Hybridization and Selective Release of DNA Microarrays

DNA microarrays contain sequence specific probes arrayed in distinct spots numbering from 10,000 to over 1,000,000, depending on the platform. This tremendous degree of multiplexing gives microarrays great potential for environmental background sampling, broad-spectrum clinical monitoring, and continuous biological threat detection. In practice, their use in these applications is not common due to limited information content, long processing times, and high cost. The work focused on characterizing the phenomena of microarray hybridization and selective release that will allow these limitations to be addressed. This will revolutionize the ways that microarrays can be used for LLNL's Global Security missions. The goals of this project were two-fold: automated faster hybridizations and selective release of hybridized features. The first study area involves hybridization kinetics and mass-transfer effects. the standard hybridization protocol uses an overnight incubation to achieve the best possible signal for any sample type, as well as for convenience in manual processing. There is potential to significantly shorten this time based on better understanding and control of the rate-limiting processes and knowledge of the progress of the hybridization. In the hybridization work, a custom microarray flow cell was used to manipulate the chemical and thermal environment of the array and autonomously image the changes over time during hybridization. The second study area is selective release. Microarrays easily generate hybridization patterns and signatures, but there is still an unmet need for methodologies enabling rapid and selective analysis of these patterns and signatures. Detailed analysis of individual spots by subsequent sequencing could potentially yield significant information for rapidly mutating and emerging (or deliberately engineered) pathogens. In the selective release work, optical energy deposition with coherent light quickly provides the thermal energy to single spots to release hybridized DNA. This work leverages LLNL expertise in optics, microfluids, and bioinformatics

Walking the walk: a phenomenological study of long distance walking

Evidence suggests that regular walking can elicit significant psychological benefits although little evidence exists concerning long distance walking. The purpose of this study was to provide detailed accounts of the experiences of long distance walkers. Phenomenological interviews were conducted with six long distance walkers. Data were transcribed verbatim before researchers independently analyzed the transcripts. Participants reported a cumulative effect with positive feelings increasing throughout the duration of the walk. Long distance walking elicited positive emotions, reduced the effects of life-stress, and promoted an increased sense of well-being and personal growth. Results are aligned to theories and concepts from positive psychology

Evaluating the use of the Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) to estimate IQ in children with low intellectual ability

In situations where completing a full intellectual assessment is not possible or desirable the clinician or researcher may require an alternative means of accurately estimating intellectual functioning. There has been limited research in the use of proxy IQ measures in children with an intellectual disability or low IQ. The present study aimed to provide a means of converting total scores from a screening tool (the Child and Adolescent Intellectual Disability Screening Questionnaire: CAIDS-Q) to an estimated IQ. A series of linear regression analyses were conducted on data from 428 children and young people referred to clinical services, where FSIQ was predicted from CAIDS-Q total scores. Analyses were conducted for three age groups between ages 6 and 18 years. The study presents a conversion table for converting CAIDS-Q total scores to estimates of FSIQ, with corresponding 95% prediction intervals to allow the clinician or researcher to estimate FSIQ scores from CAIDS-Q total scores. It is emphasised that, while this conversion may offer a quick means of estimating intellectual functioning in children with a below average IQ, it should be used with caution, especially in children aged between 6 and 8 years old

Reporting randomised clinical trials of analgesics after traumatic or orthopaedic surgery is inadequate: a systematic review

Background Several randomised clinical trials (RCTs) of analgesics in postoperative pain after traumatic or orthopaedic surgery (TOS) have been published, but no studies have assessed the quality of these reports. We aimed to examine the quality of reporting RCTs on analgesics for postoperative pain after TOS. Methods Reports of RCTs assessing analgesics in postoperative pain after TOS were systematically searched from electronic databases. The quality of reports was assessed using the CONSORT checklist (scoring range from 0 to 22). The quality was considered poor when scoring was 12 or lesser. The publication year and the impact factor of journals were recorded. Results A total of 92 reports of RCTs were identified and 69 (75%) scored 12 or lesser in CONSORT checklist (range 5-17). The mean (SD) CONSORT score of all reports was 10.6 (2.7). Missing CONSORT items included primary and secondary outcome measures (11%), the specific objectives and hypothesis definition (12%), the sample size calculation (12%), the dates defining the periods of recruitment (12%), the discussion of external validity of findings (14%), the allocation sequence generation (24%), and the interpretation of potential bias or imprecision of results (25%). There was a little improvement in CONSORT scores over time (r = 0.62; p < 0.001) and with impact factor of journals (r = 0.30; p < 0.001). Conclusion Quality of reporting RCTs on analgesics after TOS is poor. Reporting of those RCTs should be improved according to methodological standard checklists in the next years

Time Resolved Phase Transitions via Dynamic Transmission Electron Microscopy

The Dynamic Transmission Electron Microscope (DTEM) project is developing an in situ electron microscope with nanometer- and nanosecond-scale resolution for the study of rapid laser-driven processes in materials. We report on the results obtained in a year-long LDRD-supported effort to develop DTEM techniques and results for phase transitions in molecular crystals, reactive multilayer foils, and melting and resolidification of bismuth. We report the first in situ TEM observation of the HMX {beta}-{delta} phase transformation in sub-{micro}m crystals, computational results suggesting the importance of voids and free surfaces in the HMX transformation kinetics, and the first electron diffraction patterns of intermediate states in fast multilayer foil reactions. This project developed techniques which are applicable to many materials systems and will continue to be employed within the larger DTEM effort

Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study.

OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results