Advanced microsamples: Current applications and considerations for mass spectrometry-based metabolic phenotyping pipelines

Microsamples are collections usually less than 50 µL, although all devices that we have captured as part of this review do not fit within this definition (as some can perform collections of up to 600 µL); however, they are considered microsamples that can be self-administered. These microsamples have been introduced in pre-clinical, clinical, and research settings to overcome obstacles in sampling via traditional venepuncture. However, venepuncture remains the sampling gold standard for the metabolic phenotyping of blood. This presents several challenges in metabolic phenotyping workflows: accessibility for individuals in rural and remote areas (due to the need for trained personnel), the unamenable nature to frequent sampling protocols in longitudinal research (for its invasive nature), and sample collection difficulty in the young and elderly. Furthermore, venous sample stability may be compromised when the temperate conditions necessary for cold-chain transport are beyond control. Alternatively, research utilising microsamples extends phenotyping possibilities to inborn errors of metabolism, therapeutic drug monitoring, nutrition, as well as sport and anti-doping. Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. Research into the metabolic phenotyping of microsamples is limited; however, with advances in commercially available microsampling devices, common barriers such as volumetric inaccuracies and the ‘haematocrit effect’ in dried blood spot microsampling can be overcome. In this review, we provide an overview of the common uses and workflows for microsampling in metabolic phenotyping research. We discuss the advancements in technologies, highlighting key considerations and remaining knowledge gaps for the employment of microsamples in metabolic phenotyping research. This review supports the translation of research from the ‘bench to the community’

Developing a community-based intervention to improve quality of life in people with colorectal cancer: a complex intervention development study

Objectives: To develop and pilot a theory and evidence-based intervention to improve quality of life (QoL) in people with colorectal cancer. Design: A complex intervention development study. Setting: North East Scotland and Glasgow. Participants: Semistructured interviews with people with colorectal cancer (n=28), cancer specialists (n=16) and primary care health professionals (n=14) and pilot testing with patients (n=12). Interventions: A single, 1 h nurse home visit 6–12 weeks after diagnosis, and telephone follow-up 1 week later (with a view to ongoing follow-up in future). Primary and secondary outcome measures: Qualitative assessment of intervention feasibility and acceptability. Results: Modifiable predictors of QoL identified previously were symptoms (fatigue, pain, diarrhoea, shortness of breath, insomnia, anorexia/cachexia, poor psychological well-being, sexual problems) and impaired activities. To modify these symptoms and activities, an intervention based on Control Theory was developed to help participants identify personally important symptoms and activities; set appropriate goals; use action planning to progress towards goals; self-monitor progress and identify (and tackle) barriers limiting progress. Interview responses were generally favourable and included recommendations about timing and style of delivery that were incorporated into the intervention. The pilot study demonstrated the feasibility of intervention delivery. Conclusions: Through multidisciplinary collaboration, a theory-based, acceptable and feasible intervention to improve QoL in colorectal cancer patients was developed, and can now be evaluated

Incremental and Predictive Validity of the Antisocial Process Screening Device in a Community Sample of Male and Female Ethnic Minority and Caucasian Youth

The Antisocial Process Screening Device (APSD) is a well-supported tool for assessing psychopathic features in youth. However, most research with the APSD has been derived from clinical and forensic samples comprised mainly of male Caucasian and African American adolescents. In this prospective study, the incremental and predictive validity of the self-report APSD for violent and non-violent offending was examined in an ethnically diverse community sample of male and female youth (N = 335) aged 12 to 14. High-school students from a moderate sized city in Western Canada completed the self-report APSD and then completed the Self-Report of Offending 6 months later. Receiver Operating Characteristics analysis indicated that APSD total and subscale scores were predictive of violent and non-violent offending at 6-month follow-up with moderate to large effect sizes. In addition, total scores on the APSD added incremental predictive utility above and beyond traditional criminogenic predictors of youth offending (i.e., prior offending, delinquent peer affiliation, poor school achievement, substance use, low parental monitoring). Although sex differences emerged in the predictive utility of the Impulsivity subscale of the APSD vis-à-vis violent offending, sex did not moderate the relationship between APSD total, Narcissism, or Callous/Unemotional scores and offending. In addition, the predictive utility of the APSD did not vary as a function of the youth’s ethnic background. These findings suggest that: (1) the self-report APSD may have utility for risk or threat assessment with normative school populations, (2) APSD findings from higher risk samples generalize to a lower risk sample of high-school youth, and (3) predictive utility of APSD total scores do not differ across male and female Caucasian and ethnic minority youth. &nbsp

