Bayesian characterization of uncertainty in intra-subject non-rigid registration

In settings where high-level inferences are made based on registered image data, the registration uncertainty can contain important information. In this article, we propose a Bayesian non-rigid registration framework where conventional dissimilarity and regularization energies can be included in the likelihood and the prior distribution on deformations respectively through the use of Boltzmann’s distribution. The posterior distribution is characterized using Markov Chain Monte Carlo (MCMC) methods with the effect of the Boltzmann temperature hyper-parameters marginalized under broad uninformative hyper-prior distributions. The MCMC chain permits estimation of the most likely deformation as well as the associated uncertainty. On synthetic examples, we demonstrate the ability of the method to identify the maximum a posteriori estimate and the associated posterior uncertainty, and demonstrate that the posterior distribution can be non-Gaussian. Additionally, results from registering clinical data acquired during neurosurgery for resection of brain tumor are provided; we compare the method to single transformation results from a deterministic optimizer and introduce methods that summarize the high-dimensional uncertainty. At the site of resection, the registration uncertainty increases and the marginal distribution on deformations is shown to be multi-modal.     

Clinical stakeholders’ opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units: an international Delphi study

Introduction

Selective decontamination of the digestive tract (SDD) is a prophylactic antibiotic regimen that is not widely used in practice. We aimed to describe the opinions of key ‘stakeholders’ about the validity of the existing evidence base, likely consequences of implementation, relative importance of their opinions in influencing overall practice, likely barriers to implementation and perceptions of the requirement for further research to inform the decision about whether to embark on a further large randomised controlled trial.

Methods

This was a Delphi study informed by comprehensive framework of possible determinants of health professionals’ behaviour to study Critical Care practice in four countries. There were four key stakeholder participant groups including ICU physicians, pharmacists, clinical leads, and clinical microbiologists/ infectious disease physicians. Round one comprised participant interviews and Rounds two and three were online questionnaires using Delphi method.

Results

In this study, 141 participants were recruited of whom 82% were retained. Participants rated themselves as knowledgeable about SDD. Antibiotic resistance was identified as the most important issue. SDD was seen as a low clinical priority but few participants reported strong opposition. There was moderate agreement that research to date has not adequately addressed concerns about antibiotic resistance and lacks generalizability. Participants indicated equipoise with regard to benefits and harms of SDD, and indicated strong support for a further randomised trial.

Conclusions

Clinicians have clinical equipoise about the effectiveness of SDD. Future research requires longer follow up to assess antibiotic resistance as well as greater validity/generalizability to provide definitive answers on the effectiveness of decontamination and effects on antibiotic resistance. SDD was regarded as not being a high clinical priority, which may limit future trial participation. These results have identified that further large randomised controlled trial of SDD in critical care is both warranted and appropriate.     

Administering Ziconotide and Monitoring Patients Treated with Ziconotide: Expert Opinions

Some patients with chronic pain who are intolerant of or refractory to treatment with systemic analgesics may benefit from intrathecal therapy. Ziconotide is the first nonopioid analgesic approved by the United States Food and Drug Administration for intrathecal administration. Several randomized, double-blind, placebo-controlled clinical trials have demonstrated the efficacy and safety of ziconotide. However, the maximum recommended dosing and titration schedule provided in the prescribing information may be too aggressive for some patients, and experience has demonstrated that ziconotide is better tolerated with slower titration to a lower maximum dose. Efficacy can be assessed by an evaluation of changes in pain, functionality, and quality of life. Cognitive adverse events may be subtle; therefore, it is important that health care professionals not only monitor patients for signs and symptoms of cognitive adverse events, but also teach family members how to do the same. Careful patient assessment and monitoring can help optimize the potential benefit from treatment with ziconotide.     

‘Race’ and Prostate Cancer Mortality in Equal-access Healthcare Systems

Background

Reports suggest worse health-related outcomes among black (vs white) men diagnosed with prostate cancer, but appropriate cause–effect inferences are complicated by the relationship of race and other prognostic factors.

Methods

We searched the literature to find contemporary articles focusing on mortality among black and white men with prostate cancer in equal-access healthcare systems. We also directly assessed the association of race and prostate cancer mortality by conducting an observational cohort analysis of 1270 veterans diagnosed with prostate cancer and followed for 11 to 16 years at 9 medical centers within the Veterans Health Administration.

Results

Among 5 reports providing quantitative results for the association of race and mortality among men with prostate cancer in equal-access systems, outcomes were similar for black and white men. Race also was not a prognostic factor in the observational cohort analysis of US veterans, with an adjusted hazard ratio for black (vs white) men and prostate cancer mortality of 0.90 (95% confidence interval, 0.58-1.40; P = .65).

Conclusions

Mortality among black and white patients with prostate cancer is similar in equal-access healthcare systems. Studies that find racial differences in mortality (including cause-specific mortality) among men with prostate cancer may not account fully for socioeconomic and clinical factors.     

Development and Preliminary Validation of the Thought Control Questionnaire for Adolescents (TCQ-A)

The Thought Control Questionnaire (TCQ, Wells and Davies in Behav Res Therapy, 32, pp 871–878, 1994) measures individual differences in thought suppression strategies. This study describes the development and psychometric properties of an adolescent version of the questionnaire. Pilot studies were conducted to make some of the items more accessible to young people while still retaining the meaning of the original items. The adolescent version of the questionnaire and measures of emotional disorder were then administered to 589 school pupils aged 13–17 years. Confirmatory factor analysis yielded mixed results with only partial support for a five factor solution. Subsequently exploratory factor analysis did suggest a five factor structure that was the same as the original TCQ with the only difference being two fewer items. The five factors were distraction, social control, worry, punishment and reappraisal. The TCQ-A showed good internal consistency and evidence of stability over time. Scores on the worry and punishment subscales were positively correlated with measures of emotional symptoms. These data provided initial support for the psychometric properties of the TCQ-A and extend findings suggesting worry and punishment strategies are associated with psychological vulnerability.     

