Direct Observation of Sub-Poissonian Temporal Statistics in a Continuous Free-Electron Beam with Subpicosecond Resolution.

We present a novel method to measure the arrival time statistics of continuous electron beams with subpicosecond resolution, based on the combination of an rf deflection cavity and fast single electron imaging. We observe Poissonian statistics within time bins from 100 to 2 ns and increasingly pronounced sub-Poissonian statistics as the time bin decreases from 2 ps to 340 fs. This 2D streak camera, in principle, enables femtosecond-level arrival time measurements, paving the way to observing Pauli blocking effects in electron beams and thus serving as an essential diagnostic tool toward degenerate electron beam sources for free-electron quantum optics.

AI-support for the detection of intracranial large vessel occlusions: One-year prospective evaluation.

Purpose: Few studies have evaluated real-world performance of radiological AI-tools in clinical practice. Over one-year, we prospectively evaluated the use of AI software to support the detection of intracranial large vessel occlusions (LVO) on CT angiography (CTA). Method: Quantitative measures (user log-in attempts, AI standalone performance) and qualitative data (user surveys) were reviewed by a key-user group at three timepoints. A total of 491 CTA studies of 460 patients were included for analysis. Results: The overall accuracy of the AI-tool for LVO detection and localization was 87.6%, sensitivity 69.1% and specificity 91.2%. Out of 81 LVOs, 31 of 34 (91%) M1 occlusions were detected correctly, 19 of 38 (50%) M2 occlusions, and 6 of 9 (67%) ICA occlusions. The product was considered user-friendly. The diagnostic confidence of the users for LVO detection remained the same over the year. The last measured net promotor score was -56%. The use of the AI-tool fluctuated over the year with a declining trend. Conclusions: Our pragmatic approach of evaluating the AI-tool used in clinical practice, helped us to monitor the usage, to estimate the perceived added value by the users of the AI-tool, and to make an informed decision about the continuation of the use of the AI-tool.

Parental support and insecure attachment development: the cortisol stress response as a moderator.

The current study investigated whether variations at the level of the cortisol stress response moderate the association between parental support and attachment development. To test this hypothesis, we conducted a one-year longitudinal study with two waves in which 101 children (56% girls, Mage = 11.15, SDage = 0.70) participated. Attachment anxiety and avoidance were measured at baseline (Wave 1) and one year later (Wave 2). Parental support and children's cortisol stress response during the Trier Social Stress Test were measured at Wave 2. Children's cortisol stress response was found to moderate the association between parental support and relative change in anxious attachment. A strong cortisol stress response weakened the associated between parental support and relative change in anxious attachment. No moderation effects were found for relative change in avoidant attachment.

'Implementing a broad quality of life tool for determining care wishes and needs of older adults living at home.

The aim was to investigate the views of stakeholders on the practical relevance of a broad quality of life (QoL) outcome tool for care in older adults: the Extended Quality of Life Tool (EQLT). We conducted individual interviews and focus groups with a variety of stakeholders involved in the care for older adults which were analyzed using a framework analysis. Stakeholders considered relevant: focus on the client perspective; perspective on QoL broader than health; the possibility to take diversity into account; and the possibility to determine a minimum level of QoL. Three facilitators for implementation of the tool were mentioned as well as four barriers. The EQLT can support conversations with clients about their needs and wishes, thus enabling decisions about care services based on a broad set of domains of QoL. Implementation of the tool should take into account the facilitators and barriers identified in the current study.

Predictors and consequences of non-suicidal self-injury in relation to life, peer, and school factors.

