Residual doses in recent alluvial sediments from the ardenne (S Belgium)

peer reviewedWe report on our first investigations into the potential of optical dating for determining the rate of river flood sedimentation in the Ardenne region (S Belgium). Two samples collected from a recent alluvial deposit were used to investigate the extent of resetting in different particle size fractions of quartz (4-11 mu m, 63-90 mu m, 90-125 mu m, 125-180 mu m, 180-212 mu m and 212-250 mu m) as well as in polymineral fine (4-11 mu m) grains. Both samples show satisfactory OSL and IRSL characteristics. The IRSL signals from the polymineral fine grains yield an equivalent dose (D-e) of 3-4 Gy, while a D-e of 0.3-0.6 Gy was measured using large aliquots of quartz. Small aliquot analyses of 63-90 mu m and 212-250 mu m quartz grains confirm that the coarser fraction contains more grains with lower D-e's. Furthermore, for a modern sample (< 3 years old), similar to 60% of the aliquots yields a D-e consistent with zero, indicating that these contain only well-bleached grains. These findings suggest that it might be possible to extract the true burial dose from dose distributions measured using small aliquots of coarse-grained (e.g. 212-250 mu m) quartz

Assessment of aberrant DNA methylation two years after paediatric critical illness:a pre-planned secondary analysis of the international PEPaNIC trial

Critically ill children requiring intensive care suffer from impaired physical/neurocognitive development 2 y later, partially preventable by omitting early use of parenteral nutrition (early-PN) in the paediatric intensive-care-unit (PICU). Altered methylation of DNA from peripheral blood during PICU-stay provided a molecular basis hereof. Whether DNA-methylation of former PICU patients, assessed 2 y after critical illness, is different from that of healthy children remained unknown. In a pre-planned secondary analysis of the PEPaNIC-RCT (clinicaltrials.gov-NCT01536275) 2-year follow-up, we assessed buccal-mucosal DNA-methylation (Infinium-HumanMethylation-EPIC-BeadChip) of former PICU-patients (N = 406 early-PN; N = 414 late-PN) and matched healthy children (N = 392). CpG-sites differentially methylated between groups were identified with multivariable linear regression and differentially methylated DNA-regions via clustering of differentially methylated CpG-sites using kernel-estimates. Analyses were adjusted for technical variation and baseline risk factors, and corrected for multiple testing (false-discovery-rate <0.05). Differentially methylated genes were functionally annotated (KEGG-pathway database), and allocated to three classes depending on involvement in physical/neurocognitive development, critical illness and intensive medical care, or pre-PICU-admission disorders. As compared with matched healthy children, former PICU-patients showed significantly different DNA-methylation at 4047 CpG-sites (2186 genes) and 494 DNA-regions (468 genes), with most CpG-sites being hypomethylated (90.3%) and with an average absolute 2% effect-size, irrespective of timing of PN initiation. Of the differentially methylated KEGG-pathways, 41.2% were related to physical/neurocognitive development, 32.8% to critical illness and intensive medical care and 26.0% to pre-PICU-admission disorders. Two years after critical illness in children, buccal-mucosal DNA showed abnormal methylation of CpG-sites and DNA-regions located in pathways known to be important for physical/neurocognitive development

Managing the complexity of doing it all : an exploratory study on students' experiences when trained stepwise in conducting consultations

Background: At most medical schools the components required to conduct a consultation, medical knowledge, communication, clinical reasoning and physical examination skills, are trained separately. Afterwards, all the knowledge and skills students acquired must be integrated into complete consultations, an art that lies at the heart of the medical profession. Inevitably, students experience conducting consultations as complex and challenging. Literature emphasizes the importance of three didactic course principles: moving from partial tasks to whole task learning, diminishing supervisors' support and gradually increasing students' responsibility. This study explores students' experiences of an integrated consultation course using these three didactic principles to support them in this difficult task. Methods: Six focus groups were conducted with 20 pre-clerkship and 19 clerkship students in total. Discussions were audiotaped, transcribed and analysed by Nvivo using the constant comparative strategy within a thematic analysis. Results: Conducting complete consultations motivated students in their learning process as future physician. Initially, students were very much focused on medical problem solving. Completing the whole task of a consultation obligated them to transfer their theoretical medical knowledge into applicable clinical knowledge on the spot. Furthermore, diminishing the support of a supervisor triggered students to reflect on their own actions but contrasted with their increased appreciation of critical feedback. Increasing students' responsibility stimulated their active learning but made some students feel overloaded. These students were anxious to miss patient information or not being able to take the right decisions or to answer patients' questions, which sometimes resulted in evasive coping techniques, such as talking faster to prevent the patient asking questions. Conclusion: The complex task of conducting complete consultations should be implemented early within medical curricula because students need time to organize their medical knowledge into applicable clinical knowledge. An integrated consultation course should comprise a step-by-step teaching strategy with a variety of supervisors' feedback modi, adapted to students' competence. Finally, students should be guided in formulating achievable standards to prevent them from feeling overloaded in practicing complete consultations with simulated or real patients

