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Objectives: Adequate analytical quality of reported results is primarily ensured by performing internal quality control (iQC). Currently, several different iQC practices are in use. As a prelude to the revision of a Dutch guidance document on analytical QC, a questionnaire was sent out to gain insights in the applied practices and the need for guidance., Methods: A questionnaire, containing 20 multiple-choice questions with possibilities for explanation and comment on iQC practices and aspects was distributed to all clinical chemistry laboratories within the Netherlands. Results were reported descriptively., Results: Responses were received from 27 clinical laboratories (response 43 %). In 30 % the iQC was based on the analytical characteristics only, while 30 % used a 6-Sigma method, 19 % risk-based beyond 6-Sigma and 22 % used an alternative approach. 89 % of laboratories used a virtual analyzer model for iQC setup within one or more laboratory sites. Practices for determining standard deviation (SD) values included determining SD for each new iQC material (35 %), using historical SD values for new materials (35 %), and incorporating clinical tolerances into the SD value (31 %). Furthermore, 44 % of laboratories used patient moving averages for one or more tests. Daily iQC management was based on either "traffic lights" indicating in or out of control status, and review of all QC charts, often using multiple software systems., Conclusions: A large heterogeneity of iQC practices in clinical laboratories was observed in the Netherlands. Several starting points for further research and/or guidance were identified, particularly in relation to the determination of SD values, the virtual analyzer model and methods to ensure analyzer equivalence., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Lactose intolerance is defined as the presence of gastrointestinal symptoms, such as bloating, abdominal pain or diarrhoea, after consumption of lactose in individuals with lactose malabsorption. Most cases involve primary lactose intolerance, caused by a loss of activity of the enzyme lactase, needed for digestion of lactose. A traditional method of establishing lactose intolerance is the hydrogen breath test (HBT), accompanied by a questionnaire to document complaints experienced by the patient during the test. Due to knowledge on lactase-persistent alleles, DNA genotyping has become available for the diagnostic work-up for lactose intolerance. Both methods are currently in use. The aim of this study is to provide a definite diagnostic approach for patients suspected of lactose intolerance in a Dutch population., Methods: In this retrospective, observational study, patients aged 15 years or older were included after presenting to their treating physician with symptoms suggestive of lactose intolerance. HBT, including a questionnaire to document complaints and DNA genotyping of LCT-13,910 C/T was performed for each patient as part of a routine diagnostic work-up., Results: 1101 patients were included (29% men). Positive and negative predictive value, sensitivity and specificity of HBT versus DNA genotyping were 80% (CI 75-84), 97% (CI 96-98), 89% (CI 84-92) and 94% (92-96) respectively. The use of the questionnaire added little diagnostic value., Conclusions: In a population with a high prevalence of lactase-persistent alleles, we advise to exclude HBT from the diagnostic route for suspected lactose intolerance, and replace it with genotyping of lactase-persistent alleles.

Background: High-quality malaria diagnosis is essential for effective treatment and clinical disease management. Microscopy and rapid diagnostic tests are the conventional methods performed as first-line malaria diagnostics in non-endemic countries. However, these methods lack the characteristic to detect very low parasitaemia, and accurate identification of the Plasmodium species can be difficult. This study evaluated the performance of the MC004 melting curve-based qPCR for the diagnosis of malaria in routine clinical practice in non-endemic setting., Methods and Results: Whole blood samples were collected from 304 patients with clinical suspicion of malaria and analysed by both the MC004 assay and conventional diagnostics. Two discrepancies were found between the MC004 assay and microscopy. Repeated microscopic analysis confirmed the qPCR results. Comparison of the parasitaemia of nineteen Plasmodium falciparum samples determined by both microscopy and qPCR showed the potential of the MC004 assay to estimate the parasite load of P. falciparum. Eight Plasmodium infected patients were followed after anti-malarial treatment by the MC004 assay and microscopy. The MC004 assay still detected Plasmodium DNA although no parasites were seen with microscopy in post-treatment samples. The rapid decline in Plasmodium DNA showed the potential for therapy-monitoring., Conclusion: Implementation of the MC004 assay in non-endemic clinical setting improved the diagnosis of malaria. The MC004 assay demonstrated superior Plasmodium species identification, the ability to indicate the Plasmodium parasite load, and can potentially detect submicroscopic Plasmodium infections., (© 2023. The Author(s).)

Introduction: The CYP2C19 enzyme converts clopidogrel into an active metabolite. Carriers of CYP2C19 loss-of-function (LOF) variants with a history of ischemic stroke or transient ischemic attack (TIA) using clopidogrel may have a higher risk of recurrent stroke. To study the implications of genetic CYP2C19 heterogeneity in treatment of cerebral ischemia, knowledge about the prevalence of CYP2C19 LOF variants within the population is important. We investigated the frequency of CYP2C19 LOF variants in patients with non-cardioembolic ischemic stroke or TIA in the Dutch population., Methods: We performed a single-center observational study with a cross-sectional design in a Dutch thrombectomy-capable stroke center. We included all patients presenting with non-cardioembolic ischemic stroke or TIA. We determined the frequency of CYP2C19 LOF variants in the full cohort. Additionally, we compared the frequency of CYP2C19 LOF variants in two subgroups: patients with first-ever non-cardioembolic ischemic stroke or TIA versus patients with recurrent ischemic stroke or TIA using clopidogrel because of a history of ischemic stroke or TIA., Results: We enrolled 410 patients between January 1, 2021, and July 1, 2021. 109 (26.6%) patients were carriers of CYP2C19 LOF variants. We found no difference in the frequency of CYP2C19 LOF variants between patients with first-ever ischemic stroke or TIA versus patients with recurrent ischemic stroke or TIA using clopidogrel (25.9 vs. 31.9%, respectively, p = 0.31)., Discussion and Conclusion: About a quarter of patients with non-cardioembolic ischemic stroke or TIA in the Dutch population carry a CYP2C19 LOF variant. This is lower than estimates found in studies with Asian populations but similar to estimates found among Caucasian patients in other parts of the world., (© 2023 S. Karger AG, Basel.)

