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Background and study aim: Local resection of early rectal cancer is being increasingly used. With invasion of the muscularis propria layer of the rectal wall, the risk of lymph node metastasis becomes too high to consider this the optimal oncological treatment. Therefore, a diagnosis of muscular invasion is important before attempting local resection; however, endoscopic and magnetic resonance imaging (MRI) images have limitations, such as overstaging (26–31%). We investigated the potential of linear endoscopic ultrasound (L-EUS) in the diagnosis of muscularis propria invasion. Patients and methods: The study consisted of a development phase, in which linear (L)- EUS features, associated with muscular wall invasion were searched and tested, and a validation phase, during which 30 representative videos were assessed by the author F.t.B. and four experienced endosonographists without experience in rectal L-EUS. Results: The development cohort consisted of 91 patients (2019–2023). Overall, six EUS features were found to be significantly associated with muscular wall invasion: tornado sign, blob sign, massive connection, layer split, extramural deposit, and, most importantly impaired shiftability between the lesion and muscularis propria layer. During the development phase, these findings demonstrated excellent diagnostic features (sensitivity, 94.4%; specificity, 97.9%; and overstaging, 4%). In the validation phase, the sensitivity, specificity, and overstaging by F.t.B. were 88%, 85%, and 12%, respectively. Among the four inexperienced reviewers, the percentages were 65%–71%, 46%–54%, and 33%–39%, respectively. When considering the 27 videos that were considered easy or moderately difficult to assess, only 55% were correctly interpreted by the inexperienced reviewers. Conclusions: Linear endoscopic ultrasonography may be a valuable tool for the assessment of ingrowth into the muscularis propria in supposedly early rectal cancer, especially using its dynamic potential to assess fixation to the muscular wall by moving the lesion. However, training will be required to achieve satisfactory results. [ABSTRACT FROM AUTHOR]

Background: Although principles of the health promoting school (HPS) approach are followed worldwide, differences between countries in the implementation are reported. The aim of the current study was (1) to examine the implementation of the HPS approach in European countries in terms of different implementation indicators, that is, percentage of schools implementing the HPS approach, implementation of core components, and positioning on so‐called HPS‐related spectra, (2) to explore patterns of consistency between the implementation indicators across countries, and (3) to examine perceived barriers and facilitators to the implementation of the HPS approach across countries. Methods: This study analyzed data from a survey that was part of the Schools for Health in Europe network's Monitoring Task 2020. The survey was completed by HPS representatives of 24 network member countries. Results: Large variations exist in (the influencing factors for) the implementation of the HPS approach in European countries. Observed patterns show that countries with higher percentages of schools implementing the HPS approach also score higher on the implementation of the core components and, in terms of spectra, more toward implementing multiple HPS core components, add‐in strategies, action‐oriented research and national‐level driven dissemination. In each country a unique mix of barriers and facilitators was observed. Conclusion: Countries committed to implementing the HPS approach in as many schools as possible also seem to pay attention to the quality of implementation. For a complete and accurate measurement of implementation, the use of multiple implementation indicators is desirable. [ABSTRACT FROM AUTHOR]

This article analyzes ethical issues arising in transreligious foster care placements in relation to foster children's needs regarding religious socialization and identification. Applying Urban Walker's expressive-collaborative framework to 30 qualitative interviews with foster parents, foster children, parents, and professionals, we elaborate and apply a three-level reflection on Christian foster parents' ethics of care in everyday practice of foster care. A first-level reflection demonstrates that integrating the foster child in the foster family often leads to predominant Christian socialization of foster children. A second-level reflection demonstrates asymmetry between foster parents and birth parents in the religious socialization of foster children, leading to confusion for the foster child and (potential) conflict with birth parents. Finally, a normative reflection leads us to conclude that foster children in transreligious placements need loose and hybrid moral frames in which they can alter, shift, and navigate their multiple identifications and partialities as part of their development. [ABSTRACT FROM AUTHOR]

Background: School-based health-promoting interventions are increasingly seen as an effective population strategy to improve health and prevent obesity. Evidence on the long-term effectiveness of school-based interventions is scarce. This study investigates the four-year effectiveness of the school-based Healthy Primary School of the Future (HPSF) intervention on children's body mass index z-score (BMIz), and on the secondary outcomes waist circumference (WC), dietary and physical activity (PA) behaviours. Methods and findings: This study has a quasi-experimental design with four intervention schools, i.e., two full HPSFs (focus: diet and PA), two partial HPSFs (focus: PA), and four control schools. Primary school children (aged 4–12 years) attending the eight participating schools were invited to enrol in the study between 2015 and 2019. Annual measurements consisted of children's anthropometry (weight, height and waist circumference), dietary behaviours (child- and parent-reported questionnaires) and PA levels (accelerometers). Between 2015 and 2019, 2236 children enrolled. The average exposure to the school condition was 2·66 (SD 1·33) years, and 900 participants were exposed for the full four years (40·3%). After four years of intervention, both full (estimated intervention effect (B = -0·17 (95%CI -0·27 to -0·08) p = 0·000) and partial HPSF (B = -0·16 (95%CI-0·25 to -0·06) p = 0·001) resulted in significant changes in children's BMIz compared to control schools. Likewise, WC changed in favour of both full and partial HPSFs. In full HPSFs, almost all dietary behaviours changed significantly in the short term. In the long term, only consumption of water and dairy remained significant compared to control schools. In both partial and full HPSFs, changes in PA behaviours were mostly absent. Interpretation: This school-based health-promoting intervention is effective in bringing unfavourable changes in body composition to a halt in both the short and long term. It provides policy makers with robust evidence to sustainably implement these interventions in school-based routine. [ABSTRACT FROM AUTHOR]

Introduction: Epidermal growth factor receptor (EGFR) mutated NSCLC is best treated using an EGFR tyrosine kinase inhibitor (TKI). The presence and accessibility of EGFR overexpression and mutation in NSCLC can be determined using radiolabeled EGFR TKI PET/CT. However, recent research has shown a significant difference between image qualities (i.e., tumor-to-lung contrast) in three generation EGFR TKIs: 11C-erlotinib, 18F-afatinib and 11C-osimertinib. In this research we aim to develop a physiological pharmacokinetic (PBPK)-model to predict tumor-to-lung contrast and as a secondary outcome the uptake of healthy tissue of the three tracers. Methods: Relevant physicochemical and drug specific properties (e.g., pKa, lipophilicity, target binding) for each TKI were collected and applied in established base PBPK models. Key hallmarks of NSCLC include: immune tumor deprivation, unaltered tumor perfusion and an acidic tumor environment. Model accuracy was demonstrated by calculating the prediction error (PE) between predicted tissue-to-blood ratios (TBR) and measured PET-image-derived TBR. Sensitivity analysis was performed by excluding each key component and comparing the PE with the final mechanistical PBPK model predictions. Results: The developed PBPK models were able to predict tumor-to-lung contrast for all EGFR-TKIs within threefold of observed PET image ratios (PE tumor-to-lung ratio of −90%, +44% and −6.3% for erlotinib, afatinib and osimertinib, respectively). Furthermore, the models depicted agreeable whole-body distribution, showing high tissue distribution for osimertinib and afatinib and low tissue distribution at high blood concentrations for erlotinib (mean PE, of −10.5%, range −158%–+190%, for all tissues). Conclusion: The developed PBPK models adequately predicted the image quality of afatinib and osimertinib and erlotinib. Some deviations in predicted whole-body TBR lead to new hypotheses, such as increased affinity for mutated EGFR and active influx transport (erlotinib into excreting tissues) or active efflux (afatinib from brain), which is currently unaccounted for. In the future, PBPK models may be used to predict the image quality of new tracers. [ABSTRACT FROM AUTHOR]

