evidence suggest intermediate phenotypes/endophenotypes are more associated with causes of the disease and are less genetically complex than the broader disease spectrum. Negative symptoms in schizophrenia are attractive intermediate phenotypes based on their clinical and treatment response features. Therefore, our objective was to identify genetic variants underlying the negative symptoms of schizophrenia by analyzing two genome-wide association (GWA) data sets consisting of a total of 1,774 European-American patients and 2,726 controls. Logistic regression analysis of negative symptoms as a binary trait (adjusted for age and sex) was performed using PLINK. For meta-analysis of two datasets, the fixed-effect model in PLINK was applied. Through meta-analysis we identified 25 single nucleotide polymorphisms (SNPs) associated with negative symptoms with p<5×10-5. Especially we detected five SNPs in the first two genes/loci strongly associated with negative symptoms of schizophrenia (Pmeta-analysis<6.22×10-6), which included three SNPs in the BCL9 gene: rs583583 showed the strongest association at a Pmeta-analysis of 6.00×10-7 and two SNPs in the C9orf5 (the top SNP is rs643410 with a p = 1.29 ×10-6). Through meta-analysis, we identified several additional negative symptoms associated genes (ST3GAL1, RNF144, CTNNA3 and ZNF385D). This is the first report of the common variants influencing negative symptoms of schizophrenia. These results provide direct evidence of using of negative symptoms as an intermediate phenotype to dissect the complex genetics of schizophrenia. However, additional studies are warranted to examine the underlying mechanisms of these disease-associated SNPs in these genes.

Objective: In the present study, we scanned the whole exome in three independent samples to search for replicable risk non synonymous (ns) variants (ns single-nucleotide polymorphisms [nsSNPs]) for alcohol dependence. Method: A total of 10,554 subjects in three independent samples were analyzed for association with alcohol dependence, including one European American sample (1,409 cases with alcohol dependence and 1,518 controls), one African American sample (681 cases and 508 controls), and one European Australian sample (a total of 6,438 family subjects with 1,645 alcohol-dependent probands). RNA expression of the risk genes in human, mouse, and rat brains was also explored. Results: We identified a total of 70 nsSNPs at 65 genes with nominally replicable associations; 22 nsSNPs at 21 genes among them survived corrections for multiple testing in meta-analysis (α =.0007). By incorporating the information from bioinformatics and RNA expression analyses, we identified at least two of the most promising risk genes for alcohol dependence: APOER2 and UBAP2. Conclusions: The gene coding for apolipoprotein E receptor 2 (APOER2) and the gene coding for ubiquitin associated protein-2 (UBAP2) are among the most appropriate for follow-up in human and nonhuman species as contributors to risk for alcohol dependence.

No description available.

The paleoclimate of the late Pliocene Longmen flora from Yongping County located at the southeastern boundary of the Qinghai-Tibet Plateau was reconstructed using two leaf-physiognomy-based methods, i.e., leaf margin analysis (LMA) and Climate Leaf Analysis Multivariate Program (CLAMP), to understand the paleoclimate condition and geographical pattern of monsoonal climate in southwestern China during the late Pliocene. The mean annual temperatures (MATs) estimated by LMA and CLAMP are 17.4 ± 3.3 C and 17.4 ± 1.3 C, respectively, compared with 15.9 C at present. Meanwhile, the growing season precipitation (GSP) estimated by CLAMP is 1735.5 ± 217.7 mm in the Longmen flora, compared with 986.9 mm nowadays. The calculated monsoon intensity index (MSI) of the Longmen flora is significantly lower than that of today. These results appear consistent with previous studies on the late Pliocene floras in western Yunnan based on the coexistence approach (CA), and further suggest that there was a slightly warmer and much wetter climate during the late Pliocene than the present climate in western Yunnan. We conclude that the significant change of the monsoonal climate might have been resulted from the continuous uplift of mountains in western Yunnan, as well as the intensification of the eastern Asian winter monsoon, both occurring concurrently in the post-Pliocene period.