INTRODUCTION: Numerous life, peer, and school-related factors have been found to be associated with non-suicidal self-injury (NSSI) among adolescents; however, most studies have not explored the possible reciprocal nature of these associations. The aim of the current study was to examine bidirectional and longitudinal associations between NSSI and several life, peer, and school-related factors (i.e., stressful life events, peer relationships, academic achievement, and attitudes towards school). METHOD: Community-based adolescents completed questionnaires assessing the variables of interest at three time points; age 12 (T1; 55.09% girls), age 13 (T2; 56.95% girls), and ages 14-15 (T3; 57.41% girls). In total, 529 adolescents provided complete data across all three-time points. RESULTS: Analyses showed a bidirectional association between NSSI and both attitudes towards school and stressful life events. Specifically, stressful life events at T2 predicted engagement in NSSI at T3, and NSSI at T2 predicted increased risk of stressful life events at T3. Similarly, having negative attitudes towards school predicted NSSI at T2, which, in turn, predicted negative attitudes towards school at T3. Further, academic achievement at T1 was negatively associated with NSSI at T2. Peer relationships were neither a predictor nor a consequence of NSSI. CONCLUSIONS: Our results suggest that NSSI can be both a predictor and a consequence of various life, and school factors. Focus on these factors in prevention and intervention efforts for NSSI among adolescents may be warranted.

Alpha-1-antitrypsin deficiency (carrier) as possible risk factor for development of colonic diverticula. A multicentre prospective case-control study: the ALADDIN study.

AIM: Connective tissue changes due to ageing or diseases leading to changes in the colonic wall are one theory for the development of diverticula. Alpha-1-antitrypsin (A1AT), a protease inhibitor that protects connective tissue, possibly plays a role in the aetiology of diverticulosis. The aim of this study was to explore associations between the development of diverticula and A1AT deficiency. METHODS: This was a multicentre prospective case-control study. A total of 221 patients aged ≥ 60 years with acute abdominal pain undergoing abdominal CT were included and analysed. Patients with diverticula were defined as the research group, patients without diverticula as controls. Genotype analysis for A1AT deficiency was performed. RESULTS: Twenty-six of 221 (11.8%) patients were diagnosed with (being a carrier of) A1AT deficiency. A non-significant difference in prevalence between patients with and without diverticula was found, 20 (13.9%) of 144 vs 6 (7.8%) of 77, respectively, with a crude OR of 1.9 (95% CI 0.7-5.0; P = 0.186) and after adjustment for confounders an adjusted OR of 1.5 (95% CI 0.5-4.0; P = 0.466). A non-significant difference in 30-day mortality rate from acute diverticulitis between A1AT deficient patients (or carriers) and those without was observed: two (22.2%) of nine patients with A1AT deficiency vs 1 (1.8%) of 55 without. CONCLUSION: We found no convincing evidence that A1AT deficiency plays a role in the aetiology of diverticulitis, although deficient patients and carriers had a higher mortality when experiencing diverticulitis. Diverticulitis is a multifactorial disease and larger numbers may be needed to explore the role of A1AT deficiency among other contributing factors.

Parenting, Effortful Control, and Adolescents' Externalizing Problem Behavior: Moderation by Dopaminergic Genes.

Research shows that genetics and effortful control play an important role in the link between parenting and problem behavior. However, little is known about how these factors act simultaneously. This article used a moderated mediation model to examine whether effortful control mediated the link between parenting and externalizing problem behavior, and whether dopaminergic genes (i.e., polygenic index score including DAT1, DRD2, DRD4, COMT) moderated this link. Two three-wave studies were conducted on community samples (adolescents: Study 1: N = 457; Mage = 15.74; Study 2: N = 221; Mage = 12.84). There was no mediation by effortful control, but a moderation by dopaminergic reactivity was observed. Despite inconsistent evidence, this article indicates that the development of externalizing problem behavior is subject to genetic characteristics and parenting.

Complex medical history of a patient with a compound heterozygous mutation in C1QC.

INTRODUCTION: C1q is an essential part of the classical pathway of complement activation. Genetic deficiencies, caused by homozygous mutations in one of the C1q genes, are rare and are strongly associated with development of systemic lupus erythematosus (SLE). Here we describe a C1q-deficient patient with a compound heterozygous mutation. MATERIAL AND METHODS: Serum was analysed with enzyme-linked immunosorbent assay (ELISA) and Western blot for the presence of C1q, and DNA and RNA sequencing was performed to identify the mutations and confirm that these were located on different chromosomes. RESULTS: The medical history of the patient includes SLE diagnosis at age 11 years with cerebral involvement at age 13, various infections, osteonecrosis and hemophagocytic syndrome. Using ELISA and Western blot, we confirmed the absence of C1q in the serum of the patient. Using DNA sequencing, two mutations in the C1QC gene were identified: c.100G > A p.(Gly34Arg) and c.205C > T p.(Arg69X). With RNA sequencing we confirmed that the mutations are located on different chromosomes. DISCUSSION: The patient described in this case report has a compound heterozygous mutation in C1QC resulting in C1q deficiency.

Enhancing cardiovascular artificial intelligence (AI) research in the Netherlands: CVON-AI consortium.

BACKGROUND: Machine learning (ML) allows the exploration and progressive improvement of very complex high-dimensional data patterns that can be utilised to optimise specific classification and prediction tasks, outperforming traditional statistical approaches. An enormous acceleration of ready-to-use tools and artificial intelligence (AI) applications, shaped by the emergence, refinement, and application of powerful ML algorithms in several areas of knowledge, is ongoing. Although such progress has begun to permeate the medical sciences and clinical medicine, implementation in cardiovascular medicine and research is still in its infancy. OBJECTIVES: To lay out the theoretical framework, purpose, and structure of a novel AI consortium. METHODS: We have established a new Dutch research consortium, the CVON-AI, supported by the Netherlands Heart Foundation, to catalyse and facilitate the development and utilisation of AI solutions for existing and emerging cardiovascular research initiatives and to raise AI awareness in the cardiovascular research community. CVON-AI will connect to previously established CVON consortia and apply a cloud-based AI platform to supplement their planned traditional data-analysis approach. RESULTS: A pilot experiment on the CVON-AI cloud was conducted using cardiac magnetic resonance data. It demonstrated the feasibility of the platform and documented excellent correlation between AI-generated ventricular function estimates as compared to expert manual annotations. The resulting AI solution was then integrated in a web application. CONCLUSION: CVON-AI is a new consortium meant to facilitate the implementation and raise awareness of AI in cardiovascular research in the Netherlands. CVON-AI will create an accessible cloud-based platform for cardiovascular researchers, demonstrate the clinical applicability of AI, optimise the analytical methodology of other ongoing CVON consortia, and promote AI awareness through education and training.

Detecting abnormal electroencephalograms using deep convolutional networks.

OBJECTIVES: Electroencephalography (EEG) is a central part of the medical evaluation for patients with neurological disorders. Training an algorithm to label the EEG normal vs abnormal seems challenging, because of EEG heterogeneity and dependence of contextual factors, including age and sleep stage. Our objectives were to validate prior work on an independent data set suggesting that deep learning methods can discriminate between normal vs abnormal EEGs, to understand whether age and sleep stage information can improve discrimination, and to understand what factors lead to errors. METHODS: We train a deep convolutional neural network on a heterogeneous set of 8522 routine EEGs from the Massachusetts General Hospital. We explore several strategies for optimizing model performance, including accounting for age and sleep stage. RESULTS: The area under the receiver operating characteristic curve (AUC) on an independent test set (n = 851) is 0.917 marginally improved by including age (AUC = 0.924), and both age and sleep stages (AUC = 0.925), though not statistically significant. CONCLUSIONS: The model architecture generalizes well to an independent dataset. Adding age and sleep stage to the model does not significantly improve performance. SIGNIFICANCE: Insights learned from misclassified examples, and minimal improvement by adding sleep stage and age suggest fruitful directions for further research.

Quality of life in a broader perspective: Does ASCOT reflect the capability approach?