This case study demonstrates how animal abuse investigations can benefit from collaboration between forensic anthropologists and veterinary pathologists, especially in investigations involving trauma assessment of skeletal remains. In 2009, four deceased dogs were excavated from a residential property in conjunction with a case of suspected animal abuse. The decomposed remains were skeletonized to permit assessment of biological profiles, individualization, and trauma analysis. Each dog was identified based on their sex, age‐at‐death, fur coloration patterns, and through investigative information. The analysis conducted by forensic anthropologists in collaboration with a veterinary pathologist revealed evidence of perimortem blunt force trauma on all four skeletons. The distribution and severity of the injuries, including fractures concentrated mainly on the axial skeleton (i.e., skull, thorax, and vertebral column) and pelvis, are consistent with documented cases of non‐accidental injury (NAI) reported in the literature. Healed rib fractures were also noted on one of the dogs, and likely occurred a few weeks prior to death, further supporting a diagnosis of NAI. The skeletal trauma findings were inconsistent with the dog owner's account of how each dog had died and were instrumental in resolving the investigation. [ABSTRACT FROM AUTHOR]

Strontium and oxygen isotope values are used in conjunction with a maximum likelihood assignment model to predict the childhood and adulthood geographic residences of 20 deceased migrants recovered along the México-U.S. border in south Texas. The objectives of this research are to determine (1) if the childhood and adulthood residency assignments predict the same geographic region, (2) if using the predicted residential history/nationality as a filter on the National Missing and Unidentified Persons System (NamUs) reduces the number of potential matching missing person reports, and (3) if we should target teeth or bone as the optimal hard tissue to sample. We found that 12 of the 20 cases (60%) predict similar regions of residency using isotopes derived from bone bioapatite (adulthood residency) and tooth bioapatite (childhood residency). When predicted residential history/nationality data were used as a filter in NamUs, there was a significant reduction in the mean number of case searches (mean = 1568.5 ± 505.3 [1 SD] vs. 107.9 ± 142.6 [1 SD]; t = 12.441, df= 22, p < 0.001, unequal variances assumed). These results demonstrate the utility of isotope data for narrowing down the region of origin and in turn the number of missing persons records to review. Finally, we recommend that death investigators at minimum collect dental samples (premolars or molars) for future unidentified migrant cases to aid in identification efforts utilizing isotope analytical methods. Bone bioapatite samples can provide more recent residential history information but should be used in conjunction with tooth enamel data. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether published pharmacokinetic (PK) models can adequately predict the PK profile of imatinib in a new indication, such as coronavirus disease 2019 (COVID‐19). Total (bound + unbound) and unbound imatinib plasma concentrations obtained from 134 patients with COVID‐19 participating in the CounterCovid study and from an historical dataset of 20 patients with gastrointestinal stromal tumor (GIST) and 85 patients with chronic myeloid leukemia (CML) were compared. Total imatinib area under the concentration time curve (AUC), maximum concentration (Cmax) and trough concentration (Ctrough) were 2.32‐fold (95% confidence interval [CI] 1.34–3.29), 2.31‐fold (95% CI 1.33–3.29), and 2.32‐fold (95% CI 1.11–3.53) lower, respectively, for patients with CML/GIST compared with patients with COVID‐19, whereas unbound concentrations were comparable among groups. Inclusion of alpha1‐acid glycoprotein (AAG) concentrations measured in patients with COVID‐19 into a previously published model developed to predict free imatinib concentrations in patients with GIST using total imatinib and plasma AAG concentration measurements (AAG‐PK‐Model) gave an estimated mean (SD) prediction error (PE) of −20% (31%) for total and −7.0% (56%) for unbound concentrations. Further covariate modeling with this combined dataset showed that in addition to AAG; age, bodyweight, albumin, CRP, and intensive care unit admission were predictive of total imatinib oral clearance. In conclusion, high total and unaltered unbound concentrations of imatinib in COVID‐19 compared to CML/GIST were a result of variability in acute phase proteins. This is a textbook example of how failure to take into account differences in plasma protein binding and the unbound fraction when interpreting PK of highly protein bound drugs, such as imatinib, could lead to selection of a dose with suboptimal efficacy in patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Letter to the Editor - Moving beyond a lost cause: Forensic anthropology and ancestry estimates in the United States. Bethard and DiGangi opened a dialogue on the application of ancestry estimation as part of the biological profile in forensic anthropology [1]. Anthropologists accept the social construction of race and are acutely aware of its harmful impact in American society, particularly with respect to the historic use of anthropology to promote scientific racism. Research has assessed accuracy rates of ancestry estimations by forensic anthropologists and reported correct ancestry estimates at 90.9% [13]. [Extracted from the article]

In this essay, I explore Pentecostal approaches to governance and security, taking an anthropological approach. I focus on Pentecostalism as a distinctive way of looking at and being in the world, one that understands the family as central in its approach governance and security. I highlight the paradox between Pentecostalism's strong orientation towards individual and family moral conduct and practices of female leadership in Pentecostal contexts. I conclude with some broader reflections on the implications for diplomacy and other practitioners of foreign policy. [ABSTRACT FROM AUTHOR]

One of the many difficulties associated with identifying undocumented border crossers stems from an inability to narrow down the search area for the region of origin and family members to obtain family reference samples for DNA comparison. While the geography of regions of origins is wide, the biological profiles of the undocumented border crossers often show strong similarities, young and male. The isotopic composition of human bones, teeth, and hair has been demonstrated to be useful biomarkers for tracing locations and movements of individuals and for aiding in the identification of human remains. Data obtained from human remains can be compared to and aligned with various reference sources, such as soils and bedrock, archaeological remains, or cultural data. Here, the spatial deficiency in isotopic reference data for Mexico, specifically for oxygen (δ18O) isotopes in tap water, is being addressed through the collection and analysis of over 150 water samples and explored with tooth enamel isotopic values from recently identified Mexican nationals. The isoscape was developed using a Spine with Barriers interpolation method and shows sufficient detail to narrow down the regions where specific isotopic values are represented. The individuals were plotted on the developed isoscape using conditional correlations. The methodology was successful in assigning the correct regions of origin for the two individuals, which shows the tremendous potential of the developed isoscape. Nonetheless, there is more research needed to further improve upon this geolocation method, including analysis of multiple isotopes in different tissues, and the development of new isotopic methods. [ABSTRACT FROM AUTHOR]