Humans express at least seven alcohol dehydrogenase (ADH) isoforms that are encoded by ADH gene cluster (ADH7-ADH1C-ADH1B-ADH1A-ADH6-ADH4-ADH5) at chromosome 4. ADHs are key catabolic enzymes for retinol and ethanol. The functional ADH variants (mostly rare) have been implicated in alcoholism risk. In addition to catalyzing the oxidation of retinol and ethanol, ADHs may be involved in the metabolic pathways of several neurotransmitters that are implicated in the neurobiology of neuropsychiatric disorders. In the present study, we comprehensively examined the associations between common ADH variants [minor allele frequency (MAF) >0.05] and 11 neuropsychiatric and neurological disorders. A total of 50,063 subjects in 25 independent cohorts were analyzed. The entire ADH gene cluster was imputed across these 25 cohorts using the same reference panels. Association analyses were conducted, adjusting for multiple comparisons. We found 28 and 15 single nucleotide polymorphisms (SNPs), respectively, that were significantly associated with schizophrenia in African-Americans and autism in European-Americans after correction by false discovery rate (FDR) (q < 0.05); and 19 and 6 SNPs, respectively, that were significantly associated with these two disorders after region-wide correction by SNPSpD (8.9 × 10-5 ≤ p ≤ 0.0003 and 2.4 × 10-5 ≤ p ≤ 0.0003, respectively). No variants were significantly associated with the other nine neuropsychiatric disorders, including alcohol dependence. We concluded that common ADH variants conferred risk for both schizophrenia in African-Americans and autism in European-Americans.

Background: There are urgent needs for rapid and accurate drug susceptibility testing of M. tuberculosis. GenoType MTBDRsl is a new molecular kit designed for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. In recent years, it has been evaluated in many settings, but with varied results. The aim of this meta-analysis was to synthesize the latest data on the diagnostic accuracy of GenoType MTBDRsl in detecting drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol, in comparison with the phenotypic drug susceptibility test. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search terms of "MTBDRsl" and "tuberculosis" were used on PubMed, EMBASE, and Web of Science. QUADAS-2 was used to assess the quality of included studies. Data were analyzed by Meta-Disc 1.4. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and corresponding 95% confidence interval (CI) for each study. From these calculations, forest plots and summary receiver operating characteristic (SROC) curves were produced. Results: Patient selection bias as well as flow and timing bias were observed in most studies. The summarized sensitivity (95% CI) was 0.874(0.845-0.899), 0.826(0.777-0.869), 0.820(0.772-0.862), 0.444(0.396-0.492), and 0.679(0.652-0.706) for fluoroquinolones, amikacin, capreomycin, kanamycin, and ethambutol, respectively. The specificity (95% CI) was 0.971(0.961-0.980), 0.995(0.987-0.998), 0.973(0.963-0.981), 0.993(0.985-0.997), and 0.799(0.773-0.823), respectively. The AUC (standard error) were 0.9754(0.0203), 0.9300(0.0598), 0.9885(0.0038), 0.9689(0.0359), and 0.6846(0.0550), respectively. Conclusion: Genotype MTBDRsl showed good accuracy for detecting drug resistance to fluoroquinolones, amikacin and capreomycin, but it may not be an appropriate choice for kanamycin and ethambutol. The lack of data did not allow for proper evaluation of the test on clinical specimens. Further systematic assessment of diagnostic performance should be carried out on direct clinical samples.