Purpose: Around 20%-30% of patients treated with fluoropyrimidines develop severe treatment-related adverse events (AEs). These are mainly caused by deficiency of dihydropyrimidine dehydrogenase, its main metabolizing enzyme. The DPYD *7 variant allele contains a frameshift mutation that leads to absence of dihydropyrimidine dehydrogenase. Clinical studies on this variant in patients treated with fluoropyrimidines are lacking because of its low minor allelic frequency. However, the DPYD *7 minor allelic frequency is 56-times higher in the Dutch compared with the global population. This allowed us to evaluate fluoropyrimidine tolerability in DPYD *7 variant allele carriers., Materials and Methods: Patients treated with standard-of-care fluoropyrimidine who were pretreatment DPYD genotyped for DPYD*2A , *13 , 2846A>T , and 1236G>A single-nucleotide polymorphisms were included for analyses. Patients were additionally screened for the DPYD *7 allele (rs72549309, 295-298delTCAT). AEs were graded if they worsened from baseline, according to Common Terminology Criteria for Adverse Events version 5.0. AEs ≥ grade 3 were considered severe., Results: From 3,748 patients, we found 13 patients carrying heterozygous DPYD*7 . Relevant clinical data were available for 11 patients. All patients developed fluoropyrimidine-related AEs, of which five patients developed severe AEs (46%). From these five patients, three patients were started with 65% or 50% of standard dose, but apparently still developed severe toxicity. Because of severe AEs, three patients discontinued treatment prematurely (one patient already started with 50% of standard dose) and one patient who started with 50% of standard dose was further reduced to 35% of standard dose., Conclusion: In this study, the clinical consequences of carrying the DPYD *7 variant allele were confirmed as 46% of the patients developed severe AEs, even in the presence of initial dose reductions. This underlines the need for prospective studies investigating the required fluoropyrimidine dose for DPYD *7 carriers.

Children who experience well-being are engaging more confidently and positively with their caregiver(s) and peers, which helps them to profit more from available learning opportunities and support current and later life outcomes. The goodness-of-fit theory suggests that children's well-being might be a result of the interplay between their temperament and the environment. However, there is a lack of studies that examined the association between children's temperament and well-being in early childhood education and care (ECEC), and whether this association is affected by ECEC process quality. Using a multilevel random coefficient approach, this study examines the association between toddlers' ( N = 1,561) temperament (shyness, emotionality, sociability, and activity) and well-being in Norwegian ECEC and investigates whether process quality moderates this association. Results reveal an association between temperament and well-being. Staff-child conflict moderates the association between shyness and well-being, and between activity and well-being. Moreover, high emotional behavioral support moderates the association between activity and well-being. Extra attention should be paid by the staff to these children's needs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 van Trijp, Lekhal, Drugli, Rydland, van Gils, Vermeer and Buøen.)

As a consequence of the outbreak of the Coronavirus Disease 2019 (COVID-19) child care facilities all over the world were temporarily closed to minimize the spread of the virus. In Netherlands, the first closure lasted for almost 2 months. The return to the child care center after this significant interruption was expected to be challenging, because earlier studies demonstrated that transitions into child care can be stressful for both children and their parents. The current paper retrospectively examined the distress of Dutch children (aged 0-4) and their parents during the first 2 weeks after the reopening of child care centers, and what factors accounted for individual differences in distress. In total, 694 parents filled out an online questionnaire about stress during closure and distress after the reopening of child care centers. Furthermore, questions regarding several demographic variables and child care characteristics were included, as well as questionnaires measuring child temperament, parental separation anxiety, and parental perception of the child care quality. Results showed that younger children and children with parents scoring higher on separation anxiety experienced more distress after the reopening, as reported by parents. Furthermore, children were more distressed upon return when they attended the child care center for less hours per week after the reopening, experienced less stress during closure, and grew up in a one-parent family. With regard to parental distress after the reopening, we found that parents scoring higher on separation anxiety and fear of COVID-19 experienced more distress. Moreover, parents experiencing less stress during closure and mothers were more distressed when the child returned to the child care center. Finally, concurrent child and parental distress after reopening were positively related. The results of the current study may help professional caregivers to identify which children and parents benefit from extra support when children return to the child care center after an interruption. Especially the role that parental separation anxiety played in predicting both child and parental distress deserves attention. More research is required in order to study the underlying mechanisms of these associations and to design appropriate interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Vet, Vrijhof, van der Veek, Pieplenbosch, van Bakel and Vermeer.)