Aim: The aim of this systematic review is to obtain a better understanding of the association between unemployment among young people and mental health. Methods : After screening the title and abstract of 794 articles drawn from four electronic databases, 52 articles remained for full-text reading. Of these, 20 studies met the inclusion criteria and were assessed on methodological quality. All steps were performed independently by two reviewers. Finally, a total of 17 articles were included in the systematic review. Results : Analysis of cross-sectional studies (N = 5) showed an association between unemployment among young people and mental health. An effect of unemployment on mental health was found when considering cohort studies (N = 12) that did not control for confounders (7/7). When controlling for confounders except mental health at baseline, this effect decreased in most studies leading to mixed results, although the majority (6/8) still found an effect. However, when taking mental health at baseline into account as one of the confounders, only a minority of studies (3/8) found a significant effect of unemployment on mental health. Conclusions : This systematic review showed an association between unemployment among young people and mental health. However, whether there is a causal relationship is less clear. More evidence from, for example, natural experiments and longitudinal studies that control for confounding variables, especially mental health at baseline, is required to better understand the association and potential causation between unemployment among young people and mental health. [ABSTRACT FROM AUTHOR]

Certification through the American Board of Forensic Anthropology (ABFA) provides forensic anthropologists with accredited validation of the highest level of qualifications (including education and training) and professionalism in the discipline, through rigorous vetting of an applicant's casework, knowledge, and skill. It encourages adherence to best practice methodological and ethical standards and provides a system of recognition of qualified professionals to external agencies. Current policies and procedures (and their evolution) for ABFA certification are reviewed as they contribute to construction of an equitable, impartial, and objective system for assessing and endorsing professional competency. Advice is provided for ABFA applicants for successful navigation of the ABFA certification process. [ABSTRACT FROM AUTHOR]

The professionalization of forensic anthropology in North America began with the establishment of the Physical Anthropology section (now Anthropology Section) of the American Academy of Forensic Sciences (AAFS) in 1972 and the development of the American Board of Forensic Anthropology (ABFA) board certification program in 1977-78. This review first outlines the history of ABFA board certification, then discusses temporal trends among ABFA diplomate recipients, ABFA leadership, and ABFA qualification requirements (i.e., examination structure and content). The data reveal that ABFA demographic and qualification developments mirror academic trends in the discipline over the past four decades. Our assessment indicates substantial growth of the ABFA from the year 2000 to present, a shorter waiting period between receipt of the PhD and board certification, and a significant shift toward a membership and leadership reflective of a younger cohort with greater representation by women. Changes in ABFA qualifications, as revealed by an exam content review over this period, reflect many of the academic trends we have seen in our discipline as a whole, including greater specialization, reliance on technological advancements, recognition of population variability, and the need to accurately measure and mitigate error and bias. With the increased availability of DNA analysis, biological profile research and expertise may be giving way to other specializations within forensic anthropology, including bone morphology, skeletal growth and development, fracture biomechanics, fracture healing, and taphonomy, including time since death estimation. [ABSTRACT FROM AUTHOR]

This article analyses how faith-based civil society organisations have advocated the value-add of faith to governmental and non-governmental development actors in the highly secularised context of the Netherlands. Its social value lies in the space for reflexivity it opens up on how the religious and the secular are entangled in the field of development through shifting the gaze towards secularised Europe. Its academic value lies in how it combines the study of faith and development, with a critical analysis of the secular formations in which much of the thinking around faith and development is shaped. The article builds on an academic study of and long-term engagement with the Dutch non-governmental organisation (NGO)-based Knowledge Centre Religion and Development (KCRD), offering a critical overview of the KCRD's work between 2006 and 2016. Data were gathered through interviews, document analysis and participant observation as part of the academic research, as well as informal observations and analysis through professional engagement. The KCRD, because of its institutional setting, had to adopt an instrumental approach towards the role of religion in development, which prevented it from challenging the reigning secular paradigm in development and its biases towards faith-based actors. The article will recommend that future initiatives on faith and development more consciously anchor their approach to faith in their institutional practices and mainstream discussions on the European continent. [ABSTRACT FROM AUTHOR]

Bioarchaeological studies of dental caries have found that females often exhibit a higher prevalence of dental caries than their male counterparts. While this trend is most often noted in prehistoric agricultural populations, recent research has also indicated a higher prevalence of dental caries among prehistoric female hunter-gatherers from California's Central Valley Windmiller culture (4500–2500 BP) compared to their male counterparts. This study expands on this earlier research to include additional Windmiller culture sites to test the hypothesis that females display greater caries prevalence than males. The prevalence of dental caries was assessed utilizing the dentitions of male and female individuals at four archeological sites in the California Central Valley: CA-SAC-107, CA-SJO-142, CA-SJO-56, and CA-SJO-68. A 'caries correction' factor was applied to account for antemortem tooth loss (ATML) from attrition versus AMTL due to caries. The results indicate that while females in all of the Central Valley populations analyzed display a greater proportion of dental caries than males, the difference is only statistically significant at CA-SJO-56 and CA-SJO-68. The prevalence rates at CA-SAC-107 approach significance, but are likely not significant due to sample size, while the lack of significance at CA-SJO-142 may be due to extremely high rates of dental attrition. While physiological differences likely contributed to the disparity in dental caries prevalence, these results suggest that differential access to resources, resulting from the sexual division of labor, also contributed to the higher rate of dental caries among females at these Windmiller sites. [ABSTRACT FROM AUTHOR]

We test the antiquity of a dietary life history model on Tutuila, American Samoa. Stable carbon and nitrogen isotopes in serial, age-adjusted samples of first and third molars reveal isotopic biographies of 16 individuals from five late Holocene (200-1100 RCYBP) sites. Combining this with bone collagen from a larger sample of individuals, we document a patterned dietary life history on the island. Between ages zero and two years, infants show elevated δ15N values, consistent with a diet rich in breast milk. In early childhood (two-10 years), individuals shift to a diet with higher δ13C values, suggesting greater marine protein intake. Around age 10 years, males shift to a more terrestrially focused diet, while females retain a higher marine signature. After ~20 years of age, males and females are more similar in diet, with a greater contribution from terrestrial resources. We argue that these shifts reflect diet-marked social transitions in life histories, especially social status and eating order within households, as predicted from the ethnographic model. When contextualized with other archaeological data, such as mortuary patterns and social organization, the isotopic biographic approach facilitates examination of diet-linked social transitions of individuals as they aged within ancient societies. [ABSTRACT FROM AUTHOR]

Background: Clinician-scientists (CSs) are physicians who work in daily care and have an academic role in research or education. They may act as knowledge brokers and help to connect research and clinical practice. There is no data available on CSs' brokering activities and the perceived barriers and facilitators to optimising their role in general practice (GP) and elderly care medicine (EM). Aim: To identify the brokering activities of CSs in these fields and the barriers and facilitators they come across whilst sharing knowledge and connecting people in research and frontline health care. Design and setting: Qualitative interview study among 17 Dutch senior CSs. Method: Interview data were audio recorded, transcribed verbatim and thematic interpretative analysis was used to identify themes. Results: CSs facilitate collaboration between researchers and practitioners. They exchange knowledge on both sides, make use of extensive networks and constantly and actively involve care in research and research in care. CSs come across barriers as well as facilitators that influence their brokering activities. Some barriers and facilitators are at the individual level, other are related more to the job context and workplace. Conclusions: This study reveals barriers to overcome and facilitators to develop related to the brokering role of CSs. To make the best use of CSs, brokering activities and the added value of CSs should be recognised and supported. Awareness of what CSs need to function effectively in demanding work settings could be important for the future impact of the role on the fields of GP and EM. [ABSTRACT FROM AUTHOR]

Variation in human breastfeeding and weaning practices is subject to changing social pressures and norms, as well as individual agency. This paper presents a case study from the Yukisma Mound (CA‐SCL‐38), a prehistoric site in the San Francisco Bay Area, which was used as a ceremonial and cemetery space by the ancestral Ohlone Indians between 780 and 230 cal years bp. Stable carbon and nitrogen isotope values from bone collagen of 201 individuals, including 26 subadults, are analysed. The Weaning Age Reconstruction with Nitrogen isotope analysis package in R is used to model expected δ15N values of infant bone collagen, against which measured δ15N values reveal individual variation in weaning practices. Infants from this burial sample were exclusively breastfed until approximately 0.8 years (maximum density estimation (MDE), marginal probability = 0.0456), and completely weaned by around 4.4 years (MDE, marginal probability =.0409). Range of variation in adult diets is used as a baseline of comparison, in addition to mean δ15N values of adult females, to better consider supplementary food options, and to avoid the assumption of a homogeneous maternal diet. Comparison with weaning data from contemporaneous regional sites, drawn from studies using tooth dentin of individuals who survived childhood, reveals that introduction of complementary foods and cessation of breastfeeding occurred somewhat later at the Yukisma Mound. This contrast suggests prolonged supplementation with breastmilk for children who expressed nutritional stress or disease. Variation in weaning trajectories is further interpreted using δ13C values to identify individuals with elevated δ15N values due to supplementation with high trophic level foods (e.g., freshwater fish and marine foods). Changes in weaning practices are demonstrated by comparison of this sample to ethnohistoric accounts of the Ohlone. This study provides an example of collaborative research with descendent populations and of making the most of available materials. [ABSTRACT FROM AUTHOR]

Background: RealFit is a 13-week weight-reduction programme for adolescents. This study investigated the programme’s long-term effectiveness regarding the psychological outcomes of self-esteem and food craving.Methods: The study had a quasi-experimental design. Body mass index, self-esteem and food craving were assessed at baseline (T0), immediately after RealFit (T1), and after five months (T2) and one year (T3) of follow-up. Control participants (n = 32) were overweight adolescents who received no treatment.Results: Comparison between the intervention (n = 86) and control groups showed a significant difference for the self-esteem domain of global self-worth (1.63; 95% confidence interval: 0.28 to 2.99) in favour of the intervention group. The differences regarding overall self-esteem and the physical appearance domain showed a trend towards improvement. No significant difference was found for food craving.Conclusions: Taking all results and limitations into account, it may cautiously be concluded that RealFit has beneficial long-term effects on some domains of self-esteem, but no substantial effect on food craving. The appropriate duration and delivery of cue-exposure sessions in groups of overweight adolescents to decrease food craving should be investigated to further improve the RealFit intervention. [ABSTRACT FROM PUBLISHER]

Background and Objectives:For Evidence Based Medicine (EBM) learning journal clubs are recommended, but these are not common practice. How participants discuss and learn about applying evidence in other group meetings is unknown. We examined different types of group meetings and explored the use of, and discussions about, clinical research evidence. Methods:A mixed-methods study design was adopted. After distribution and analysis of a questionnaire about types of group meetings, interviews were conducted to better understand the most frequently occurring type. Results:GPs have different types of meetings, but the most common group meetings where evidence wass discussed were so called quality circles, i.e. pharmacotherapy audit meetings in which GPs discuss drug prescription figures or preferred treatment together with pharmacists. Interviews showed that the source of evidence used mostly are the recommendations in the national GP guidelines. The underlying evidence or new research did not play an important role in the discussions. Conclusions:Quality circles seem to be more goal-oriented than learning oriented. Learning discussions about controversies in clinical research or about the integration of evidence, patient values and clinical expertise occurred infrequently. To harvest the potential value of group meetings for EBM learning, quality circles in their present design are not optimal. [ABSTRACT FROM PUBLISHER]

Objectives Ethnohistoric accounts and archaeological research from Central California document a shift from the use of lower-cost, high-ranked resources (e.g., large game) toward the greater use of higher-cost, low-ranked resources (e.g., acorns and small seeds) during the Late Holocene (4500-200 BP). The subsistence transition from higher consumption of large game toward an increased reliance on acorns was likely associated with increases in levels of logistical mobility and physical activity. This study predicts that mobility and overall workload patterns changed during this transition to accommodate new food procurement strategies and incorporate new dietary resources during the Late Holocene in Central California. Materials and Methods Osteoarthritis prevalence was scored in the shoulder, elbow, hip, and knee of adult individuals ( n = 256) from seven archaeological sites in the Sacramento-San Joaquin Delta region. Comparisons were made between osteoarthritis prevalence, sex, age-at-death, and time period using ANCOVAs. Results The results of this study indicate significant increases in osteoarthritis prevalence in the hip of adult males and females during the Late Period (1200-200 BP), even after correcting for the cumulative effects of age. No differences were observed between the sexes or between time periods for the shoulder, elbow, and knee joints. Discussion The temporal increase in hip osteoarthritis supports the hypothesis that there was an increasing need for greater logistical mobility over time to procure key resources away from the village sites. Additionally, the lack of sex differences in osteoarthritis prevalence may suggest that females and males likely performed similar levels of activity during these periods. [ABSTRACT FROM AUTHOR]

Background: The LIRIK, an instrument for the assessment of child safety and risk, is designed to improve assessments by guiding professionals through a structured evaluation of relevant signs, risk factors, and protective factors. Objective: We aimed to assess the interrater agreement and the predictive validity of professionals' judgments made with the LIRIK in comparison to unstructured judgments. Method: In study 1, professionals made safety and risk judgments for 12 vignettes with the LIRIK (group 1, n = 36) or without an instrument (group 2, n = 43). In study 2, we compared professionals' safety and risk judgments for 370 children made with the LIRIK (group 1, n = 278) or with no instrument (group 2, n = 92), with outcomes indicating actual unsafety in files 6 months later. Results: In study 1, agreement about safety and risks was poor to moderate in both groups. Differences between groups were small and inconsistent. In study 2, the predictive validity of judgments was weak to moderate in both groups. In neither group had unsafe outcomes increased consistently when unsafety or risks were assessed as higher. Conclusions: Judgments made with the LIRIK were not more reliable or valid than unstructured professional judgments. These findings raise important questions about the value of risk assessment instruments and about how professional safety and risk judgments can be improved. [ABSTRACT FROM AUTHOR]