The association of hypoglycemia with outcome of critically ill children in relation to nutritional and blood glucose control strategies

Abstract Background Withholding parenteral nutrition (PN) until one week after PICU admission facilitated recovery from critical illness and protected against emotional and behavioral problems 4 years later. However, the intervention increased the risk of hypoglycemia, which may have counteracted part of the benefit. Previously, hypoglycemia occurring under tight glucose control in critically ill children receiving early PN did not associate with long-term harm. We investigated whether hypoglycemia in PICU differentially associates with outcome in the context of withholding early PN, and whether any potential association with outcome may depend on the applied glucose control protocol. Methods In this secondary analysis of the multicenter PEPaNIC RCT, we studied whether hypoglycemia in PICU associated with mortality (N = 1440) and 4-years neurodevelopmental outcome (N = 674) through univariable comparison and multivariable regression analyses adjusting for potential confounders. In patients with available blood samples (N = 556), multivariable models were additionally adjusted for baseline serum NSE and S100B concentrations as biomarkers of neuronal, respectively, astrocytic damage. To study whether an association of hypoglycemia with outcome may be affected by the nutritional strategy or center-specific glucose control protocol, we further adjusted the models for the interaction between hypoglycemia and the randomized nutritional strategy, respectively, treatment center. In sensitivity analyses, we studied whether any association with outcome was different in patients with iatrogenic or spontaneous/recurrent hypoglycemia. Results Hypoglycemia univariably associated with higher mortality in PICU, at 90 days and 4 years after randomization, but not when adjusted for risk factors. After 4 years, critically ill children with hypoglycemia scored significantly worse for certain parent/caregiver-reported executive functions (working memory, planning and organization, metacognition) than patients without hypoglycemia, also when adjusted for risk factors including baseline NSE and S100B. Further adjustment for the interaction of hypoglycemia with the randomized intervention or treatment center revealed a potential interaction, whereby tight glucose control and withholding early PN may be protective. Impaired executive functions were most pronounced in patients with spontaneous or recurrent hypoglycemia. Conclusion Critically ill children exposed to hypoglycemia in PICU were at higher risk of impaired executive functions after 4 years, especially in cases of spontaneous/recurrent hypoglycemia

Solar Driven Photocatalytic Activity of Porphyrin Sensitized TiO2: Experimental and Computational Studies

The absence of a secure long-term sustainable energy supply is recognized as a major worldwide technological challenge. The generation of H2 through photocatalysis is an environmentally friendly alternative that can help solve the energy problem. Thus, the development of semiconductor materials that can absorb solar light is an attractive approach. TiO2 has a wide bandgap that suffers from no activity in the visible spectrum, limiting its use of solar radiation. In this research, the semiconductor absorption profile was extended into the visible region of the solar spectrum by preparing porphyrin-TiO2 (P-TiO2) composites of meso-tetra(4-bromophenyl)porphyrin (PP1) and meso-tetra(5-bromo-2-thienyl)porphyrin (PP2) and their In(III), Zn(II) and Ga(III) metal complexes. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were performed on the porphyrins to gain insight into their electron injection capability. The results demonstrate that P-TiO2 systems merit further in-depth study for applications that require efficient photocatalytic H2 generation