The current study examined the attachment development of 92 internationally adopted Chinese girls, focusing on the influence of type of pre-adoption care (institutional versus foster care) and sensitive adoptive parenting. Although the children were more often insecurely attached than non-adopted children 2 and 6 months after adoption (Times 1 and 2, N = 92), they had similar levels of secure base script knowledge (SBS knowledge) as a non-adopted comparison group at age 10 (Time 3, N = 87). Furthermore, concurrently observed sensitive parenting was positively associated with SBS knowledge. Finally, a significant interaction between type of pre-adoption care and early-childhood sensitive parenting indicated that the post-institutionalized children showed a stronger increase in security than the post-foster children when parents were more sensitive.

In a previous study, we examined hair cortisol concentrations (HCCs) in children when first entering elementary school (at 4 years). In this follow-up study, we examined their HCC when they entered third grade (at 6 years), where the more playful first grades proceed into a more formal learning setting. Participants were 30 6-year-old children (14 boys). Hair samples (≥5 cm) were collected 2 months after the summer holidays. Hair analysis was conducted using two 2-cm long segments, reflecting the first 2 months of school attendance in grade 3 (the scalp-near segment), and 2 months prior to the start in grade 3. Between these two sections, we left a gap of 1 cm to avoid overlap of periods (due to differences in hair growth rate). Children showed a significant increase in cortisol levels when they entered third grade. This increase was not associated with social fearfulness or academic achievement, but did show significant associations with inhibitory control: children with less inhibitory control had higher cortisol levels after entering third grade, and larger increases in cortisol than children with higher scores on inhibitory control. This suggests that the ability to inhibit or control impulsive responsivity is important for children's stress regulation when making the transition to a more formal school environment.

Foster and adoptive parents often face challenges while taking care of children who, due to their adverse early life experiences, are at risk of developing insecure attachment relationships, behavior problems, and stress dysregulation. Several intervention programs have been developed to help foster and adoptive parents to overcome these challenges. In the current study, a series of eight meta-analyses were performed to examine the effectiveness of these intervention programs on four parent outcomes (sensitive parenting, k = 11, N = 684; dysfunctional discipline, k = 4, N = 239; parenting knowledge and attitudes, k = 7, N = 535; parenting stress, k = 18, N = 1,306), three child outcomes (attachment security, k = 6, N = 395; behavior problems, k = 33, N = 2,661; diurnal cortisol levels, k = 3, N = 261), and placement disruption (k = 7, N = 1,100). Results show positive effects for the four parent outcomes and child behavior problems, but not for attachment security, child diurnal cortisol levels, or placement disruption. Indirect effects on child outcomes may be delayed, and therefore long-term follow-up studies are needed to examine the effects of parenting interventions on children.

The aim of this study was to determine whether the Hem-Col method of obtaining and storing blood is an acceptable alternative to venepuncture for measuring Diabetes Care parameters. Design and methods : Hem-Col is a novel blood collection device that is designed to collect capillary blood drawn with a finger prick. Hem-Col is a microtube containing an anticoagulant and a preservation buffer to enhance analyte stability in whole blood. The Diabetes Care parameters cholesterol, creatinine, HbA1c, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides were measured both in blood/plasma collected via Hem-Col and blood/plasma collected with venepuncture. The results were compared to assess the agreement between the two methods. Results : HbA1c shows agreement after storage for up to 120 hours at temperatures ranging from 4 to 37 °C. Cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and creatinine can be measured after 120 hours of storage in Hem-Col buffer, if high temperatures are avoided, and with the use of correction factors or adaptations to reported reference intervals. Conclusion : Hem-Col is suitable for the measurement of HbA1c after storage for up to 120 hours at temperatures ranging from 4 to 37 °C. Cholesterol, creatinine, HDL cholesterol, LDL cholesterol and triglycerides can be measured after 120 hours of storage in Hem-Col buffer, if high temperatures are avoided. Further studies are required to determine whether Hem-Col can replace the venepuncture for the Diabetes Care parameters., Competing Interests: FV, RC and HV hold an equity interest in Labonovum B.V. and serve in an uncompensated advisory/consulting role for Labonovum B.V.. MH declares no conflict of interest., (© 2019 The Authors.)

This lab quiz presents some practical case studies on the correct use of D-dimer tests in patients suspected of venous thromboembolism. Elevated D-dimer levels are associated with clotting activation and fibrinolysis and can be used as indirect biomarkers of thrombosis. The D-dimer test is highly sensitive and is used to rule out the presence of venous thromboembolism (VTE) when clinical probability is low, based on Wells scores. However, sensitivity and specificity of cut-off values for D-dimer for ruling out VTE are strongly assay-dependent due to lack of standardisation. Because of low specificity, use of these cut-off values is problematic in cases of sepsis and inflammation, after recent surgery and in cases of trauma and active malignancy as well as during anticoagulant therapy and pregnancy. Agedependent cut-off values for patients > 50 years old might improve specificity and could be safely used if clinically validated assays (latex-agglutination assays) are used as described for the ADJUST-study.

Paroxysmal nocturnal hemoglobinuria (PNH), a rare benign hematological disorder, presents with a wide variety of clinical symptoms. A direct Coombs-negative hemolytic anemia combined with an increased LDH = Lactate dehydrogenase level are signs to test for PNH. Follow-up does not need any microscopic review's only flow cytometric PNH clone size.

Background: Foster children are at higher risk of the development of behavior and emotional problems, which can contribute to the development of insecure attachment bonds with their foster parents and (subsequently) to placement breakdown. Sensitive parenting might minimize the adverse effects of the behavior and emotional problems. Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline in Foster Care (VIPP-FC) is an adaptation of the evidence-based Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) and aims at increasing sensitive parenting and the use of sensitive discipline strategies of foster parents. The current study is the first to examine the effectiveness of VIPP-FC., Methods: A randomized controlled trial is used with 60 foster parent-child dyads (intervention group n = 30, control group n = 30). The primary outcomes are parental sensitivity, parental disciplining, and parental attitudes towards parenting. Data about attachment (in)security, behavioral and emotional problems, neurobiological parameters, and possible confounders is additionally collected., Discussion: Examining the effectiveness of VIPP-FC contributes to the knowledge of evidence-based prevention and intervention programs needed in foster care practice., Trial Registration: NTR3899 .

Preschoolers' vocabulary acquisition sets the stage for later reading ability and school achievement. This study examined the role of socioeconomic status (SES) and the quality of the home environment of seventy-seven Chilean majority and Mapuche minority families from low and lower-middle-class backgrounds in explaining individual differences in vocabulary acquisition of their three-and-a-half-year-old children. Additionally, we investigated whether the relation between SES and receptive and expressive vocabulary was mediated by the quality of the home environment as the Family Investment Model suggests. The quality of the home environment significantly predicted receptive and expressive vocabulary above and beyond ethnicity, SES, parental caregiver status, and quantity of daycare. Furthermore, the quality of the home environment mediated the relation between SES and expressive and receptive vocabulary acquisition.

Aims: Routinely fasting is not necessary for measuring the lipid profile according to the latest European consensus. However, LDL-C tends to be lower in the non-fasting state with risk of misclassification. The extent of misclassification in secondary cardiovascular prevention with a non-fasting lipid profile was investigated., Methods and Results: 329 patients on lipid lowering therapy for secondary cardiovascular prevention measured a fasting and non-fasting lipid profile. Cut-off values for LDL-C, non-HDL-C and apolipoprotein B were set at <1.8mmol/l, <2.6mmol/l and <0.8g/l, respectively. Study outcomes were net misclassification with non-fasting LDL-C (calculated using the Friedewald formula), direct LDL-C, non-HDL-C and apolipoprotein B. Net misclassification <10% was considered clinically irrelevant. Mean age was 68.3±8.5years and the majority were men (79%). Non-fasting measurements resulted in lower LDL-C (-0.2±0.4mmol/l, P<0.001), direct LDL-C (-0.1±0.2mmol/l, P=0.001), non-HDL-C (-0.1±0.4mmol/l, P=0.004) and apolipoprotein B (-0.02±0.10g/l, P=0.004). 36.0% of the patients reached a fasting LDL-C target of <1.8mmol/l with a significant net misclassification of 10.7% (95% CI 6.4-15.0%) in the non-fasting state. In the non-fasting state net misclassification with direct LDL-C was 5.7% (95% CI 2.1-9.2%), 4.0% (95% CI 1.0-7.4%) with non-HDL-C and 4.1% (95% CI 1.1-9.1%) with apolipoprotein B., Conclusion: Use of non-fasting LDL-C as treatment target in secondary cardiovascular prevention resulted in significant misclassification with subsequent risk of undertreatment, whereas non-fasting direct LDL-C, non-HDL-C and apolipoprotein B are reliable parameters., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This review focuses on children's physiological responses to out-of-home childcare. The finding that children's cortisol levels are higher at childcare than at home has been well-replicated. Here we summarize recent evidence examining possible correlates of elevated cortisol levels. Reviewed studies suggest that childcare quality matters, whereas group sizes and type of care do not. As for child characteristics, elevated cortisol at childcare is more pronounced in toddlers than in infants, and in inhibited and aggressive children. We discuss recent advances focusing on hair cortisol analysis and immunomarkers of stress, and suggest that there is a need for experimental and longitudinal studies to examine causal relations and possible negative long-term consequences for children's health and development., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Idiopathic retroperitoneal fibrosis (iRPF) may be a manifestation of IgG4-related disease. Measuring serum IgG4 (sIgG4) may be of value in monitoring iRPF, but this has scarcely been evaluated. It is unknown if tamoxifen (TMX) affects sIgG4 levels. We performed a prospective inception cohort study of 59 patients with untreated (re)active iRPF stratified by elevated (>1.4 g/L) or normal sIgG4 level. Changes in sIgG4 levels following TMX initiation and, if treatment failed, during subsequent corticosteroid (CS) treatment were analyzed. The median sIgG4 level was 1.1 g/L (interquartile range (IQR) 0.4-2.2); 24 patients (40%) had elevated sIgG4 level. Patients with elevated sIgG4 tended to present with higher ESR (46 vs. 34 mm/h; P = 0.08) and more frequent locoregional lymphadenopathy adjacent to the mass (41.7 vs. 20.0%; P = 0.08). sIgG4 also correlated with ESR (ρ = 0.26; P = 0.05) and serum creatinine (SC) (ρ = 0.26; P = 0.04). Following TMX initiation, sIgG4 level decreased, particularly when achieving treatment success (P < 0.01). Odds ratio for TMX treatment success in patients with elevated sIgG4 level was 0.77 (95% CI 0.53-1.14; P = 0.19). After adjusting for age, sex, and SC, the odds ratio was 0.78 (95% CI 0.51-1.18; P = 0.24). ROC curve analyses of sIgG4 on a continuous scale and treatment success showed an AUC of 0.62. Treatment success and concurrent sIgG4 decrease (P < 0.01) were achieved in 78% of patients who converted to CS therapy. Patients with elevated sIgG4 level may be more inflammatory than patients with normal sIgG4 level, but this needs further study. TMX affects sIgG4 levels, but to a lesser extent than CSs. sIgG4 cannot be used as an outcome prediction tool, irrespective of which cutoff value was chosen.

Background: Specific immunoglobulin E to Ara h 2 (sIgE to Ara h 2) is described as an upcoming predicting factor for diagnosing peanut allergy in children. The gold standard for diagnosing peanut allergy is a double blind placebo controlled food challenge, however this is time consuming and potentially harmful. We investigate Ara h 2 as a preliminary less invasive diagnostic tool for diagnosing peanut allergy in a general population of peanut sensitized children., Methods: Children (n=52) with peanut sensitization were retrospectively included. An oral food challenge (OFC) confirmed peanut allergy or tolerance, as primary outcome. Individual candidate predictors were identified by univariate regression analysis and used in a prediction model. Different cut-off values were obtained and receiver operating characteristic curves were plotted., Results: Multivariate analyses resulted in Ara h 2 as best predictor, with a discriminative ability of 0.87 (95% confidence interval, 0.77-0.97). Sensitivity and specificity of 55% and 95%, respectively, were found for a sIgE to Ara h 2 cut-off value of 4.25 kU/L. The highest positive predictive value of 100% was reached at 5.61 kU/L. No absolute relation was found between the value of Ara h 2 and the severity of the reaction during OFC., Conclusion: This study developed a prediction model in which sIgE to Ara h 2 was the best predictor for peanut allergy in sensitized children in a general hospital. Therefore depending on the history and the Ara h 2 results, an OFC is not always needed to confirm the diagnosis.

This meta-analysis reports on the effectiveness of targeted interventions focusing on child care professionals to improve child care quality, caregiver interaction skills, and child social-emotional development. Within randomized controlled trials, interventions are moderately effective in improving overall caregiver-child interactions (k = 19, Hedges' g = 0.35) and in improving child care quality on the classroom level (k = 11; Hedges' g = 0.39), the caregiver level (k = 10; Hedges' g = 0.44), and the child level (k = 6; Hedges' g = 0.26). Based on these findings, the implementation of evidence-based targeted interventions on a larger scale than currently exists may lead to better social-emotional development for children under the age of 5 years. There remains, however, an urgent need for more and larger randomized controlled trials with a solid design and high quality measures in order to shed more light on which child care components for which children are most critical in supporting children's socio-emotional development.

Background: The childcare environment offers a wide array of developmental opportunities for children. Providing children with a feeling of security to explore this environment is one of the most fundamental goals of childcare., Objective: In the current study the effectiveness of Video-feedback Intervention to promote Positive Parenting-Child Care (VIPP-CC) was tested on children's wellbeing in home-based childcare in a randomized controlled trial., Methods: Forty-seven children and their caregivers were randomly assigned to the intervention group or control group. Children's wellbeing, caregiver sensitivity, and global childcare quality were observed during a pretest and a posttest., Results: We did not find an overall intervention effect on child wellbeing, but a significant interaction effect with months spent with a trusted caregiver was present. Children who were less familiar with the caregiver showed an increase in wellbeing scores in both the intervention and control group, but for the group of children who were more familiar with the caregiver, wellbeing increased only in the intervention group., Conclusions: Although there was no overall effect of the VIPP-CC on children's wellbeing, the VIPP-CC seems effective in children who have been cared for by the same trusted caregiver for a longer period of time.

This article discusses significant changes in childcare policy and practice in Chile. We distinguish four specific periods of childcare history: child abandonment and the creation of foundling homes in the 19th century; efforts to reduce infant mortality and the creation of the health care system in the first half of the 20th century; an increasing focus on inequality and poverty and the consequences for child development in the second half of the 20th century; and, finally, the current focus on children's social and emotional development. It is concluded that, although Chile has achieved infant mortality and malnutrition rates comparable to those of developed countries, the country bears the mark of a history of inequality and is still unable to fully guarantee the health of children from the poorest sectors of society. Recent initiatives seek to improve this situation and put a strong emphasis on the psychosocial condition of children and their families.

