Cusp Catastrophe Models for Cognitive Workload and Fatigue in a Verbally Cued Pictorial Memory Task

Objective: The aim of this study was to evaluate two cusp catastrophe models for cognitive workload and fatigue. They share similar cubic polynomial structures but derive from different underlying processes and contain variables that contribute to flexibility with respect to load and the ability to compensate for fatigue. Background: Cognitive workload and fatigue both have a negative impact on performance and have been difficult to separate. Extended time on task can produce fatigue, but it can also produce a positive effect from learning or automaticity. Method: In this two-part experiment, 129 undergraduates performed tasks involving spelling, arithmetic, memory, and visual search. Results: The fatigue cusp for the central memory task was supported with the quantity of work performed and performance on an episodic memory task acting as the control parameters. There was a strong linear effect, however. The load manipulations for the central task were competition with another participant for rewards, incentive conditions, and time pressure. Results supported the workload cusp in which trait anxiety and the incentive manipulation acted as the control parameters. Conclusion: The cusps are generally better than linear models for analyzing workload and fatigue phenomena; practice effects can override fatigue. Future research should investigate multitasking and task sequencing issues, physical-cognitive task combinations, and a broader range of variables that contribute to flexibility with respect to load or compensate for fatigue. Applications: The new experimental medium and analytic strategy can be generalized to virtually any realworld cognitively demanding tasks. The particular results are generalizable to tasks involving visual search

In Vivo RNA Interference Screens Identify Regulators of Antiviral CD4+ and CD8+ T Cell Differentiation

SummaryClassical genetic approaches to examine the requirements of genes for T cell differentiation during infection are time consuming. Here we developed a pooled approach to screen 30–100+ genes individually in separate antigen-specific T cells during infection using short hairpin RNAs in a microRNA context (shRNAmir). Independent screens using T cell receptor (TCR)-transgenic CD4+ and CD8+ T cells responding to lymphocytic choriomeningitis virus (LCMV) identified multiple genes that regulated development of follicular helper (Tfh) and T helper 1 (Th1) cells, and short-lived effector and memory precursor cytotoxic T lymphocytes (CTLs). Both screens revealed roles for the positive transcription elongation factor (P-TEFb) component Cyclin T1 (Ccnt1). Inhibiting expression of Cyclin T1, or its catalytic partner Cdk9, impaired development of Th1 cells and protective short-lived effector CTL and enhanced Tfh cell and memory precursor CTL formation in vivo. This pooled shRNA screening approach should have utility in numerous immunological studies

HNF1B and Endometrial Cancer Risk: Results from the PAGE study

We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC) and the Women's Health Initiative (WHI) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931cases/3,755 controls). The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs) per allele and 95% confidence intervals (CIs) of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P≥0.21) or between studies (P≥0.70). The ORper allele was 0.82 (95% CI: 0.75, 0.89; P = 5.63×10−6) for rs4430796 (G allele) and 0.79 (95% CI: 0.73, 0.87; P = 3.77×10−7) for rs7501939 (A allele). The associations with the risk of Type I and Type II tumors were similar (P≥0.19). Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations

The Influence of Obesity-Related Single Nucleotide Polymorphisms on BMI Across the Life Course: The PAGE Study

Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18–100 years, from multiple U.S. studies in the Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18–25 years), adulthood (ages 26–49 years), middle-age adulthood (ages 50–69 years), and older adulthood (ages ≥70 years); or 2) by menopausal status in women and stratification by age 50 years in men. Summary-effect estimates from each meta-analysis were compared for heterogeneity across the life epochs. We found heterogeneity in the association of the FTO (rs8050136) variant with BMI across the four adulthood epochs (P = 0.0006), with larger effects in young adults relative to older adults (β [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/m2, respectively, per A allele) and smaller intermediate effects. We found no evidence for heterogeneity in the association of GNPDA2, MTCH2, TMEM18, and NEGR1 with BMI across adulthood. Genetic predisposition to obesity may have greater effects on body weight in young compared with older adulthood for FTO, suggesting changes by age, generation, or secular trends. Future research should compare and contrast our findings with results using longitudinal data

An Informal Internet Survey on the Current State of Consciousness Science

The scientific study of consciousness emerged as an organized field of research only a few decades ago. As empirical results have begun to enhance our understanding of consciousness, it is important to find out whether other factors, such as funding for consciousness research and status of consciousness scientists, provide a suitable environment for the field to grow and develop sustainably. We conducted an online survey on people's views regarding various aspects of the scientific study of consciousness as a field of research. 249 participants completed the survey, among which 80% were in academia, and around 40% were experts in consciousness research. Topics covered include the progress made by the field, funding for consciousness research, job opportunities for consciousness researchers, and the scientific rigor of the work done by researchers in the field. The majority of respondents (78%) indicated that scientific research on consciousness has been making progress. However, most participants perceived obtaining funding and getting a job in the field of consciousness research as more difficult than in other subfields of neuroscience. Overall, work done in consciousness research was perceived to be less rigorous than other neuroscience subfields, but this perceived lack of rigor was not related to the perceived difficulty in finding jobs and obtaining funding. Lastly, we found that, overall, the global workspace theory was perceived to be the most promising (around 28%), while most non-expert researchers (around 22% of non-experts) found the integrated information theory (IIT) most promising. We believe the survey results provide an interesting picture of current opinions from scientists and researchers about the progresses made and the challenges faced by consciousness research as an independent field. They will inspire collective reflection on the future directions regarding funding and job opportunities for the field

An Informal Internet Survey on the Current State of Consciousness Science

The scientific study of consciousness emerged as an organized field of research only a few decades ago. As empirical results have begun to enhance our understanding of consciousness, it is important to find out whether other factors, such as funding for consciousness research and status of consciousness scientists, provide a suitable environment for the field to grow and develop sustainably. We conducted an online survey on people’s views regarding various aspects of the scientific study of consciousness as a field of research. 249 participants completed the survey, among which 80% were in academia, and around 40% were experts in consciousness research. Topics covered include the progress made by the field, funding for consciousness research, job opportunities for consciousness researchers, and the scientific rigor of the work done by researchers in the field. The majority of respondents (78%) indicated that scientific research on consciousness has been making progress. However, most participants perceived obtaining funding and getting a job in the field of consciousness research as more difficult than in other subfields of neuroscience. Overall, work done in consciousness research was perceived to be less rigorous than other neuroscience subfields, but this perceived lack of rigor was not related to the perceived difficulty in finding jobs and obtaining funding. Lastly, we found that, overall, the global workspace theory was perceived to be the most promising (around 28%), while most non-expert researchers (around 22% of non-experts) found the integrated information theory (IIT) most promising. We believe the survey results provide an interesting picture of current opinions from scientists and researchers about the progresses made and the challenges faced by consciousness research as an independent field. They will inspire collective reflection on the future directions regarding funding and job opportunities for the field