Disappointing results of recent tuberculosis chemotherapy trials suggest that knowledge gained from preclinical investigations was not utilized to maximal effect. A mouse-to-human translational pharmacokinetics (PKs) - pharmacodynamics (PDs) model built on a rich mouse database may improve clinical trial outcome predictions. The model included Mycobacterium tuberculosis growth function in mice, adaptive immune response effect on bacterial growth, relationships among moxifloxacin, rifapentine, and rifampin concentrations accelerating bacterial death, clinical PK data, species-specific protein binding, drug-drug interactions, and patient-specific pathology. Simulations of recent trials testing 4-month regimens predicted 65% (95% confidence interval [CI], 55-74) relapse-free patients vs. 80% observed in the REMox-TB trial, and 79% (95% CI, 72-87) vs. 82% observed in the Rifaquin trial. Simulation of 6-month regimens predicted 97% (95% CI, 93-99) vs. 92% and 95% observed in 2RHZE/4RH control arms, and 100% predicted and observed in the 35 mg/kg rifampin arm of PanACEA MAMS. These results suggest that the model can inform regimen optimization and predict outcomes of ongoing trials. [ABSTRACT FROM AUTHOR]

This study highlights the use of multiple methods for resolving a case of commingled human remains. Skeletal remains were located in a marijuana field in rural northern California by law enforcement. Although initially buried in shallow graves, the remains of two decedents were disturbed by large carnivores and scattered over a wide area. The remains were submitted by law enforcement for forensic anthropological analysis and resolution of commingling. To segregate the remains of the two individuals, a number of methods were employed, including: (i) physical matching of fragmented remains; (ii) articulation to evaluate joint congruence; (iii) visual pair-matching of bilateral elements; (iv) osteometric pair-matching; (v) evaluation of taphonomic patterns; (vi) DNA analysis; and (vii) portable X-ray spectrometry ( pXRF). This multimethod approach resulted in accurate resolution of the commingling and facilitated reconstruction of the biological profiles, taphonomic patterns, and trauma analysis for each individual. [ABSTRACT FROM AUTHOR]

Background and Objectives: The wide variability in pharmacokinetics of busulfan in children is one factor influencing outcomes such as toxicity and event-free survival. A meta-analysis was conducted to describe the pharmacokinetics of busulfan in patients from 0.1 to 26 years of age, elucidate patient characteristics that explain the variability in exposure between patients and optimize dosing accordingly.Patients and Methods: Data were collected from 245 consecutive patients (from 3 to 100 kg) who underwent haematopoietic stem cell transplantation (HSCT) in four participating centres. The inter-patient, inter-occasion and residual variability in the pharmacokinetics of busulfan were estimated with a population analysis using the nonlinear mixed-effects modelling software NONMEM VI. Covariates were selected on the basis of their known or theoretical relationships with busulfan pharmacokinetics and were plotted independently against the individual pharmacokinetic parameters and the weighted residuals of the model without covariates to visualize relations. Potential covariates were formally tested in the model.Results: In a two-compartment model, body weight was the most predictive covariate for clearance, volume of distribution and inter-compartmental clearance and explained 65%, 75% and 40% of the observed variability, respectively. The relationship between body weight and clearance was characterized best using an allometric equation with a scaling exponent that changed with body weight from 1.2 in neonates to 0.55 in young adults. This implies that an increase in body weight in neonates results in a larger increase in busulfan clearance than an increase in body weight in older children or adults. Clearance on the first day was 12% higher than that of subsequent days (p < 0.001). Inter-occasion variability on clearance was 15% between the 4 days. Based on the final pharmacokinetic-model, an individualized dosing nomogram was developed.Conclusions: The model-based individual dosing nomogram is expected to result in predictive busulfan exposures in patients ranging between 3 and 65 kg and thereby to a safer and more effective conditioning regimen for HSCT in children. [ABSTRACT FROM AUTHOR]

This review describes the developments in the radiation treatment of breast cancer based on some randomized European trials during the past decades. It will focus on the relevance of long term follow-up in breast cancer patients, starting with the surprising and important change in treatment results during follow-up shown in a locally advanced breast cancer trial. Breast conserving therapy (BCT) in stage I and II breast cancer was explored and tested in a randomized trial to prove equivalence between BCT and mastectomy. The positive outcome led to trials in breast conserving therapy with lower doses and partial breast irradiation. Finally the need for finding genetic profiles for predicting treatment response will be addressed in a trial with preoperative partial breast irradiation. [ABSTRACT FROM AUTHOR]

The article focuses on the achievements and contributions of the Knowledge Centre Religion and Development (KCRD) in the integration of religion in development programmes and policies. Topics discussed include the relation of religion with religious consevatism, terrorism, and fundamentalism, the importance of the notions of plurality and transformation on the works of KCRD, and secular or Muslim and Hindu versions of modernity.

Background: Education in evidence-based medicine (EBM) is an important part of the postgraduate training of GPs. Evaluation of its effect on EBM behaviour in daily clinical practice is difficult and instruments are scarce. Working in accordance with guidelines is considered as one of the key indicators of EBM behaviour.Objective: To develop and validate an instrument assessing guideline adherence of GP trainees in clinical practice.Methods: We developed an instrument that assesses guideline adherence, taking conscious deviation into account. The instrument assesses guideline adherence on 59 different management decisions (diagnosis N = 17, therapy N = 20, referral N = 22) for 23 conditions as described in 27 different clinical practice guidelines. We validated this instrument using performance data as collected by third-year GP trainees on three important properties: validity, reliability and feasibility.Results: Performance data were collected by 76 GP trainees on 12106 patient consultations with 12587 different reasons for encounter. Overall, guideline adherence was 82% (95% confidence interval 77-88%). The significant correlation with the national GP knowledge test (r 0.33, P 0.004) showed the instrument to be a valid instrument. Interrater reliabilities (intraclass correlation coefficient) varied between moderate and excellent (0.64-1.00, P < 0.001). The instrument proved feasible with coverage of 24% (N = 3082) of reasons for encounter presented to GP trainees and a mean and median time of 1 minute to score a patient consultation.Conclusion: This instrument proved valid, reliable and feasible to assess guideline adherence among trainees in the clinical primary care setting. [ABSTRACT FROM AUTHOR]