Measurement of serum angiotensin-converting enzyme (ACE) activity can be helpful in the diagnosis and disease monitoring of sarcoidosis. Elevated serum ACE activity is found in 60-70% of sarcoidosis patients. Usually, the ACE activity is mildly increased (<3-fold the upper limit of the reference range) in sarcoidosis patients. Extremely elevated ACE activity is suggestive of the benign condition known as 'familial hyperactivity of ACE'. Familial hyperactivity of ACE is a relatively rare condition and can be confirmed by genetic testing. Considering a genetic cause of strongly elevated serum ACE activity is important to prevent possible overdiagnostics. Here, we highlight the factors that may complicate the interpretation of serum ACE activity measurements, and we present two cases that illustrate the importance of interdisciplinary consultation when extremely elevated serum ACE activity is measured.

Quantification of cortisol in scalp hair seems a promising measurement for long-term cortisol levels, and thereby a biomarker for stress. We examined hair cortisol concentrations (HCC) in children when first entering elementary school. Participants were 42 children (45% boys) with a mean age of 4.2 years (SD = 0.42 months). Hair samples (≥5 cm) were collected 2 months after school entry. Hair analysis was conducted using two 2-cm long segments, reflecting the first 2 months of school attendance (the scalp-near segment) and 2 months prior to school entry. HCC were higher after school entry than before, especially for fearful children. Alterations in HCC were not moderated by experience in group daycare before school entry. Thus, HCC suggest that starting elementary school is accompanied by increased stress hormone levels in young (in particular fearful) children.

Background: We examined whether children cared for by stressed caregivers show lower socio-emotional well-being and more stress, compared with children cared for by less stressed caregivers., Methods: Perceived stress and cortisol levels of professional caregivers (n = 44), and associations with children's (n = 44) well-being and cortisol levels in home-based child care were examined., Results: Caregiver perceived stress and cortisol levels were related to children's well-being but not to children's cortisol levels. Children's social fearfulness acted as a moderator between caregivers' mean ratio of diurnal change in cortisol and children's well-being. When caregiver cortisol levels decreased, more fearful children were reported higher on well-being than less fearful peers. In contrast, when caregiver cortisol levels increased, more fearful children were reported lower on well-being., Conclusions: The findings point to differential susceptibility. Child care organizations and parents need to notice that a non-stressful child care environment is in particular important for children with a difficult temperament., (© 2010 Blackwell Publishing Ltd.)

Does the experience of stress during child care lead to downregulation of the immune system, in particular in low-quality care? Saliva was collected from 68 toddlers attending center or family child care at home and at child care, and assayed for secretory IgA (SIgA). Caregiver sensitivity was used as an index of quality of care and was observed during three videotaped episodes of 10 min. Diurnal patterns of SIgA showed a steep fall in the morning followed by a flattening out. SIgA was not associated with type of care, but lower caregiver sensitivity was associated with lower SIgA levels in both types of care. Quality of child care is associated with a non-specific secretory component of children's mucosal immunity with well established protective effects against upper respiratory infections., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Many labs have not yet selected the most appropriate Westgard Quality Control (QC) rule for each test. This is mainly due to the apparent complexity of the matter., Methods: From the Westgard OPSpecs Charts QC planning tool and the Sigma Metrics formula's it was deduced that every Westgard rule has its own Sigma value. This was converted to an easy three-step road map to optimal Westgard QC rules., Results: The road map provided is based on Sigma Metrics that hold a definition of "world class quality", at which no further effort to increase quality needs to be taken. Furthermore, it is shown that clinical chemical tests can be classified as "good": quality at or above world class, "bad": quality below world class but controllable with Westgard QC rules and "ugly": quality not controllable with Westgard QC rules alone. Finally, practical tips of how to deal with this and related aspects are given., Conclusions: The use of the road map based on Sigma Metrics leads to fast and easy implementation of optimal Westgard QC rules.

In the present randomized controlled trial, the effectiveness of video-feedback intervention to promote positive parenting-child care (VIPP-CC) was tested in home-based child care. Forty-eight caregivers were randomly assigned either to the intervention group or to the control group. Global child care quality improved in the intervention group but not in the control group. The program did not change observed caregiver sensitivity. After the intervention however, caregivers in the intervention group reported a more positive attitude toward sensitive caregiving than caregivers in the control group. The study shows that the family-based intervention can be applied with some minor modifications in a professional group setting as well. The brief VIPP-CC program is an important tool for enhancing quality of home-based child care., (PsycINFO Database Record (c) 2011 APA, all rights reserved.)

The authors assessed the quality of child care in a representative national sample of 42 child-care centers in the Netherlands and compared it with the quality of care that researchers have found using similar samples in 1995 (M. H. van IJzendoorn, L. W. C. Tavecchio, G. J. J. M. Stams, M. J. E. Verhoeven, & E. J. Reiling, 1998) and 2001 (M. J. J. M. Gevers Deynoot-Schaub & J. M. A. Riksen-Walraven, 2005). In the present study, results showed a low level of overall process quality for the 2005 sample, measured by the Infant/Toddler Environment Rating Scale-Revised (T. Harms, D. Cryer, & R. M. Clifford, 2003) and the Early Childhood Environment Rating Scale-Revised (T. Harms, R. M. Clifford, & D. Cryer, 1998). The present authors found a significant decline in process quality in comparison with the 1995 and 2001 findings. They concluded that, from an international perspective, the Netherlands has lost its leading position in child-care quality compared with that from 10 years ago.

