Carol Barnes: A Prominent Voice in the Neuroscience of Aging, and a Proponent of Women in Neuroscience

Dr. Barnes, as a professor and a graduate mentor, is constantly in contact with the new generation of women neuroscientists, helping shape their future career paths and providing them with an uncountable number of resources. Barnes’ research is centered on the changes that happen in learning, memory and behavior in normal aging, rather than in neurological diseases

Personality Factors Associated with Success or Failure on the United States Medical Licensing Examination Step 1 (USMLE Step 1)

Failure of medical students to pass Step 1 of the United States Medical Licensing Examination (USMLE Step 1) can create psychological, academic and financial crises for the students, educational institutions and, ultimately, the public by negatively influencing the cost of health care. Medical students from the University of Kansas School of Medicine (n = 377) and from varying United States of America medical schools enrolled at the University of Missouri, Kansas City, Institute for Professional Preparation (n = 109) had participated voluntarily in ongoing research data gathering. Results from this voluntary testing with the Myers-Briggs Type Indicator (MBTI), the Adult Personality Inventory (API) and self-report demographic data questionnaire for Ethnicity/Race and Gender were examined for personality factor variables appearing to be associated with success or failure by medical students on the USMLE Step 1. The goal was to facilitate future targeting of possibly “at risk” students for preventive academic review and psychological bolstering. Statistical analyses were performed on the data by running contingency analyses, univariate F tests, discriminant function analyses, Chi-square and correlation analyses. Results indicated that subjects who passed the USMLE Step 1 scored higher on the API in the areas of Competitive and Extraverted and lower on Enterprising, while being characterized by the Thinking orientation of the MBTI. Further, those who passed were more likely to be male and Caucasian/White and significantly less likely to be Black. Those who failed the USMLE Step 1 tended to score higher on the API Enterprising and lower on Competitive and Extraverted, while being characterized by the MBTI Feeling orientation. Additionally, those who failed tended to be Black, female and were less likely to be Caucasian/White. 86.0% of cases were correctly classified by the function. Suggestions for counseling practice, proactive or immediate interventions, and implications for future research are discussed in light of these results

Pengendalian dan Perbaikan Kualitas Proses Printing Kemasan Produk Menggunakan Integrasi FMEA-TRIZ

Kemasan produk telah memainkan peran penting sebagai wadah penyimpanan produk. Problem dalam kualitas produk kemasan adalah sering terjadi defect yang melebihi target perusahaan dalam proses produksi dan dapat menimbulkan komplain dari customer. Cara untuk mereduksi defect yang terjadi adalah dengan pengendalian kualitas pada tingkat proses. Penelitian ini menggunakan Six Sigma sebagai acuan proses perbaikan dengan menggunakan tahapan alur Define, Measure, Analyze, Improve, Control (DMAIC). Tahap define meliputi pendefinisian objek, pembuatan operation process chart (OPC), critical proses, critical to quality (CTQ) serta menentukan prioritas defect menggunakan pareto chart. Tahap measure menggunakan Kapabilitas Proses dan DPMO untuk mengetahui kinerja proses. Tahap Analyze digunakan FMEA untuk mendapatkan prioritas penyebab kegagalan produk dalam critical proses, kemudian dilakukan integrasi menggunakan TRIZ dalam tahap improve untuk mendapatkan rekomendasi perbaikan yang cocok dalam pengembangan critical proses. Lalu dilakukan penerapan mekanisme control. Hasil penelitian menunjukkan proses printing merupakan critical proses dengan nilai DPMO 18372 serta critical defect yaitu defect miss print, garis, dan warna. Level Sigma perusahaan berada pada 3,58 sigma dan nilai Kapabilitas proses adalah 1,19. Adapun Hasil FMEA, untuk miss print disebabkan komponen cylinder yaitu gear dan bearing tidak presisi, untuk defect warna disebabkan komposisi tinta dan defect garis disebabkan tinta bagus tercampur tinta. Berdasarkan analisa contradiction matrix dan 40 inventive principle, rekomendasi perbaikan untuk proses printing dengan defect miss print yaitu melakukan pembersihan komponen gear Box menggunakan vacuum cleaner, bantuan alat vibration tester dan penambahan lock nut, untuk Defect warna melakukan pelatihan takaran viskositas dan strategi pengembangan supplier, untuk defect garis dengan pemasangan kamera di station printing dan pembersihan secara periodik di saluran pompa tinta ======================================================================================================= Product packaging has played an important role in a storage container product. Problems in the quality of packaging products is often a defect that exceeds the target company in the production process and can cause complaints from customers. A way to reduce defects that occur is the quality control at the level of the process. This research uses the Six Sigma process improvement as a reference using the stages of DMAIC. The step of definition object, include define manufacturing operation process chart, identification of defects, critical process, critical to quality as well as determine priority defects using the pareto chart. Phase measure using the Capability process and DPMO to know the performance of the process. The step of analyzing use FMEA to get priority causes failure of the products in the process, then improve used by integration the method of TRIZ to get suitable recommendations. Then apply the control mechanism. The results showed the process of printing is a critical process with the value of the DPMO 18372 Sigma Level, level sigma for the plant is 1.58 sigma and the capability of the process is 1,19. The results of FMEA, for critical defects miss print caused by the component of the cylinder, imprecision of gear and bearing, for color defects caused by the composition of ink and line defects caused by great mixed dried ink. Based on the analysis of contradiction matrix and 40 inventive principles, recommendations to repair defects miss print that is cleaning component of the gearbox using a vacuum cleaner, help tool vibration tester and the addition of the lock nut, for the colors of Defect apply training to measure the viscosity and the development strategy of the supplier. Line defects adding CCTV in station printing and periodic cleaning of the ink pum

Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes

AIM: Substance use disorders (SUD) result in substantial morbidity and mortality worldwide. Opioids, and to a lesser extent cocaine, contribute to a large percentage of this health burden. Despite their high heritability, few genetic risk loci have been identified for either opioid or cocaine dependence (OD or CD, respectively). A genome-wide association study of OD and CD related phenotypes reflecting the time between first self-reported use of these substances and a first DSM-IV dependence diagnosis was conducted. METHODS: Cox proportional hazards regression in a discovery sample of 6,188 African-Americans (AAs) and 6,835 European-Americans (EAs) participants in a genetic study of multiple substance dependence phenotypes were used to test for association between genetic variants and these outcomes. The top findings were tested for replication in two independent cohorts. RESULTS: In the discovery sample, three independent regions containing variants associated with time to dependence at CONCLUSIONS: Although the two GWS variants are not in genes with obvious links to SUD biology and have modest effect sizes, they are statistically robust and show evidence for association in independent samples. These results may point to novel pathways contributing to disease progression and highlight the utility of related phenotypes to better understand the genetics of SUDs

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Genome-wide association study of opioid cessation

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for \u3e1 year or \u3c6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 i

Genome-wide association study of stimulant dependence

Stimulant dependence is heritable, but specific genetic factors underlying the trait have not been identified. A genome-wide association study for stimulant dependence was performed in a discovery cohort of African- (AA) and European-ancestry (EA) subjects ascertained for genetic studies of alcohol, opioid, and cocaine use disorders. The sample comprised individuals with DSM-IV stimulant dependence (393 EA cases, 5288 EA controls; 155 AA cases, 5603 AA controls). An independent cohort from the family-based Collaborative Study on the Genetics of Alcoholism (532 EA cases, 7635 EA controls; 53 AA cases, AA 3352 controls) was used for replication. One variant in SLC25A16 (rs2394476, p = 3.42 × 10-10, odds ratio [OR] = 3.70) was GWS in AAs. Four other loci showed suggestive evidence, including KCNA4 in AAs (rs11500237, p = 2.99 × 10-7, OR = 2.31) which encodes one of the potassium voltage-gated channel protein that has been linked to several other substance use disorders, and CPVL in the combined population groups (rs1176440, p = 3.05 × 10-7, OR = 1.35), whose expression was previously shown to be upregulated in the prefrontal cortex from users of cocaine, cannabis, and phencyclidine. Analysis of the top GWAS signals revealed a significant enrichment with nicotinic acetylcholine receptor genes (adjusted p = 0.04) and significant pleiotropy between stimulant dependence and alcohol dependence in EAs (padj = 3.6 × 10-3), an anxiety disorder in EAs (padj = 2.1 × 10-4), and ADHD in both AAs (padj = 3.0 × 10-33) and EAs (padj = 6.7 × 10-35). Our results implicate novel genes and pathways as having roles in the etiology of stimulant dependence

ACSL6 Is Associated with the Number of Cigarettes Smoked and Its Expression Is Altered by Chronic Nicotine Exposure

Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS) sample showed similar pattern of association with number of cigarettes smoked per day (numCIG) for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n\u3e16,000) for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively) but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day) exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression ofACSL6 requires nicotinic receptor activation. These findings suggest that variations in theACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions

Genetic risk prediction and neurobiological understanding of alcoholism

We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder and schizophrenia. A panel of all the nominally significant P-value single-nucleotide length polymorphisms (SNPs) in the top candidate genes discovered by CFG (n = 135 genes, 713 SNPs) was used to generate a genetic risk prediction score (GRPS), which showed a trend towards significance (P = 0.053) in separating alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and subsequently tested them in three independent cohorts, from two continents. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP) knockout mouse, consistent with the surfeit of stress theory of addiction proposed by Koob and colleagues. A much smaller panel (n = 11 genes, 66 SNPs) of the top CFG-discovered genes for alcoholism, cross-validated and prioritized by this stress-reactive animal model showed better predictive ability in the independent German test cohort (P = 0.041). The top CFG scoring gene for alcoholism from the initial discovery step, synuclein alpha (SNCA) remained the top gene after the stress-reactive animal model cross-validation. We also tested this small panel of genes in two other independent test cohorts from the United States, one with alcohol dependence (P = 0.00012) and one with alcohol abuse (a less severe form of alcoholism; P = 0.0094). SNCA by itself was able to separate alcoholics from controls in the alcohol-dependent cohort (P = 0.000013) and the alcohol abuse cohort (P = 0.023). So did eight other genes from the panel of 11 genes taken individually, albeit to a lesser extent and/or less broadly across cohorts. SNCA, GRM3 and MBP survived strict Bonferroni correction for multiple comparisons. Taken together, these results suggest that our stress-reactive DBP animal model helped to validate and prioritize from the CFG-discovered genes some of the key behaviorally relevant genes for alcoholism. These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination) and cocaine addiction. Overall, our work provides leads towards a better understanding of illness, diagnostics and therapeutics, including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder, schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape