Meeting Report: The Use of Newborn Blood Spots in Environmental Research: Opportunities and Challenges

IntroductionDried blood spots (DBS) are routinely collected from newborns in the United States using a heel stick. The DBS are screened for inborn errors of metabolism and other disorders. More states are keeping residual spots and making them available for research purposes. DNA extraction from the DBS has been widely applied; however, the development of methods to measure a range of environmental toxicants in DBS has been a more recent goal for laboratory scientists and epidemiologists.ObjectivesThe purpose of the meeting was to examine the utility of DBS to measure environmental exposures. Speakers and discussants were invited to present data and discuss approaches to measure a range of analytes using DBS.ResultsThis meeting was held on 20 February 2007 at the University of North Carolina at Chapel Hill. The audience consisted of epidemiologists, chemists, and staff from state public health programs, the Centers for Disease Control and Prevention, and the National Institutes of Health. The meeting included presentations on measurement of flame-retarding chemicals and pesticides, metals, perchlorate, infectious agents, markers of immune status, and protein adducts. Analytical methods included mass spectrometry, atomic absorption, molecular methods, and microfluidic techniques. Significant progress was reported, but important challenges remain. Concerns including storage conditions, sample volume, contamination, and normalization require additional systematic evaluation. In addition, DBS storage and access policies require coordination.ConclusionsDBS remain a highly valuable resource for clinical, epidemiologic, and toxicologic investigation. The use of DBS to measure environmental exposures shows promise but additional work is necessary before more widespread use is warranted

Chemical aspects related to using recycled geopolymers as aggregates

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Despite extensive research into sustainability of geopolymers, end-of-life aspects have been largely overlooked. A recycling scenario is examined in this study. This requires an investigation of alkali leaching potential from a geopolymeric matrix. To study the feasibility of geopolymer cement (GPC) recycling, the migration of alkalis was evaluated for the first time on a microstructural level through energy dispersive X-ray (EDX) scanning electron microscopy (SEM) elemental mapping and leaching tests. Macroscale impacts were assessed through an investigation of Portland cement (PC) mortar properties affected by alkali concentration. Leaching tests indicated that alkalis immediately become available in aqueous environments, but the majority remain chemically or physically bound in the matrix. This type of leaching accelerates the initial setting of PC paste. Elemental mapping and EDX/SEM analysis showed a complex paste-aggregate interfacial transition zone. Exchange of calcium and sodium, revealed by the maps, resulted in the migration of sodium into the PC paste and the formation of additional calcium-silicon-based phases in the geopolymeric matrix. Strength values of mortars with 25% and 50% recycled aggregates (RA) showed negligible differences compared with the reference sample. Screening tests indicated a low potential for GPC RA inducing alkali-silica reaction. Transport of GPC RA alkalis and the underlying mechanisms were observed. This transport phenomenon was found to have minor effects on the properties of the PC mortar, indicating that recycling of geopolymers is a viable reuse practice.Peer reviewedFinal Published versio

Coronary bypass grafting using crossclamp fibrillation does not result in reliable reperfusion of the myocardium when the crossclamp is intermittently released: a prospective cohort study

BACKGROUND: Cross-clamp fibrillation is a well established method of performing coronary grafting, but its clinical effect on the myocardium is unknown. We sought to measure these effects clinically using the Khuri Intramyocardial pH monitor. METHODS: 50 episodes of cross-clamping were recorded in 16 patients who underwent CABG with crossclamp-fibrillation. An Intramyocardial pH probe measured the level of acidosis in the anterior and posterior myocardium in real-time. The pH at the start and end of each period of cross-clamping was recorded. RESULTS: It became very apparent that the pH of some patients recovered quickly while others entirely failed to recover. Thus the patients were split into 2 groups according to whether the pH recovered to above 6.8 after the first crossclamp-release (N = 8 in each group). Initial pH was 7.133 (range 6.974–7.239). After the first period of crossclamping the pH dropped to 6.381 (range 6.034–6.684). The pH in recoverers prior to the second XC application was 6.990(range 6.808–7.222) compared to only 6.455 (range 6.200–6.737) in patient's whose myocardium did not recover (P < 0.0005). This finding was repeated after the second XC release (mean pH 7.005 vs 6.537) and the third (mean pH 6.736 vs 6.376). However prior to separation from bypass the pH was close to the initial pH in both groups (7.062 vs 7.038). CONCLUSION: Crossclamp fibrillation does not result in reliable reperfusion of the myocardium between periods of crossclamping