Assessment and decision-making in child maltreatment cases is difficult. Practitioners face many uncertainties and obstacles during their assessment and decision-making process. Research exhibits shortcomings in this decision-making process. The purpose of this literature review is to identify and discuss methods to overcome these shortcomings. We conducted a systematic review of the published literature on decision-making using PsychINFO and MEDLINE from 2000 through May 2014. We included reviews and quantitative research studies that investigated methods aimed at improving professional decision-making on child abuse and neglect in child welfare and child protection. Although many researchers have published articles on decision-making including ideas and theories to improve professional decision-making, empirical research on these improvements is scarce. Available studies have shown promising results. Structured decision-making has created a greater child-centred and holistic approach that takes the child's family and environment into account, which has made practitioners work more systematically and improved the analysis of complex situations. However, this approach has not improved inter-rater agreement on decisions made. Shared decision-making may improve the participation of parents and children and the quality of decisions by taking client treatment preferences into account in addition to scientific evidence and clinical experience. A number of interesting developments appear in recent research literature; however, child welfare and child protection must find additional inspiration from other areas, e.g., mental health services, because research on decision-making processes in child welfare and child protection is still rare. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have shown that clinical queries are common among doctors. Data on the information-seeking behaviour of general practice (GP) trainees are scarce though, and numbers studied are small.Objective: The objective of this study was to determine how often and how GP trainees search for answers to clinical queries encountered in daily clinical practice.Methods: Third-year GP trainees kept logs on all patient contacts for eight consecutive practice days. Information was obtained on patient contacts (description), clinical queries (frequency, type), seeking behaviour (frequency, moment, reason not to search, resources used, duration of search) and answers (frequency, impact). Descriptive analyses were performed; frequencies and percentages were computed. We calculated the number of clinical queries per patient, the number of searches per query and the number of answers per search.Results: Seventy-six trainees reported 1533 clinical queries about 7300 patients presenting 7619 complaints [mean of 0.2 queries per patient, standard deviation (SD) 0.1]. For most of the queries trainees pursued an answer (mean of 0.8 per query, SD 0.2), mostly during consultation (61% of searches), and frequently retrieved answers (mean of 0.8 per search, SD 0.17) they reported to improve clinical decision making in 26%. Most common resources were colleagues or supervisors (28%), and national GP guidelines (26%). The median duration of a search was 4 minutes (interquartile range 3).Conclusion: GP trainees have one clinical query per five patients. They often attempted to find answers and reported to succeed in most of the searches, primarily by consulting supervisors or colleagues and national GP guidelines. [ABSTRACT FROM AUTHOR]

Since the 1980s, cremation has become the fastest growing area of the U.S. funeral industry. At the same time, the number of litigations against funeral homes and cremation facilities has increased. Forensic anthropologists are often asked to determine whether the contents of an urn are actually cremated bone, and to address questions regarding the identity of the remains. This study uses both metric and chemical analyses for resolving a case of contested cremains. A cremains weight of 2021.8 g was predicted based on the decedent's reported stature and weight. However, the urn contents weighed 4173.5 g. The urn contents also contained material inconsistent with cremains (e.g., moist sediment, stones, ferrous metal). Analysis using XRD and SEM demonstrated that the urn contained thermally altered bone as well as inorganic material consistent with glass fiber cement. Although forensically challenging, cremains cases such as this one can be resolved using a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Pelvic ring fractures are associated with high rates of mortality and thus can provide key information about circumstances surrounding death. These injuries can be particularly informative in skeletonized remains, yet difficult to diagnose and interpret. This study adapted a clinical system of classifying pelvic ring fractures according to their resultant degree of pelvic stability for application to gross human skeletal remains. The modified Tile criteria were applied to the skeletal remains of 22 individuals from the Cleveland Museum of Natural History and Universidad Nacional Autónoma de México that displayed evidence of pelvic injury. Because these categories are tied directly to clinical assessments concerning the severity and treatment of injuries, this approach can aid in the identification of manner and cause of death, as well as interpretations of possible mechanisms of injury, such as those typical in car-to-pedestrian and motor vehicle accidents. [ABSTRACT FROM AUTHOR]

Summary Background Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. Methods Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov , number NCT02295033 . Findings Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17·2 years (IQR 13·0–19·0). 20-year overall survival was 59·7% (99% CI 56·3–63·0) in the boost group versus 61·1% (57·6–64·3) in the no boost group, hazard ratio (HR) 1·05 (99% CI 0·92–1·19, p=0·323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0·65 (99% CI 0·52–0·81, p<0·0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16·4% (99% CI 14·1–18·8) in the no boost group versus 12·0% (9·8–14·4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1·8% (99% CI 1·1–2·5) in the no boost group versus 5·2% (99% CI 3·9–6·4) in the boost group (p<0·0001). Interpretation A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years. Funding Fonds Cancer, Belgium. [ABSTRACT FROM AUTHOR]

Background: Practitioners investigating cases of suspected child maltreatment often disagree whether a child is subject to or at risk of abuse or neglect in the family and, if so, what to do about such abuse or neglect. Structured decision-making is considered to be a solution to the problem of subjective judgments and decisions. Objective: This study investigates the effects of ORBA, a method for structured decision-making in Advice and Reporting Centres for Child Abuse and Neglect (ARCCAN), on interrater agreement of judgments and decisions. Methods: Two groups of ARCCAN practitioners, one trained in using ORBA and one untrained, used a questionnaire to make judgments and decisions on the same case vignettes. Interrater agreement on the judgments was obtained by calculating the percentage of agreement, intra class correlation, and the Kappa coefficient. Results: Both ORBA trained and untrained practitioners showed little agreement on judgments and decisions, except for the judgment on child maltreatment substantiation, for which trained practitioners showed fair agreement. Agreement among trained and untrained practitioners only differed for some judgments and decisions, and differences were not always in the same direction. Conclusions: This result indicates no convincing evidence that structured decision-making leads to better agreement on decisions concerning child abuse and neglect. Recommendations for improvements in uniform decision-making and further research are given. [ABSTRACT FROM AUTHOR]

Previous research has demonstrated significant sexual dimorphism in friction ridge skin characteristics. This study uses a novel method for measuring sexual dimorphism in finger ridge breadths to evaluate its utility as a sex estimation method from an unknown fingerprint. Beginning and ending in a valley, the width of ten parallel ridges with no obstructions or minutia was measured in a sample of 250 males and females ( N = 500). The results demonstrate statistically significant differences in ridge breadth between males and females ( p < 0.001), with classification accuracy for each digit varying from 83.2% to 89.3%. Classification accuracy for the pooled finger samples was 83.9% for the right hand and 86.2% for the left hand, which is applicable for cases where the digit number cannot be determined. Weight, stature, and to a lesser degree body mass index also significantly correlate with ridge breadth and account for the degree of overlap between males and females. [ABSTRACT FROM AUTHOR]

Abstract: Evaluation of diagenesis in bioapatite samples is an important step for screening bone and tooth samples for stable isotope analysis to ensure in vivo signatures are obtained. Fourier transform infrared (FTIR) spectroscopy is one tool used to evaluate diagenesis by anthropological geochemists and commonly employs calculating the infrared splitting factor (IR-SF) and carbonate-to-phosphate ratio (C/P). There are three commonly used sample preparation techniques for vibrational spectroscopy: transmission FTIR, attenuated total reflection (ATR), and diffuse reflectance infrared Fourier transform (DRIFT). Each technique characterizes the internal vibrations of particular molecular groups, such as carbonate (CO3) and phosphate (PO4), using different optical properties to detect absorbance bands. Spectra are correlated between techniques using correction equations that account for differences in optical properties. Traditionally, anthropologists have used spectra produced by transmission FTIR to assess diagenesis, most commonly using two indices (IR-SF and C/P); however, recently the ATR and DRIFT techniques have been used as an alternative to transmission FTIR. The spectra produced by the three techniques are thought to be interchangeable in calculating the indices used to assess diagenesis. In this study, we evaluated the interchangeability of the three FTIR techniques by analyzing 452 prehistoric and modern bioapatite samples. Results indicate that IR-SF and C/P values are not equivalent between the three techniques. However, ATR produced more reliable results and was comparable to transmission FTIR. The DRIFT method showed much lower resolution, and did not distinguish between modern and prehistoric bioapatite samples as clearly. [Copyright &y& Elsevier]