Supersymmetric predictions for the inclusive b→sγb\to s\gamma decay

We study the penguin induced transition $b\to s\ \gamma$ in the minimal N=1 supersymmetric extension of the Standard Model with radiative breaking of the electroweak group. We include the effects of one-loop corrections to the Higgs potential and scalar masses. We show that the present upper and lower experimental limits on the inclusive decay sharply constrain the parameter space of the model in a wide range of $\tan\beta$ values. The implications of the recently advocated relation $|B|\ge 2$ for the bilinear SUSY soft breaking parameter in grand unified theories are also analyzed.Comment: 23 pages + 12 figures (hardcopies available on request), LATEX, SISSA 40/94/E

Flow cytometric analysis of the T cell response in mice infected with Cowdria ruminantium

A 3-fold increase in the numbers of Lyt-2⁺ T cells in the circulating blood of mice infected and reinfected with the Welgevonden stock of Cowdria ruminantium, as determined by flow cytometry, is supportive evidence that immunity in heartwater is cell-mediated. The rise in Lyt-2⁺ cells only after reinfection of the mice is further evidence that the development of immunity in heartwater is dependent on the unhindered and adequate replication of C. ruminantium.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.mn201

Routine thyroglobulin, neck ultrasound and physical examination in the routine follow up of patients with differentiated thyroid cancer—Where is the evidence?

Purpose: Patients with differentiated thyroid cancer (DTC) typically have a favourable prognosis and recurrence as late as 45 years after diagnosis has been reported. International clinical guidelines for monitoring recommend routine thyroglobulin, ultrasound and physical examination for the detection of recurrence. The aim of this review was to systematically review whether routine monitoring using thyroglobulin (Tg), neck ultrasound and physical examination for recurrence in differentiated thyroid cancer patients is effective in improving patient survival and/or quality of life. Methods: Primary studies were retrieved via a comprehensive search of three electronic bibliographic databases (PubMed, Web of Science Core Collection and Cochrane Library) without time restriction. Eligible studies must have reported on disease-free patients with DTC subject to long-term routine surveillance. The primary and secondary outcomes of interest were overall survival (or other survival parameters) and quality of life, respectively. Results: Literature searches yielded 5529 citations, which were screened by two reviewers. 241 full texts were retrieved. No randomised controlled trials or two-arm cohort studies on the effectiveness of any of the three specified interventions were identified. However, three ‘single-arm’ studies reporting long-term follow-up outcomes in patients undergoing regular surveillance were identified and appraised. Conclusions: This review highlights a lack of empirical evidence to support current use of routine surveillance in DTC. Although early detection is possible, routine surveillance may lead to unnecessary intervention

A low-voltage retarding-field Mott polarimeter for photocathode characterization

Nuclear physics experiments at Thomas Jefferson National Accelerator Facility's CEBAF rely on high polarization electron beams. We describe a recently commissioned system for prequalifying and studying photocathodes for CEBAF with a load-locked, low-voltage polarized electron source coupled to a compact retarding-field Mott polarimeter. The polarimeter uses simplified electrode structures and operates from 5 to 30 kV. The effective Sherman function for this device has been calibrated by comparison with the CEBAF 5 MeV Mott polarimeter. For elastic scattering from a thick gold target at 20 keV, the effective Sherman function is 0.201(5). Its maximum efficiency at 20 keV, defined as the detected count rate divided by the incident particle current, is 5.4(2) x 10-4, yielding a figure-of-merit, or analyzing power squared times efficiency, of 1.0(1) x 10-5. The operating parameters of this new polarimeter design are compared to previously published data for other compact Mott polarimeters of the retarding-field type.Comment: 9 figure

Multibeam Maser Survey of methanol and excited OH in the Magellanic clouds: new detections and maser abundance estimates

‘The definitive version is available at www.blackwell-synergy.com.’ Copyright Blackwell Publishing DOI: 10.1111/j.1365-2966.2008.12888.xPeer reviewe

Searching for chiral logs in the static-light decay constant

Using the clover fermion action in unquenched QCD with pion masses as low as 420 MeV, we look for evidence for chiral logs in the static-light decay constant. There is some evidence for a chiral log term, if the original static theory of Eichten and Hill is used. However, the more precise data from the static action of the ALPHA collaboration do not show any evidence for non-linear dependence of the static-light decay constant on the light quark mass. We make some comments on the connection between chiral perturbation theory for decay constants of the pion and static-light meson

Non-destructive, dynamic detectors for Bose-Einstein condensates

We propose and analyze a series of non-destructive, dynamic detectors for Bose-Einstein condensates based on photo-detectors operating at the shot noise limit. These detectors are compatible with real time feedback to the condensate. The signal to noise ratio of different detection schemes are compared subject to the constraint of minimal heating due to photon absorption and spontaneous emission. This constraint leads to different optimal operating points for interference-based schemes. We find the somewhat counter-intuitive result that without the presence of a cavity, interferometry causes as much destruction as absorption for optically thin clouds. For optically thick clouds, cavity-free interferometry is superior to absorption, but it still cannot be made arbitrarily non-destructive . We propose a cavity-based measurement of atomic density which can in principle be made arbitrarily non-destructive for a given signal to noise ratio