Fixation artefact in an intra-operative frozen section: a potential cause of misinterpretation

The intra-operative histological assessment of fresh tissue can provide valuable diagnostic information and guide surgical management, however, even a limited exposure to standard fixation agents can potentially compromise analysis. Defined handling strategies should exist to facilitate the receipt of all specimens, in their optimal state, by the laboratory

Novel statistical approaches for non-normal censored immunological data: analysis of cytokine and gene expression data

Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects. Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding. Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping. Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression. Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets

The specificity and patterns of staining in human cells and tissues of p16INK4a antibodies demonstrate variant antigen binding

The validity of the identification and classification of human cancer using antibodies to detect biomarker proteins depends upon antibody specificity. Antibodies that bind to the tumour-suppressor protein p16INK4a are widely used for cancer diagnosis and research. In this study we examined the specificity of four commercially available anti-p16INK4a antibodies in four immunological applications. The antibodies H-156 and JC8 detected the same 16 kDa protein in western blot and immunoprecipitation tests, whereas the antibody F-12 did not detect any protein in western blot analysis or capture a protein that could be recognised by the H-156 antibody. In immunocytochemistry tests, the antibodies JC8 and H-156 detected a predominately cytoplasmic localised antigen, whose signal was depleted in p16INK4a siRNA experiments. F-12, in contrast, detected a predominately nuclear located antigen and there was no noticeable reduction in this signal after siRNA knockdown. Furthermore in immunohistochemistry tests, F-12 generated a different pattern of staining compared to the JC8 and E6H4 antibodies. These results demonstrate that three out of four commercially available p16INK4a antibodies are specific to, and indicate a mainly cytoplasmic localisation for, the p16INK4a protein. The F-12 antibody, which has been widely used in previous studies, gave different results to the other antibodies and did not demonstrate specificity to human p16INK4a. This work emphasizes the importance of the validation of commercial antibodies, aside to the previously reported use, for the full verification of immunoreaction specificity

The Diabetes Manual trial protocol – a cluster randomized controlled trial of a self-management intervention for type 2 diabetes [ISRCTN06315411]

Background The Diabetes Manual is a type 2 diabetes self-management programme based upon the clinically effective 'Heart Manual'. The 12 week programme is a complex intervention theoretically underpinned by self-efficacy theory. It is a one to one intervention meeting United Kingdom requirements for structured diabetes-education and is delivered within routine primary care. Methods/design In a two-group cluster randomized controlled trial, GP practices are allocated by computer minimisation to an intervention group or a six-month deferred intervention group. We aim to recruit 250 participants from 50 practices across central England. Eligibility criteria are adults able to undertake the programme with type 2 diabetes, not taking insulin, with HbA1c over 8% (first 12 months) and following an agreed protocol change over 7% (months 13 to 18). Following randomisation, intervention nurses receive two-day training and delivered the Diabetes Manual programme to participants. Deferred intervention nurses receive the training following six-month follow-up. Primary outcome is HbA1c with total and HDL cholesterol; blood pressure, body mass index; self-efficacy and quality of life as additional outcomes. Primary analysis is between-group HbA1c differences at 6 months powered to give 80% power to detect a difference in HbA1c of 0.6%. A 12 month cohort analysis will assess maintenance of effect and assess relationship between self-efficacy and outcomes, and a qualitative study is running alongside. Discussion This trial incorporates educational and psychological diabetes interventions into a single programme and assesses both clinical and psychosocial outcomes. The trial will increase our understanding of intervention transferability between conditions, those diabetes related health behaviours that are more or less susceptible to change through efficacy enhancing mechanisms and how this impacts on clinical outcomes

A Simple Colorimetric Assay for Specific Detection of Glutathione-S Transferase Activity Associated with DDT Resistance in Mosquitoes