The application of stable isotope analysis has provided novel approaches for provenancing unidentified human remains from forensic contexts. Stable isotope ratios measured in human tissues provide a record of the foods consumed during life as well as the geographic location where drinking water or food was obtained. This study begins with an overview of the application of stable isotope analysis for provenancing human remains, followed by three cases that illustrate how chemical signatures in bone reflect a probable region of origin. Using stable carbon and nitrogen isotopes of human bone, we test whether human skeletal remains recovered by the Joint POW/MIA Accounting Command-Central Identification Laboratory (JPAC-CIL, or CIL) reflect a geographic origin within North America or Asia. Stable carbon and nitrogen isotopes of human bone collagen and stable carbon isotopes of bone apatite reflect consumption of food resources that are expected to vary between world regions due to cultural dietary differences. Based on the isotopic differences, a testable hypothesis of geographic origin can be applied, determining if the remains are more likely of a U.S. service person or of an indigenous local. We believe that this approach can provide useful information for narrowing search parameters in unidentified persons cases; can contribute to human rights cases where an unknown individual is thought to originate from a different geographic area; and, in human remains cases of unknown geographic provenience, can determine whether a person is local or nonlocal. [ABSTRACT FROM AUTHOR]

Busulfan (Bu) is used as a myeloablative agent in conditioning regimens before allogeneic hematopoietic cell transplantation (allo-HCT). In line with strategies explored in adults, patient outcomes may be optimized by replacing cyclophosphamide (Cy) with or without melphalan (Mel) with fludarabine (Flu). We compared outcomes in 2 consecutive cohorts of HCT recipients with a nonmalignant HCT indication, a myeloid malignancy, or a lymphoid malignancy with a contraindication for total body irradiation (TBI). Between 2009 and 2012, 64 children received Flu + Bu at a target dose of 80-95 mg·h/L, and between 2005 and 2008, 50 children received Bu targeted to 74-80 mg·h/L + Cy. In the latter group, Mel was added for patients with myeloid malignancy (n = 12). Possible confounding effects of calendar time were studied in 69 patients receiving a myeloablative dose of TBI between 2005 and 2012. Estimated 2-year survival and event-free survival were 82% and 78%, respectively, in the FluBu arm and 78% and 72%, respectively, in the BuCy (Mel) arm (P = not significant). Compared with the BuCy (Mel) arm, less toxicity was noted in the FluBu arm, with lower rates of acute (noninfectious) lung injury (16% versus 36%; P = .007), veno-occlusive disease (3% versus 28%; P = .003), chronic graft-versus-host disease (9% versus 26%; P = .047), adenovirus infection (3% versus 32%; P = .001), and human herpesvirus 6 infection reactivation (21% versus 44%; P = .005). Furthermore, the median duration of neutropenia was shorter in the FluBu arm (11 days versus 22 days; P < .001), and the patients in this arm required fewer transfusions. Our data indicate that Flu (160 mg/m2) with targeted myeloablative Bu (90 mg·h/L) is less toxic than and equally effective as BuCy (Mel) in patients with similar indications for allo-HCT. [ABSTRACT FROM AUTHOR]

Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women. Eighty percent of Ugandan participants were severely food insecure, 26% lost weight ante-partum, and median BMI post-partum was only 20.2 kg/m2. Rich PK-data of normally nourished (pregnant) women and healthy Ugandans established prior information. Overall, drug exposure was reduced (LPV −33%, EFV −15%, ritonavir −17%) compared to well-nourished controls ( P < 0.001), attributable to decreased bioavailability. Pregnancy increased LPV/r clearance 68% ( P < 0.001), whereas EFV clearance remained unchanged. Hair concentrations correlated with plasma-exposure ( P < 0.001), explaining 29% PK-variability. In conclusion, pregnancy and food insecurity were associated with lower ART exposures in this cohort of predominantly underweight women, compared to well-nourished women. Much variability in plasma-exposure was quantified using hair concentrations. Addressing malnutrition as well as ART-PK in this setting should be a priority. [ABSTRACT FROM AUTHOR]

ABSTRACT This article evaluates age of weaning and early childhood diets of eight males and nine females from a Middle Holocene (4300-3000 BP) site in Central California, CA-CCO-548. All individuals died as adults. δ15N values from serial sections of dentin collagen in first molars suggest females were fully weaned, on average, by 3.6 years of age, about 0.4 years later than males in the sample, suggesting possible greater parental investment in female offspring. However, throughout childhood females consumed lower trophic-level foods than males. This could indicate greater investment in males through provisioning of higher quality foods, or alternatively, some degree of independent foraging by males starting as early as 2 to 3 years of age. Even as adults, these same males and females consumed a different range of foods as indicated by their bone collagen δ13C and δ15N values. Overall, the data suggest children were enculturated early into their respective gendered diets, with girls consuming greater amounts of plant foods and boys consuming greater amounts of higher-trophic level fish and meat protein. Am J Phys Anthropol 152:471-483, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: N, N-dimethylacetamide (DMA) is administered to children during high-dose chemotherapy as a solubilizer with the intravenous formulation of busulfan (Busilvex). DMA has shown liver toxicity in rats. However, little is known regarding its pharmacokinetics (PK) in humans. The aim of this analysis was to compare the PK of DMA after a once-daily dose of Busilvex with the standard scheme consisting of 3-4 administrations per day in children. Methods: Out of 42 children, aged 0.1-18.9 years, receiving Busilvex, 18 children received the first dose as a loading dose, giving a double dose of 1.4-2.0 mg/kg over a 4 h infusion followed by 15 doses of 0.7-1.0 mg/kg as 2 h infusions every 6 h. The other 24 children received Busilvex as 3 h infusions once-daily for 4 consecutive days with a targeted busulfan AUC of 4,263 μM*min. Using NONMEM™ plasma, concentration-time data were analyzed. Assuming an increase in clearance overtime as found in our previous investigation, separate time factors for the two different dosing schedules included in the dataset were tested. Results: A one-compartment model with clearance increasing over time described the DMA kinetics sufficiently. Peak plasma concentrations of DMA, up to 3.09 mmoL/L (median 0.75 mmoL/L) for the current licensed dose regimen and up to 8.77 mmoL/L (median 3 mmoL/L) for the once-daily application, were observed. The examined increase in clearance was found to be 58 mL/h/kg and 6.1 mL/h/kg per day for the current licensed and the once-daily dose regimen, respectively. Conclusion: N, N-dimethylacetamide as solvent of lipophilic drugs such as busulfan has a linear PK in children of all ages using a dose split into one or four administrations per day. The rapid clearance with different dosing in patients of different body weights indicates that it is safe to use DMA in children in both a once and four times daily regimen. [ABSTRACT FROM AUTHOR]

