Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n = 109,122 individuals. We identified 59 sentinel variants (p < 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that the independent signals colocalized with cell-type-specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes

Neural correlates of visuomotor adjustments during scaling of human finger movements

Visually guided finger movements include online feedback of current effector position to guide target approach. This visual feedback may be scaled or otherwise distorted by unpredictable perturbations. Although adjustments to visual feedback scaling have been studied before, the underlying brain activation differences between upscaling (visual feedback larger than real movement) and downscaling (feedback smaller than real movement) are currently unknown. Brain activation differences between upscaling and downscaling might be expected because within-trial adjustments during upscaling require corrective backwards accelerations, whereas correcting for downscaling requires forward accelerations. In this behavioural and fMRI study we investigated adjustments during up- and downscaling in a target-directed finger flexion-extension task with real-time visual feedback. We found that subjects made longer and more complete within-trial corrections for downscaling perturbations than for upscaling perturbations. The finger task activated primary motor (M1) and somatosensory (S1) areas, premotor and parietal regions, basal ganglia, and cerebellum. General scaling effects were seen in the right pre-supplementary motor area, dorsal anterior cingulate cortex, inferior parietal lobule, and dorsolateral prefrontal cortex. Stronger activations for down- than for upscaling were observed in M1, supplementary motor area (SMA), S1 and anterior cingulate cortex. We argue that these activation differences may reflect differing online correction for upscaling versus downscaling during finger flexion-extension

Guideline implementation for breast healthcare in low- and middle-income countries: early detection resource allocation.

A key determinant of breast cancer outcome in any population is the degree to which cancers are detected at early stages of disease. Populations in which cancers are detected at earlier stages have lower breast cancer mortality rates. The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary in October 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for early detection, diagnosis, and treatment in low- and middle-income countries (LMCs). A multidisciplinary panel of experts specifically addressed the implementation of BHGI guidelines for the early detection of disease as they related to resource allocation for public education and awareness, cancer detection methods, and evaluation goals. Public education and awareness are the key first steps, because early detection programs cannot be successful if the public is unaware of the value of early detection. The effectiveness and efficiency of screening modalities, including screening mammography, clinical breast examination (CBE), and breast self-examination, were reviewed in the context of resource availability and population-based need by the panel. Social and cultural barriers should be considered when early detection programs are being established, and the evaluation of early detection programs should include the use of well developed, methodologically sound process metrics to determine the effectiveness of program implementation. The approach and scope of any screening program will determine the success of any early detection program as measured by cancer stage at diagnosis and will drive the breadth of resource allocation needed for program implementation

Anatomic MR imaging and functional diffusion tensor imaging of peripheral nerve tumors and tumorlike conditions

BACKGROUND AND PURPOSE:A number of benign and malignant peripheral nerve tumor and tumorlike conditions produce similar imaging features on conventional anatomic MR imaging. Functional MR imaging using DTI can increment the diagnostic performance in differentiation of these lesions. Our aim was to evaluate the role of 3T anatomic MR imaging and DTI in the characterization of peripheral nerve tumor and tumorlike conditions.MATERIALS AND METHODS:Twenty-nine patients (13 men, 16 women; mean age, 41 ± 18 years; range, 11-83 years) with a nerve tumor or tumorlike condition (25 benign, 5 malignant) underwent 3T MR imaging by using anatomic (n = 29), functional diffusion, DWI (n = 21), and DTI (n = 24) techniques. Images were evaluated for image quality (3-point scale), ADC of the lesion, tractography, and fractional anisotropy of nerves with interobserver reliability in ADC and FA measurements.RESULTS:No significant differences were observed in age (benign, 40 ± 18 versus malignant, 45 ± 19 years) and sex (benign, male/female = 12:12 versus malignant, male/female = 3:2) (P > .05). All anatomic (29/29, 100%) MR imaging studies received "good" quality; 20/21 (95%) DWI and 21/24 (79%) DTI studies received "good" quality. ADC of benign lesions (1.848 ± 0.40 × 10(-3) mm(2)/s) differed from that of malignant lesions (0.900 ± 0.25 × 10(-3) mm(2)/s, P .05). FA of involved nerves was lower than that in contralateral healthy nerves (P .05), with excellent intermethod reliability (ICC = 0.943 [95% CI, 0.836-0.980]). Tractography differences were observed in benign and malignant lesions.CONCLUSIONS:3T MR imaging and DTI are valuable methods for anatomic and functional evaluation of peripheral nerve lesions with excellent interobserver reliability. While tractography and low FA provide insight into neural integrity, low diffusivity values indicate malignancy in neural masses

A compact quantum-cascade laser based spectrometer for monitoring the concentrations of methane and nitrous oxide in the troposphere

A spectrometer, based on the frequency down-chirped radiation from a pulsed quantum-cascade laser, capable of detecting fluctuations in local ground level methane and nitrous oxide concentrations over a time scale of minutes, is presented. The applicability of this instrument to low-level atmospheric detection is demonstrated through sampling gases in two locations

Consensus statement on essential patient characteristics in systemic treatment trials for metastatic colorectal cancer: Supported by the ARCAD Group

Available online 22 June 2018Abstract not availableKaitlyn K.H. Goey ... Timothy J. Price ... et al