Leukocyte telomere length in paediatric critical illness

__Background:__ Children who have suffered from critical illnesses that required treatment in a paediatric intensive care unit (PICU) have long-term physical and neurodevelopmental impairments. The mechanisms underlying this legacy remain largely unknown. In patients suffering from chronic diseases hallmarked by inflammation and oxidative stress, poor long-term outcome has been associated with shorter telomeres. Shortened telomeres have also been reported to result from excessive food consumption and/or unhealthy nutrition. We investigated whether critically ill children admitted to the PICU have shorter-than-normal telomeres, and whether early parenteral nutrition (PN) independently affects telomere length when adjusting for known determinants of telomere length. __Methods:__ Telomere length was quantified in leukocyte DNA from 342 healthy children and from 1148 patients who had been enrolled in the multicenter, randomised controlled trial (RCT), PEPaNIC. These patients were randomly allocated to initiation of PN within 24 h (early PN) or to withholding PN for one week in PICU (late PN). The impact of early PN versus late PN on the change in telomere length from the first to last PICU-day was investigated with multivariable linear regression analyses. __Results:__ Leukocyte telomeres were 6% shorter than normal upon PICU admission (median 1.625 (IQR 1.446-1.825) telomere/single-copy-gene ratio (T/S) units vs. 1.727 (1.547-1.915) T/S-units in healthy children (P < 0.0001)). Adjusted for potential baseline determinants and leukocyte composition, early PN was associated with telomere shortening during PICU stay as compared with late PN (estimate early versus late PN -0.021 T/S-units, 95% CI -0.038; 0.004, P = 0.01). Other independent determinants of telomere length identified in this model were age, gender, baseline telomere length and fraction of neutrophils in the sample from which the DNA was extracted. Telomere shortening with early PN was independent of post-randomisation factors affected by early PN, including longer length of PICU stay, larger amounts of insulin and higher risk of infection. __Conclusions:__ Shorter than normal leukocyte telomeres are present in critically ill children admitted to the PICU. Early initiation of PN further shortened telomeres, an effect that was independent of other determinants. Whether such telomere-shortening predisposes to long-term consequences of paediatric critical illness should be further investigated in a prospective follow-up study

Development of a portfolio of learning for postgraduate family medicine training in South Africa: a Delphi study

<p>Abstract</p> <p>Background</p> <p>Within the 52 health districts in South Africa, the family physician is seen as the clinical leader within a multi-professional district health team. Family physicians must be competent to meet 90% of the health needs of the communities in their districts. The eight university departments of Family Medicine have identified five unit standards, broken down into 85 training outcomes, for postgraduate training. The family medicine registrar must prove at the end of training that all the required training outcomes have been attained. District health managers must be assured that the family physician is competent to deliver the expected service. The Colleges of Medicine of South Africa (CMSA) require a portfolio to be submitted as part of the uniform assessment of all registrars applying to write the national fellowship examinations. This study aimed to achieve a consensus on the contents and principles of the first national portfolio for use in family medicine training in South Africa.</p> <p>Methods</p> <p>A workshop held at the WONCA Africa Regional Conference in 2009 explored the purpose and broad contents of the portfolio. The 85 training outcomes, ideas from the WONCA workshop, the literature, and existing portfolios in the various universities were used to develop a questionnaire that was tested for content validity by a panel of 31 experts in family medicine in South Africa, via the Delphi technique in four rounds. Eighty five content items (national learning outcomes) and 27 principles were tested. Consensus was defined as 70% agreement. For those items that the panel thought should be included, they were also asked how to provide evidence for the specific item in the portfolio, and how to assess that evidence.</p> <p>Results</p> <p>Consensus was reached on 61 of the 85 national learning outcomes. The panel recommended that 50 be assessed by the portfolio and 11 should not be. No consensus could be reached on the remaining 24 outcomes and these were also omitted from the portfolio. The panel recommended that various types of evidence be included in the portfolio. The panel supported 26 of the 27 principles, but could not reach consensus on whether the portfolio should reflect on the relationship between the supervisor and registrar.</p> <p>Conclusion</p> <p>A portfolio was developed and distributed to the eight departments of Family Medicine in South Africa, and the CMSA, to be further tested in implementation.</p