Schizophrenia is a chronic and debilitating psychiatric condition affecting slightly more than 1% of the population worldwide and it is a multifactorial disorder with a high degree of heritability (80%) based on family and twin studies. Increasing lines of evidence suggest intermediate phenotypes/endophenotypes are more associated with causes of the disease and are less genetically complex than the broader disease spectrum. Negative symptoms in schizophrenia are attractive intermediate phenotypes based on their clinical and treatment response features. Therefore, our objective was to identify genetic variants underlying the negative symptoms of schizophrenia by analyzing two genome-wide association (GWA) data sets consisting of a total of 1,774 European-American patients and 2,726 controls. Logistic regression analysis of negative symptoms as a binary trait (adjusted for age and sex) was performed using PLINK. For meta-analysis of two datasets, the fixed-effect model in PLINK was applied. Through meta-analysis we identified 25 single nucleotide polymorphisms (SNPs) associated with negative symptoms with p<5×10-5. Especially we detected five SNPs in the first two genes/loci strongly associated with negative symptoms of schizophrenia (Pmeta-analysis<6.22×10-6), which included three SNPs in the BCL9 gene: rs583583 showed the strongest association at a Pmeta-analysis of 6.00×10-7 and two SNPs in the C9orf5 (the top SNP is rs643410 with a p = 1.29 ×10-6). Through meta-analysis, we identified several additional negative symptoms associated genes (ST3GAL1, RNF144, CTNNA3 and ZNF385D). This is the first report of the common variants influencing negative symptoms of schizophrenia. These results provide direct evidence of using of negative symptoms as an intermediate phenotype to dissect the complex genetics of schizophrenia. However, additional studies are warranted to examine the underlying mechanisms of these disease-associated SNPs in these genes.

Objective: In the present study, we scanned the whole exome in three independent samples to search for replicable risk non synonymous (ns) variants (ns single-nucleotide polymorphisms [nsSNPs]) for alcohol dependence. Method: A total of 10,554 subjects in three independent samples were analyzed for association with alcohol dependence, including one European American sample (1,409 cases with alcohol dependence and 1,518 controls), one African American sample (681 cases and 508 controls), and one European Australian sample (a total of 6,438 family subjects with 1,645 alcohol-dependent probands). RNA expression of the risk genes in human, mouse, and rat brains was also explored. Results: We identified a total of 70 nsSNPs at 65 genes with nominally replicable associations; 22 nsSNPs at 21 genes among them survived corrections for multiple testing in meta-analysis (α =.0007). By incorporating the information from bioinformatics and RNA expression analyses, we identified at least two of the most promising risk genes for alcohol dependence: APOER2 and UBAP2. Conclusions: The gene coding for apolipoprotein E receptor 2 (APOER2) and the gene coding for ubiquitin associated protein-2 (UBAP2) are among the most appropriate for follow-up in human and nonhuman species as contributors to risk for alcohol dependence.

Non-parametric methods such as Wilcoxon test have the advantages of no assumptions for the underlying survival distributions. Alzheimer’s disease (AD) is a chronic neurodegenerative disease while the ectopic P-granules autophagy protein 5 homolog (EPG5 gene) is highly expressed in human brain and may implicate in the pathogenesis of neurodegenerative disorders. The present study explored the associations of 26 single-nucleotide polymorphisms (SNPs) in the EPG5 gene with the age at onset (AAO) of AD using a family-based association test (FBAT)-Wilcoxon statistic in a family-based study. Then a replication study using a case-control sample was conducted to perform Wilcoxon test in Kaplan–Meier survival analysis of AAO. The results from FBAT-generalized estimating equations (FBAT-GEE) statistics and FBAT-Wilcoxon test showed that seven SNPs (top SNP rs495078 with p = 1.29 × 10−3) were significantly associated with the risk of AD, and eight SNPs (top SNP rs11082498 with p = 3.55 × 10−4) were associated with the AAO of AD in the family-based study (p < 0.05). In the replicated data, three SNPs were associated with AAO by using the Wilcoxon test, where the mean AAO was approximately 2.2 years earlier in individuals who had at least one minor allele of the top AAO-associated SNP rs9963463 (p = 0.0018) compared with those who were homozygous for the major allele. These findings from non-parametric survival analyses provide evidence for several genetic variants in EPG5 influencing the AAO of AD and will serve as a resource for replication in other populations.