Are conscious perception and action guidance dissociable in whole-body movement?

Conscious recognition of an object (“what”) and guidance of action toward it (“how”) have been identified as two dissociable processes of perception in visual, auditory, and somatosensory systems. The current study investigated whether the two dissociable processes of perception can also be observed in whole-body movements that encompass not only somatosensory (proprioceptive) inputs but also vestibular inputs.https://engagedscholarship.csuohio.edu/u_poster_2012/1014/thumbnail.jp

Mediation analysis for a survival outcome with time-varying exposures, mediators, and confounders

We propose an approach to conduct mediation analysis for survival data with time-varying exposures, mediators, and confounders. We identify certain interventional direct and indirect effects through a survival mediational g-formula and describe the required assumptions. We also provide a feasible parametric approach along with an algorithm and software to estimate these effects. We apply this method to analyze the Framingham Heart Study data to investigate the causal mechanism of smoking on mortality through coronary artery disease. The risk ratio of smoking 30 cigarettes per day for ten years compared with no smoking on mortality is 2.34 (95 % CI = (1.44, 3.70)). Of the overall effect, 7.91% (95% CI: = 1.36%, 19.32%) is mediated by coronary artery disease. The survival mediational g-formula constitutes a powerful tool for conducting mediation analysis with longitudinal data

Activation of minority-variant Plasmodium vivax hypnozoites following artesunate + amodiaquine treatment in a 23-year old man with relapsing malaria in Antananarivo, Madagascar

In endemic areas, Plasmodium vivax relapses are difficult to distinguish from new infections. Genotyping of patients who experience relapse after returning to a malaria-free area can be used to explore the nature of hypnozoite activation and relapse. This paper describes a person who developed P. vivax malaria for the first time after travelling to Boriziny in the malaria endemic coastal area of Madagascar, then suffered two P. vivax relapses 11 weeks and 21 weeks later despite remaining in Antananarivo in the malaria-free central highlands area. He was treated with the combination artesunate + amodiaquine according to the national malaria policy in Madagascar. Genotyping by PCR-RFLP at pvmsp-3α as well as pvmsp1 heteroduplex tracking assay (HTA) showed the same dominant genotype at each relapse. Multiple recurring minority variants were also detected at each relapse, highlighting the propensity for multiple hypnozoite clones to activate simultaneously to cause relapse

Identification of presumed pathogenic KRT3 and KRT12 gene mutations associated with Meesmann corneal dystrophy.

PurposeTo report potentially pathogenic mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes in two individuals with clinically diagnosed Meesmann corneal dystrophy (MECD).MethodsSlit-lamp examination was performed on the probands and available family members to identify characteristic features of MECD. After informed consent was obtained, saliva samples were obtained as a source of genomic DNA, and screening of KRT3 and KRT12 was performed. Potentially pathogenic variants were screened for in 200 control chromosomes. PolyPhen-2, SIFT, and PANTHER were used to predict the functional impact of identified variants. Short tandem repeat genotyping was performed to confirm paternity.ResultsSlit-lamp examination of the first proband demonstrated bilateral, diffusely distributed, clear epithelial microcysts, consistent with MECD. Screening of KRT3 revealed a heterozygous missense variant in exon 1, c.250C>T (p.(Arg84Trp)), which has a minor allele frequency of 0.0076 and was not identified in 200 control chromosomes. In silico analysis with PolyPhen-2 and PANTHER predicted the variant to be damaging to protein function; however, SIFT analysis predicted tolerance of the variant. The second proband demonstrated bilateral, diffusely distributed epithelial opacities that appeared gray-white on direct illumination and translucent on retroillumination. Neither parent demonstrated corneal opacities. Screening of KRT12 revealed a novel heterozygous insertion/deletion variant in exon 6, c.1288_1293delinsAGCCCT (p.(Arg430_Arg431delinsSerPro)). This variant was not present in either of the proband's parents or in 200 control chromosomes and was predicted to be damaging by PolyPhen-2, PANTHER, and SIFT. Haplotype analysis confirmed paternity of the second proband, indicating that the variant arose de novo.ConclusionsWe present a novel KRT12 mutation, representing the first de novo mutation and the first indel in KRT12 associated with MECD. In addition, we report a variant of uncertain significance in KRT3 in an individual with MECD. Although the potential pathogenicity of this variant is unknown, it is the first variant affecting the head domain of K3 to be reported in an individual with MECD and suggests that disease-causing variants associated with MECD may not be restricted to primary sequence alterations of either the helix-initiation or helix-termination motifs of K3 and K12

Key Knowledge Gaps for Plasmodium vivax Control and Elimination

There is inadequate understanding of the biology, pathology, transmission, and control of Plasmodium vivax, the geographically most widespread cause of human malaria. During the last decades, study of this species was neglected, in part due to the erroneous belief that it is intrinsically benign. In addition, many technical challenges in culturing the parasite also hampered understanding its fundamental biology and molecular and cellular responses to chemotherapeutics. Research on vivax malaria needs to be substantially expanded over the next decade to accelerate its elimination and eradication. This article summarizes key knowledge gaps identified by researchers, national malaria control programs, and other stakeholders assembled by the World Health Organization to develop strategies for controlling and eliminating vivax malaria. The priorities presented in this article emerged in these technical discussions, and were adopted by expert consensus of the authors. All involved understood the priority placed upon pragmatism in this research agenda, that is, focus upon tools delivering better prevention, diagnosis, treatment, and surveillance of P. vivax

Rapid detection of BRCA1/2 recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels.

BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS). BRCA mutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novel BRCA2 mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC

Phase 1 Study of High-Specific-Activity I-131 MIBG for Metastatic and/or Recurrent Pheochromocytoma or Paraganglioma

Context: No therapies are approved for the treatment of metastatic and/or recurrent pheochromocytoma or paraganglioma (PPGL) in the United States. Objective: To determine the maximum tolerated dose (MTD) of high-specific-activity I-131 meta-iodobenzylguanidine (MIBG) for the treatment of metastatic and/or recurrent PPGL. Design: Phase 1, dose-escalating study to determine the MTD via a standard 3 + 3 design, escalating by 37 MBq/kg starting at 222 MBq/kg. Setting: Three centers. Patients: Twenty-one patients were eligible, received study drug, and were evaluable for MTD, response, and toxicity. Intervention: Open-label use of high-specific-activity I-131 MIBG therapy. Main Outcome Measures: Dose-limiting toxicities, adverse events, radiation absorbed dose estimates, radiographic tumor response, biochemical response, and survival. Results: The MTD was determined to be 296 MBq/kg on the basis of two observed dose-limiting toxicities at the next dose level. The highest mean radiation absorbed dose estimates were in the thyroid and lower large intestinal wall (each 1.2 mGy/MBq). Response was evaluated by total administered activity: four patients (19%), all of whom received \u3e18.5 GBq of study drug, had radiographic tumor responses of partial response by Response Evaluation Criteria in Solid Tumors. Best biochemical responses (complete or partial response) for serum chromogranin A and total metanephrines were observed in 80% and 64% of patients, respectively. Overall survival was 85.7% at 1 year and 61.9% at 2 years after treatment. The majority (84%) of adverse events were considered mild or moderate in severity. Conclusions: These findings support further development of high-specific-activity I-131 MIBG for the treatment of metastatic and/or recurrent PPGL at an MTD of 296 MBq/kg

Models of human core transcriptional regulatory circuitries

A small set of core transcription factors (TFs) dominates control of the gene expression program in embryonic stem cells and other well-studied cellular models. These core TFs collectively regulate their own gene expression, thus forming an interconnected auto-regulatory loop that can be considered the core transcriptional regulatory circuitry (CRC) for that cell type. There is limited knowledge of core TFs, and thus models of core regulatory circuitry, for most cell types. We recently discovered that genes encoding known core TFs forming CRCs are driven by super-enhancers, which provides an opportunity to systematically predict CRCs in poorly studied cell types through super-enhancer mapping. Here, we use super-enhancer maps to generate CRC models for 75 human cell and tissue types. These core circuitry models should prove valuable for further investigating cell-type–specific transcriptional regulation in healthy and diseased cells.United States. National Institutes of Health (HG002668

Census of the Local Universe (CLU) Narrow-Band Survey I: Galaxy Catalogs from Preliminary Fields

We present the Census of the Local Universe (CLU) narrow-band survey to search for emission-line (\ha) galaxies. CLU-\ha~has imaged $\approx$3$\pi$ of the sky (26,470~deg$^2$) with 4 narrow-band filters that probe a distance out to 200~Mpc. We have obtained spectroscopic follow-up for galaxy candidates in 14 preliminary fields (101.6~deg$^2$) to characterize the limits and completeness of the survey. In these preliminary fields, CLU can identify emission lines down to an \ha~flux limit of $10^{-14}$~$\rm{erg~s^{-1}~cm^{-2}}$ at 90\% completeness, and recovers 83\% (67\%) of the \ha~flux from catalogued galaxies in our search volume at the $\Sigma$=2.5 ($\Sigma$=5) color excess levels. The contamination from galaxies with no emission lines is 61\% (12\%) for $\Sigma$=2.5 ($\Sigma$=5). Also, in the regions of overlap between our preliminary fields and previous emission-line surveys, we recover the majority of the galaxies found in previous surveys and identify an additional $\approx$300 galaxies. In total, we find 90 galaxies with no previous distance information, several of which are interesting objects: 7 blue compact dwarfs, 1 green pea, and a Seyfert galaxy; we also identified a known planetary nebula. These objects show that the CLU-\ha~survey can be a discovery machine for objects in our own Galaxy and extreme galaxies out to intermediate redshifts. However, the majority of the CLU-\ha~galaxies identified in this work show properties consistent with normal star-forming galaxies. CLU-\ha~galaxies with new redshifts will be added to existing galaxy catalogs to focus the search for the electromagnetic counterpart to gravitational wave events.Comment: 28 pages, 22 figures, 4 tables (Accepted to ApJ

Individual differences in mental toughness associate with academic performance and income

Mental toughness (MT) has been related to high performance in competitive situations. The current studies tested whether individual differences in MT were associated with success in two achievement domains: higher education and work. Academic performance and attendance were assessed over three years in a British university sample. MT was associated with higher average academic grades (Study 1). Individual differences in MT predicted individuals' income, controlling for age and gender (Study 2). The results suggest that MT entails positive psychological resources that are important for academic and career success. Future research aiming at exploring the factors that contribute to variation in MT and the mechanisms that underlie the association between MT and achievement may have significant implications for predicting and optimizing performance in various domains