Influence of Adiposity on Insulin Resistance and Glycemia Markers Among U.K. Children of South Asian,Black African-Caribbean,and White European Origin: Child Heart and Health Study in England

OBJECTIVE

Ethnic differences in type 2 diabetes risk between South Asians and white Europeans originate before adult life and are not fully explained by higher adiposity levels in South Asians. Although metabolic sensitivity to adiposity may differ between ethnic groups, this has been little studied in childhood. We have therefore examined the associations among adiposity, insulin resistance, and glycemia markers in children of different ethnic origins.

RESEARCH DESIGN AND METHODS

Cross-sectional study of 4,633 9- to 10-year-old children (response rate 68%) predominantly of South Asian, black African-Caribbean, and white European origin (n = 1,266, 1,176, and 1,109, respectively) who had homeostasis model assessments of insulin resistance (HOMA-IR), glycemia markers (HbA_1c and fasting glucose), and adiposity (BMI, waist circumference, skinfold thicknesses, and bioimpedance [fat mass]).

RESULTS

All adiposity measures were positively associated with HOMA-IR in all ethnic groups, but associations were stronger among South Asians compared to black African-Caribbeans and white Europeans. For a 1-SD increase in fat mass percentage, percentage differences in HOMA-IR were 37.5% (95% CI 33.3–41.7), 29.7% (25.8–33.8), and 27.0% (22.9–31.2), respectively (P interaction < 0.001). All adiposity markers were positively associated with HbA_1c in South Asians and black African-Caribbeans but not in white Europeans; for a 1-SD increase in fat mass percentage, percentage differences in HbA_1c were 0.04% (95% CI 0.03–0.06), 0.04% (0.02–0.05), and 0.02% (−0.00 to 0.04), respectively (P interaction < 0.001). Patterns for fasting glucose were less consistent.

CONCLUSIONS

South Asian children are more metabolically sensitive to adiposity. Early prevention or treatment of childhood obesity may be critical for type 2 diabetes prevention, especially in South Asians.The prevalence of type 2 diabetes has been rising, both in the U.K. population (1) and worldwide (2,3). In the U.K., there are marked ethnic differences in the risks of type 2 diabetes, which are particularly high among South Asians and to a lesser extent black African-Caribbeans (4); increased type 2 diabetes risks are also apparent in these ethnic groups in the U.S. (5,6). Recent evidence suggests that ethnic differences in risks of type 2 diabetes are apparent in childhood, with higher levels of insulin resistance (a key precursor of type 2 diabetes), glycated hemoglobin (HbA_1c), and (less consistently) fasting blood glucose concentrations observed in U.K. South Asians and to a lesser extent black African-Caribbeans compared with white Europeans by the age of 10 years (7).Excess body fat (adiposity) is an important independent risk factor for the development of type 2 diabetes and insulin resistance both in adults (8,9) and children (10). However, the role of adiposity in these ethnic differences in type 2 diabetes is complex. In South Asian adults, it is well-recognized that BMI underestimates adiposity (11) and that body fat levels (particularly of central body fat) are higher than those of white Europeans (10,12–14). However, in most studies, adjusting for the higher body fat levels (usually assessed using skinfold thickness or waist and hip circumferences) has not accounted for the higher risks of diabetes and insulin resistance observed in South Asians (13,15–17). It has also been observed that the risks of diabetes, insulin resistance, and cardiovascular disease emerge at lower levels of adiposity (particularly BMI) in South Asian populations and that their associations with adiposity are stronger than those in white Europeans (13,17). We have previously shown in U.K. South Asian children that higher insulin and HbA_1c levels do not appear to be explained by higher adiposity levels (7,18). In a preliminary study, we also showed that insulin resistance in U.K. South Asian children may be more sensitive to adiposity than in white Europeans (18). However, this latter observation needs to be substantiated in larger scale studies in which insulin resistance, glycemia marker levels, and a range of adiposity markers are assessed in children from the relevant ethnic groups.We have therefore examined the cross-sectional associations among adiposity, insulin resistance, and glycemia markers in a study of ∼5,000 children of South Asian and white European origin aged 9 to 10 years; we also report on associations among children of black African-Caribbean origin. We hypothesized that metabolic sensitivity to adiposity would be greater in South Asians than white Europeans. Several adiposity markers were assessed, including measures based on skinfold thickness and bioimpedance, which provide robust measures of adiposity in this multiethnic population (19), as well as BMI and waist circumference. We have also included data on leptin, an adipokine with circulating levels that are strongly correlated with total body fat percentage (20). Because other studies have suggested that lower lean mass may be an important determinant of insulin resistance in young South Asian men (21), we also report on the influence of fat-free mass (FFM) on insulin resistance and glycemia.     

THE SPECIFICITY OF KERATINS

Kerateine and metakeratin were prepared from wool, chicken feathers and human hair. Chemical analyses revealed that the compounds are closely related. The results of serological studies disclose that species specificity is an individual characteristic of the keratins employed and that the specificity observed is dependent on the redox state of the sulfhydryl groupings in the protein molecule.