Daisy Wang

Whole genome sequencing (WGS) is increasingly becoming a routine tool for the management of infectious diseases, and its implementation into public health systems requires careful consideration of the sociocultural context. High-resolution WGS data can provide insights into transmission sources and pathways, which presents privacy concerns and other ethical issues. We explored the ethical, legal, and social implications (ELSI) of WGS from the perspectives of public health professionals working with the technology in the context of a tuberculosis (TB) outbreak that occurred primarily among a Pasifika community in Victoria, Australia. We conducted qualitative, retrospective interviews with public health staff involved in the outbreak investigation to explore their perspectives on the ELSI associated with WGS. The interviews were iterative​ and thematic analysis was used to identify key themes. Sociocultural factors were central to the TB investigation. Public health staff worked closely with patients, families, and local churches to build trust, manage TB stigma, and facilitate access to TB education and healthcare. In this context, the ten interview participants highlighted the importance of considered and ethical implementation of WGS. Key ELSI themes ​were​: (1) trust and relationship-building as a foundation for successful outbreak response; (2) patient privacy and confidentiality; (3) appropriate language use to reduce stigma; 4) transparency and community engagement; (5) equity of benefits and risks; and (6) emerging legal considerations. Notably, thoughtful dialogue around WGS and the associated ELSI by public health staff could be used as a mechanism to build trust with patients. This study illustrates how public health professionals are actively navigating ELSI in practice. WGS implementation should build public trust through transparent WGS processes, strong privacy protections, the use of non-stigmatising language, and active community engagement. However, there is a lack of formal guidance or existing consensus to address ethical tensions. Robust ethical frameworks should be established through a formal consensus approach with the inclusion of community perspectives to enhance the responsible long-term implementation of WGS.

© 2015 Wiley Periodicals, Inc. One of the major findings from multimodal neuroimaging studies in the past decade is that the human brain is anatomically and functionally organized into large-scale networks. In resting state fMRI, spatial patterns emerge when temporal correlations between various brain regions are tallied, evidencing networks of ongoing intercortical cooperation. However, the dynamic structure governing the brain's spontaneous activity is far less understood due to the short and noisy nature of the rs-fMRI signal. Here, we develop a wavelet-based regularity analysis based on noise estimation capabilities of the wavelet transform to measure recurrent temporal pattern stability within the rs-fMRI signal across multiple temporal scales. The method consists of performing a stationary wavelet transform to preserve signal structure, followed by construction of "lagged" subsequences to adjust for correlated features, and finally the calculation of sample entropy across wavelet scales based on an "objective" estimate of noise level at each scale. We found that the brain's default mode network areas manifest a higher level of irregularity in rs-fMRI time series than rest of the brain. In 25 aged subjects with mild cognitive impairment and 25 matched healthy controls, wavelet-based regularity analysis showed improved sensitivity in detecting changes in the regularity of rs-fMRI signals between the two groups within the DMN and executive control networks, compared with standard multiscale entropy analysis. Wavelet-based regularity analysis based on noise estimation capabilities of the wavelet transform is a promising technique to characterize the dynamic structure of rs-fMRI as well as other biological signals.

Purpose To investigate the reliability and accuracy of two pseudo-continuous arterial spin labeling sequences, using two-dimensional gradient-echo echo planar imaging and 3D gradient and spin echo as the readout, respectively. Materials and Methods Each sequence was performed twice 4 weeks apart on six normal control subjects, six elderly subjects with mild cognitive impairment, and one participant with Alzheimer's disease. Eight of these subjects also underwent H 215O positron emission tomography scans on the same day or proximal to their second MRI scan. The longitudinal repeatability of EPI and GRASE pCASL were evaluated with the intraclass correlation coefficient and within-subject coefficient of variation. Results The ICCs of global perfusion measurements were 0.697 and 0.413 for GRASE and EPI based pCASL respectively. GRASE pCASL also demonstrated a higher longitudinal repeatability for regional perfusion measurements across 24 regions-of-interests compared with EPI pCASL. When compared with PET, EPI pCASL showed a higher degree of spatial correlation with PET than GRASE pCASL, although the difference was not statistically significant. Conclusion The 3D GRASE pCASL offers better repeatability than 2D EPI pCASL, thereby may provide a reliable imaging marker for the evaluation of disease progression and treatment effects in MCI and early AD subjects. © 2013 Wiley Periodicals, Inc.