Aedes mosquitoes transmit many human viral pathogens including dengue, yellow fever and chikungunya. Most of these pathogens have no specific treatment or vaccine and hence their control is reliant on controlling the mosquito vectors, which usually involves the use of insecticides. In order to prevent the alarming prospect of mosquito control failure due to the rapid selection and spread of insecticide resistance in several mosquito populations worldwide, it is essential that effective resistance management strategies are implemented and adhered to. The development of simple diagnostic tests for the early identification and monitoring of resistance is an important prerequisite for this task. Here, we describe the development of a simple colorimetric test for the detection of GSTE2-2/DDTase-based resistance in individual mosquitoes. The novel assay combines the most desirable features of specificity and sensitivity with the low cost and ease of use required for a routine test in endemic countries. It can have direct application in routine vector monitoring as a resistance indicator and help improve the sustainability of insecticide based control strategies

Microscopic Realization of the Kerr/CFT Correspondence

Supersymmetric M/string compactifications to five dimensions contain BPS black string solutions with magnetic graviphoton charge P and near-horizon geometries which are quotients of AdS_3 x S^2. The holographic duals are typically known 2D CFTs with central charges c_L=c_R=6P^3 for large P. These same 5D compactifications also contain non-BPS but extreme Kerr-Newman black hole solutions with SU(2)_L spin J_L and electric graviphoton charge Q obeying Q^3 \leq J_L^2. It is shown that in the maximally charged limit Q^3 -> J_L^2, the near-horizon geometry coincides precisely with the right-moving temperature T_R=0 limit of the black string with magnetic charge P=J_L^{1/3}. The known dual of the latter is identified as the c_L=c_R=6J_L CFT predicted by the Kerr/CFT correspondence. Moreover, at linear order away from maximality, one finds a T_R \neq 0 quotient of the AdS_3 factor of the black string solution and the associated thermal CFT entropy reproduces the linearly sub-maximal Kerr-Newman entropy. Beyond linear order, for general Q^3<J_L^2, one has a finite-temperature quotient of a warped deformation of the magnetic string geometry. The corresponding dual deformation of the magnetic string CFT potentially supplies, for the general case, the c_L=c_R=6J_L CFT predicted by Kerr/CFT.Comment: 18 pages, no figure

Diffusion of e-health innovations in 'post-conflict' settings: a qualitative study on the personal experiences of health workers.

BACKGROUND: Technological innovations have the potential to strengthen human resources for health and improve access and quality of care in challenging 'post-conflict' contexts. However, analyses on the adoption of technology for health (that is, 'e-health') and whether and how e-health can strengthen a health workforce in these settings have been limited so far. This study explores the personal experiences of health workers using e-health innovations in selected post-conflict situations. METHODS: This study had a cross-sectional qualitative design. Telephone interviews were conducted with 12 health workers, from a variety of cadres and stages in their careers, from four post-conflict settings (Liberia, West Bank and Gaza, Sierra Leone and Somaliland) in 2012. Everett Roger's diffusion of innovation-decision model (that is, knowledge, persuasion, decision, implementation, contemplation) guided the thematic analysis. RESULTS: All health workers interviewed held positive perceptions of e-health, related to their beliefs that e-health can help them to access information and communicate with other health workers. However, understanding of the scope of e-health was generally limited, and often based on innovations that health workers have been introduced through by their international partners. Health workers reported a range of engagement with e-health innovations, mostly for communication (for example, email) and educational purposes (for example, online learning platforms). Poor, unreliable and unaffordable Internet was a commonly mentioned barrier to e-health use. Scaling-up existing e-health partnerships and innovations were suggested starting points to increase e-health innovation dissemination. CONCLUSIONS: Results from this study showed ICT based e-health innovations can relieve information and communication needs of health workers in post-conflict settings. However, more efforts and investments, preferably driven by healthcare workers within the post-conflict context, are needed to make e-health more widespread and sustainable. Increased awareness is necessary among health professionals, even among current e-health users, and physical and financial access barriers need to be addressed. Future e-health initiatives are likely to increase their impact if based on perceived health information needs of intended users