In this commentary to the child-mother attachment findings of the NICHD Study of Early Child Care and Youth Development (SECCYD) we focus on the contextual conditions under which child care and the child's attachment relationship(s) may function as a risk or protective factor for child development. First, the authors' conclusion concerning child care as a risk factor for attachment security is refined. Second, suggestions are provided for incorporating possible moderators and mediators of the relations between child care, child-mother attachment, and developmental outcomes. Children's attachment relationship to nonmaternal caregivers, their temperament, and their genetic make-up may be relevant factors; and we discuss them in the context of children's differential susceptibility to influences from the caregiving environment. Third, and following from the above, we argue for specificity in predicting developmental outcomes from attachment security and nonmaternal care.

The influence of interference by hemolysis, icterus and lipemia on the results of routine chemistries may lead to wrong interpretations. On Synchron LX-20 instruments (Beckman Coulter) serum or plasma indices can be used as reliable semi-quantitative measures of the magnitude of such interference. In an article recently published in this journal, we presented the results of a multicenter study carried out in Dutch hospitals in which we determined cutoff indices for analytes above which analytically significant interference exists. Clinically significant interference cutoff indices were also derived for these analytes. In this article, we describe the handling of patient samples with clinically significant interference by hemolysis, icterus or lipemia. We investigated several possible approaches for correction of the result: dilution of the interference; mathematical correction in the case of hemolysis; treatment with ferrocyanide to destroy bilirubin; and removal of lipids in lipemic patient samples. We concluded, that mathematical correction of potassium or lactate dehydrogenase results in hemolytic samples can only be carried out if intravascular hemolysis is ruled out. Hemoglobin quantification in serial patient samples, combined with measurement of haptoglobin, represents a useful tool to rule out in vivo hemolysis. We derived an algorithm for this situation. We do not simply recommend mathematical correction, unless it is clinically acceptable. We present formulas for potassium and lactate dehydrogenase: corrected potassium=measured potassium-(hemolytic index increment x 0.14); corrected lactate dehydrogenase=measured lactate dehydrogenase-(hemolytic index increment x 75). The dilution studies indicated that dilution is only applicable for bilirubin, C-reactive protein and iron. The results of treatment with ferrocyanide were poor, and we do not recommend this method. Removal of lipids using high-speed centrifugation or LipoClear (StatSpin Inc.), a non-toxic and non-ionic polymer, is a very effective approach, although C-reactive protein, creatine kinase-MB (CK-MB) and cholesterol cannot be removed using LipoClear. For all interferants (hemoglobin, bilirubin, lipids), relatively simple algorithms are derived that can easily be implemented in the clinical laboratory.

The influence of interference by hemolysis, icterus and lipemia on the results of routine chemistries may lead to wrong interpretations. The H-, I- and L-indices that can be measured by the Beckman LX-20 instrument (Beckman Coulter) in serum or plasma samples are a reliable semi-quantitative measure of the size of these interferences. A survey carried out in 16 Dutch clinical laboratories on the use of these indices demonstrated that in several of these laboratories, the influence of interferences is largely underestimated. Therefore, a multicenter study was carried out in which we examined the interference of hemolysis, icterus and lipemia on 32 analytes. On the basis of biological variation, we decided on cutoff indices above which analytically significant interference exists. We found analytically significant interference by hemolysis, icterus or lipemia, in 12, 7 and 15 of the 32 analytes studied, respectively. Flagging of results on the basis of analytically significant interference, however, results in too many clinically insignificant comments. On the basis of clinical significance, we conclude that significant interference by hemolysis, icterus or lipemia is present in only 5, 6 and 12 of the analytes studied, respectively. Use of the cutoff indices presented here facilitates optimal use of the LX-20 indices to prevent reporting of wrong results due to interference.

The objective of this study was to evaluate if D-Dimer PLUS (Dade Behring, USA), a rapid fully automated assay, could be used as an initial screening test in the diagnosis of venous thromboembolism (VTE). Samples from 274 consecutive symptomatic patients with suspected pulmonary embolism (n=229; 79% outpatients, 21% inpatients), deep venous thrombosis (n=37; 84% outpatients, 16% inpatients) or suspected for both complications (n=8) were tested with this D-dimer assay with a Sysmex CA-1500 Coagulation Analyzer. Clinical probability for pulmonary embolism (PE) or deep venous thrombosis (DVT) was staged according to a pretest risk score proposed by Wells. Final diagnosis of PE and/or DVT was established by spiral-computed tomography of the pulmonary arteries or compression ultrasonography, respectively. PE was diagnosed in 13.5% of the patients, whereas DVT was confirmed in 17.7% of the patients. The optimal cut-off value for exclusion of venous thromboembolism was 130 mug/l, and sensitivity, specificity and negative predictive value (NPV) were 95.0% (95% CI: 92.4-97.6), 30.4% (95% CI: 25.0-35.8) and 97.2% (95% CI: 95.2-99.2), respectively. In fact, two patient with PE were missed using D-Dimer PLUS; both cases were outpatients. In conclusion, this assay appears to be safe when implemented in an algorithm based on clinical assessment, D-dimer concentration, and radiological diagnostic techniques to stratify the risk for PE or DVT. However, higher sensitivities and negative predictive values were claimed in the scarce published reports for the D-Dimer PLUS assay than found in this study.