Abstract: ORBA is a method that aims to improve decision making about suspected child maltreatment in Advice and Reporting Centres of Child Abuse and Neglect (ARCCAN). It structures the process of judging and deciding and makes it explicit by distinguishing separate steps, and by identifying the necessary information to consider and the judgments and decisions to be made in each step. In this study it was investigated whether decision making in ARCANNs has become more systematic and transparent, since the implementation of ORBA. The contents of 100 case records from 2010 were analyzed, after ORBA had been implemented in all agencies, to see to what extent these records contained relevant information, and to what extent process steps and rationales for decisions could be identified. This was compared with the contents of 60 records of three agencies from 2005, before ORBA was implemented. Analyses showed that in 2010 records more often contained relevant information and process steps that ORBA prescribes than in 2005. It was salient however that rationales for judgments and decisions were still often absent in 2010. While after ORBA''s introduction the process has clearly become more systematic and more transparent, compared to 2005, more improvements are still called for, specifically in explicitly motivating decisions. Explanations and implications of our results are discussed. [Copyright &y& Elsevier]

Abstract: The severity of complications of allogeneic hematopoietic stem cell transplantation (HSCT) is governed mainly by the status of immune reconstitution. In this study, we investigated differences in immune reconstitution with different cell sources and the association between the kinetics of immune reconstitution and mortality. Immunophenotyping was performed every 2 weeks in children who had undergone HSCT between 2004 and 2008 at University Medical Center Utrecht. Lymphocyte reconstitution in the first 90 days after HSCT was studied in relation to mortality in 3 HSCT groups: matched sibling bone marrow (BM) recipients (35 patients), unrelated BM recipients (32 patients), and unrelated cord blood recipients (36 patients). The median age of recipients was 5.9 years (range, 0.1-21 years). The nature and speed of T cell, B cell, and natural killer (NK) cell reconstitution were highly dependent on the cell source. In the first 90 days after HSCT, faster B cell and NK cell reconstitution and delayed T cell reconstitution were shown in unrelated cord blood recipients compared with matched sibling BM and unrelated BM recipients. Of the lymphocyte subsets investigated, a large number of NK cells and a more rapid CD4+ immune reconstitution over time, resulting in sustained higher CD4+ counts, were the only predictors of a lower mortality risk in all cell sources. The final model showed that during the first 90 days, patients with an area under the CD4+ cell receiver- operating curve of >4,300 cells/day and no peak in CD4+ cell counts had the highest likelihood of survival (hazard ratio for mortality, 0.2; 95% confidence interval, 0.06-0.5). Our data indicate that CD4+ kinetics may be used to identify patients at greatest risk for mortality early after HSCT. [Copyright &y& Elsevier]

Abstract: In contrast to most new oncology treatments, wide clinical introduction of partial breast irradiation (PBI) is not based on level A trial evidence. Despite promising phase I/II data, new reports based upon large cohorts of patients mention more recurrences and/or complications from PBI compared with whole breast irradiation (WBI), necessitating more careful selection of patients for PBI while awaiting long term results of major clinical trials. In an attempt to improve this we give preoperative PBI within a prospective trial. [Copyright &y& Elsevier]

A consensus conference was held in order to provide guidelines for the use of adjuvant therapy in patients with Stage I carcinoma of the breast, using traditional information, such as tumor size, microscopic character, Nottingham index, patient age and co-morbidities, but also incorporating steroid hormone and Her-2-neu data as well as other immunohistochemical markers. The role of the genetic analysis of breast cancer and proprietary gene prognostic signatures was discussed, along with the molecular profiling of breast cancers into several groups that may predict prognosis. These molecular data are not currently sufficiently mature to make them part of decision making algorithms of recommendations for the treatment of individual patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: The wide variability in pharmacokinetics of busulfan in children is one factor influencing outcomes such as toxicity and event-free survival. A meta-analysis was conducted to describe the pharmacokinetics of busulfan in patients from 0.1 to 26 years of age, elucidate patient characteristics that explain the variability in exposure between patients and optimize dosing accordingly. Patients and Methods: Data were collected from 245 consecutive patients (from 3 to 100 kg) who underwent haematopoietic stem cell transplantation (HSCT) in four participating centres. The inter-patient, inter-occasion and residual variability in the pharmacokinetics of busulfan were estimated with a population analysis using the nonlinear mixed-effects modelling software NONMEM VI. Covariates were selected on the basis of their known or theoretical relationships with busulfan pharmacokinetics and were plotted independently against the individual pharmacokinetic parameters and the weighted residuals of the model without covariates to visualize relations. Potential covariates were formally tested in the model. Results: In a two-compartment model, body weight was the most predictive covariate for clearance, volume of distribution and inter-compartmental clearance and explained 65%, 75% and 40% of the observed variability, respectively. The relationship between body weight and clearance was characterized best using an allometric equation with a scaling exponent that changed with body weight from 1.2 in neonates to 0.55 in young adults. This implies that an increase in body weight in neonates results in a larger increase in busulfan clearance than an increase in body weight in older children or adults. Clearance on the first day was 12% higher than that of subsequent days (p < 0.001). Inter-occasion variability on clearance was 15% between the 4 days. Based on the final pharmacokinetic-model, an individualized dosing nomogram was developed. Conclusions: The model-based individual dosing nomogram is expected to result in predictive busulfan exposures in patients ranging between 3 and 65 kg and thereby to a safer and more effective conditioning regimen for HSCT in children. [ABSTRACT FROM AUTHOR]

Researchers have long debated the appropriateness of stable isotope analysis of bone apatite to reconstruct the diets of ancient animals. The debate has centred, in part, on diagenesis of bone mineral from interaction with the burial environment. A number of acetic acid treatments are used to remove diagenetic carbonates from samples; however, less is known on how different protocols alter stable isotope values. We compare two common acetic acid solution treatments (0.1 M versus 1.0 M-buffered) to examine the effects on carbon and oxygen isotope values and Fourier transform infrared spectroscopy (FTIR) spectra in human bone from different burial contexts. Results indicate that both treatments have a similar effect on isotope values and FTIR spectra in bone apatite. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarctions at different locations have been related to different sets of risk factors. This study was designed to examine the association between cardiovascular risk factors and specific coronary artery calcification (CAC).Methods: The study population comprised 573 postmenopausal women selected from a population-based cohort study. Established vascular risk factors were measured. The women underwent a multi detector-row computed tomography (16- MDCT) (Philips Mx 8000 IDT 16) to assess coronary calcium. The Agatston score was used to quantify coronary calcium. Logistic regression models were utilized to assess the relations.Results: The prevalence of coronary artery calcification (Agatston score>0) was 61.5% (n=348). CAC was most common in the left anterior descending (LAD) artery with a prevalence of 43.9%; and the rates of prevalence in the right coronary artery (RCA), the circumflex (LCX), the left main artery (LM), and the posterior descending artery (PDA) were 23.1%, 19.4%, 15.8%, and 0.3%, respectively. In the multivariate regression models, age was predominantly related to the calcification in the LAD and LCX, low density lipoprotein to calcification in the LAD, and cholesterol to the calcification of the RCA. Hypertension and systolic & diastolic blood pressures were related to the calcification of the LCX, whereas smoking was predominantly related to the calcification of both LAD and RCA. Finally, age, body mass index, and systolic blood pressure were significantly related to the calcification in the LM.Conclusion: Our findings showed that the consequences of elevated risk factor levels on the development of atherosclerosis appeared to be different across the segments of the coronary arteries. [ABSTRACT FROM AUTHOR]