Phenotypic and Functional Properties of Helios+ Regulatory T Cells

Helios, an Ikaros family transcription factor, is preferentially expressed at the mRNA and protein level in regulatory T cells. Helios expression previously appeared to be restricted to thymic-derived Treg. Consistent with recent data, we show here that Helios expression is inducible in vitro under certain conditions. To understand phenotypic and functional differences between Helios+ and Helios− Treg, we profiled cell-surface markers of FoxP3+ Treg using unmanipulated splenocytes. We found that CD103 and GITR are expressed at high levels on a subset of Helios+ Treg and that a Helios+ Treg population could be significantly enriched by FACS sorting using these two markers. Quantitative real-time PCR (qPCR) analysis revealed increased TGF-β message in Helios+ Treg, consistent with the possibility that this population possesses enhanced regulatory potential. In tumor-bearing mice, we found that Helios+ Treg were relatively over-represented in the tumor-mass, and BrdU studies showed that, in vivo, Helios+ Treg proliferated more than Helios− Treg. We hypothesized that Helios-enriched Treg might exert increased suppressive effects. Using in vitro suppression assays, we show that Treg function correlates with the absolute number of Helios+ cells in culture. Taken together, these data show that Helios+ Treg represent a functional subset with associated CD103 and GITR expression

The national portfolio for postgraduate family medicine training in South Africa : a descriptive study of acceptability, educational impact, and usefulness for assessment

Background: Since 2007 a portfolio of learning has become a requirement for assessment of postgraduate family medicine training by the Colleges of Medicine of South Africa. A uniform portfolio of learning has been developed and content validity established among the eight postgraduate programmes. The aim of this study was to investigate the portfolio's acceptability, educational impact, and perceived usefulness for assessment of competence. Methods: Two structured questionnaires of 35 closed and open-ended questions were delivered to 53 family physician supervisors and 48 registrars who had used the portfolio. Categorical and nominal/ordinal data were analysed using simple descriptive statistics. The open-ended questions were analysed with ATLAS.ti software. Results: Half of registrars did not find the portfolio clear, practical or feasible. Workshops on portfolio use, learning, and supervision were supported, and brief dedicated time daily for reflection and writing. Most supervisors felt the portfolio reflected an accurate picture of learning, but just over half of registrars agreed. While the portfolio helped with reflection on learning, participants were less convinced about how it helped them plan further learning. Supervisors graded most rotations, suggesting understanding the summative aspect, while only 61% of registrars reflected on rotations, suggesting the formative aspects are not yet optimally utilised. Poor feedback, the need for protected academic time, and pressure of service delivery impacting negatively on learning. Conclusion: This first introduction of a national portfolio for postgraduate training in family medicine in South Africa faces challenges similar to those in other countries. Acceptability of the portfolio relates to a clear purpose and guide, flexible format with tools available in the workplace, and appreciating the changing educational environment from university-based to national assessments. The role of the supervisor in direct observations of the registrar and dedicated educational meetings, giving feedback and support, cannot be overemphasized

Factors confounding the assessment of reflection: a critical review

BACKGROUND: Reflection on experience is an increasingly critical part of professional development and lifelong learning. There is, however, continuing uncertainty about how best to put principle into practice, particularly as regards assessment. This article explores those uncertainties in order to find practical ways of assessing reflection. DISCUSSION: We critically review four problems: 1. Inconsistent definitions of reflection; 2. Lack of standards to determine (in)adequate reflection; 3. Factors that complicate assessment; 4. Internal and external contextual factors affecting the assessment of reflection. SUMMARY: To address the problem of inconsistency, we identified processes that were common to a number of widely quoted theories and synthesised a model, which yielded six indicators that could be used in assessment instruments. We arrived at the conclusion that, until further progress has been made in defining standards, assessment must depend on developing and communicating local consensus between stakeholders (students, practitioners, teachers, supervisors, curriculum developers) about what is expected in exercises and formal tests. Major factors that complicate assessment are the subjective nature of reflection's content and the dependency on descriptions by persons being assessed about their reflection process, without any objective means of verification. To counter these validity threats, we suggest that assessment should focus on generic process skills rather than the subjective content of reflection and where possible to consider objective information about the triggering situation to verify described reflections. Finally, internal and external contextual factors such as motivation, instruction, character of assessment (formative or summative) and the ability of individual learning environments to stimulate reflection should be considered