The development of the humoral anti-glycan immune response of chimpanzees, either or not vaccinated with radiation-attenuated Schistosoma mansoni cercariae, was followed during 1 year after infection with S. mansoni. During the acute phase of infection both the vaccinated and the control chimpanzees produce high levels of immunoglobulin G (IgG) antibodies against carbohydrate structures that are characteristic for schistosomes carrying the Fucalpha1-3GalNAc and Fucalpha1-2Fucalpha1-3GlcNAc motifs, but not to the more widespread occurring structures GalNAcbeta1-4GlcNAc, GalNAcbeta1-4(Fucalpha1-3)GlcNAc, and Galbeta1-4(Fucalpha1-3)GlcNAc (Lewis(x)). In addition, high levels of IgM antibodies were found against the trimeric Lewis(x) epitope. Apparently, the schistosome-characteristic carbohydrate structures are dominant epitopes in the anti-glycan humoral immune response of the chimpanzees. All chimpanzees showed an increase in the level of antibodies against most of the carbohydrate structures tested directly after vaccination, peaking at challenge time and during the acute phase of infection. With the exception of anti-F-LDN antibody responses, the anti-carbohydrate antibody responses upon schistosome infection of the vaccinated animals were muted in comparison to the control animals.

Gut-associated glycoproteins constitute a major group of the circulating excretory antigens produced by human Schistosoma species. The O-glycans of the relatively abundant circulating anodic antigen (CAA) from S. mansoni carry long stretches of unique -->6(GlcA beta 1-->3)GalNAc beta 1--> repeats. Specific anti-carbohydrate monoclonal antibodies (mAbs) are essential tools for the immunodiagnostic detection of CAA in the serum or urine of Schistosoma-infected subjects. In order to define the epitopes recognised by these anti-CAA mAbs, we screened a series of protein-coupled synthetic di- to pentasaccharide building blocks of the CAA polysaccharide for immunoreactivity, using ELISA and surface plasmon resonance spectroscopy. It was shown that anti-CAA IgM mAbs preferentially recognise -->6(GlcA beta 1-->3)GalNAc beta 1--> disaccharide units. Interestingly, no mouse anti-CAA mAbs of the IgG class were found that bind to the synthetic epitopes, although many of the IgG mAbs tested do recognise native CAA in a carbohydrate-dependent manner. In addition, both IgM and IgG class antibodies could be detected in human infection sera using the synthetic CAA fragments. These synthetic schistosome glycan epitopes and their matching set of specific mAbs are useful tools that further the development of diagnostic methods and are helpful in defining the immunological responses of the mammalian hosts to schistosome glycoconjugates.

Sponges (Porifera), the simplest and earliest multicellular organisms, are thought to have evolved from their unicellular ancestors about 1 billion years ago by developing cell-recognition and adhesion mechanisms to discriminate against "non-self." Consequently, they are used as models for investigating recognition phenomena. Cellular adhesion of marine sponges is an event involving adherence of extracellular proteoglycan-like molecules, otherwise known as aggregation factors (AFs). In a calcium-independent process the AFs adhere to the cell surface, and in a calcium-dependent process they exhibit AF self-association. A mechanism which has been implied but not definitely proven to play a role in the calcium-dependent event is self-recognition of defined carbohydrate epitopes. For the red beard sponge, Microciona prolifera, two carbohydrate epitopes, a sulfated disaccharide and a pyruvylated trisaccharide, have been implicated in cellular adhesion. To investigate this phenomenon a system has been designed, by using surface plasmon resonance detection, to mimic the role of carbohydrates in cellular adhesion of M. prolifera. The results show self-recognition of the sulfated disaccharide to be a major force behind the calcium-dependent event. The interaction is not simply based on electrostatic interactions, as other sulfated carbohydrates analyzed by using this procedure did not self-associate. Furthermore, the interaction is completely eradicated on substitution of Ca(2+) ions by either Mg(2+) or Mn(2+) ions. This physiologically relevant recognition mechanism confirms the existence of true carbohydrate self-recognition, and may have significant implications for the role of carbohydrates in cellular recognition of higher organisms.

The chemical synthesis of beta-D-GlcpA-(1-->3)-beta-D-GalpNAc-(1-->O)CH2CH = CH2, beta-D-Galp-NAc-(1-->6)-[beta-D-GlcpA-(1-->3)]-beta-D-GalpNAc-(1-- >O)CH2CH = CH2, and beta-D-GlcpA-(1-->3)-beta-D-GalpNAc-(1-->6)-[beta-D-GlcpA-(1 -->3)] -beta-D-GalpNAc-(1-->O)CH2CH = CH2 is described. These oligosaccharides represent fragments of th circulating anodic antigen, secreted by the parasite Schistosoma mansoni in the circulatory system of the host. The applied synthesis strategy includes the preparation of a non-oxidised backbone oligosaccharide, with a levulinoyl group at O-6 of the beta-D-glucose residue. After the selective removal of the levulinoyl group, the obtained hydroxyl functions were converted into carboxyl groups, using pyridinium dichromate and acetic anhydride in dichloromethane, to afford the desired glucuronic-acid-containing oligosaccharides. Subsequently, the allyl glycosides have been elongated with cysteamine to give the corresponding amine-spacer-containing oligosaccharides.