PURPOSE: Economic evaluation of services and interventions in care services tends to focus on quality of life(QoL) based on health-related measures such as EQ5D, with a major focus on health and functioning. The Capability Approach (CA) provides an alternative framework for measuring QoL and challenges some of the conventional issues in the current practice of measurement of QoL. The Adult Social Care Outcomes Toolkit (ASCOT) aims to measure social care-related QoL in a broad sense. This article investigates whether and, if so, how the ASCOT addresses issues put on the agenda by the CA. METHODS: Literature analysis concerning theoretical assumptions and arguments of CA and ASCOT. RESULTS: The Capability Approach (CA) puts three issues on the agenda regarding QoL. First, the focus of evaluation should not be on functioning, but on freedom of choice. Second, evaluation should be critical about adaptive preferences, which entail that people lower expectations in situations of limited possibilities. Third, evaluation should not only address health, but also other domains of life. Our analysis shows that freedom of choice is reflected in the response option 'as I want' in the ASCOT questionnaire. The problem of adaptive preferences is countered in the ASCOT by developing a standard based on preferences of the general population. Third, the ASCOT contains several domains of life. CONCLUSIONS: We conclude that the CA and the ASCOT contribute to the discussion on QoL, and that the ASCOT operationalizes core assumptions of the CA, translating the issues raised by the CA in a practical way.

Adapting SimpleTreat for simulating behaviour of chemical substances during industrial sewage treatment.

The multimedia model SimpleTreat, evaluates the distribution and elimination of chemicals by municipal sewage treatment plants (STP). It is applied in the framework of REACH (Registration, Evaluation, Authorization and Restriction of Chemicals). This article describes an adaptation of this model for application to industrial sewage treatment plants (I-STP). The intended use of this re-parametrized model is focused on risk assessment during manufacture and subsequent uses of chemicals, also in the framework of REACH. The results of an inquiry on the operational characteristics of industrial sewage treatment installations were used to re-parameterize the model. It appeared that one property of industrial sewage, i.e. Biological Oxygen Demand (BOD) in combination with one parameter of the activated sludge process, the hydraulic retention time (HRT) is satisfactory to define treatment of industrial wastewater by means of the activated sludge process. The adapted model was compared to the original municipal version, SimpleTreat 4.0, by means of a sensitivity analysis. The consistency of the model output was assessed by computing the emission to water from an I-STP of a set of fictitious chemicals. This set of chemicals exhibit a range of physico-chemical and biodegradability properties occurring in industrial wastewater. Predicted removal rates of a chemical from raw sewage are higher in industrial than in municipal STPs. The latter have typically shorter hydraulic retention times with diminished opportunity for elimination of the chemical due to volatilization and biodegradation.

Depressive symptoms in adolescence: The role of perceived parental support, psychological control, and proactive control in interaction with 5-HTTLPR.

BACKGROUND: Parenting dimensions are associated with depressive symptoms in adolescents. We investigated the role of perceived parenting dimensions and gene-environment interactions between these perceived parenting dimensions and five well-known variable number of tandem repeats (VNTRs): 5-HTTLPR, STin2, DAT1, DRD4, and MAO-A, in depressive symptoms. METHODS: From a non-clinical sample of 1111 Belgian adolescents (mean age: 13.79 years, SD=.94; 51% boys), 1103 adolescents consented for genetic research. Five VNTRs were analyzed using DNA from saliva samples. Perceived parenting dimensions (i.e., support, proactive control, psychological control, punishment, and harsh punishment) were examined using self-report scales completed by adolescents and their parents. Depressive symptoms were investigated using the CES-D self-report scale. Statistical analyses were performed in R using linear regression. RESULTS: Parental support, as perceived by the adolescent, was negatively associated with depressive symptoms (CES-D) and psychological control was positively associated with these symptoms. The only interaction effect withstanding correction for multiple testing was observed for 5-HTTLPR and the difference in proactive control as perceived by adolescents in comparison to parents. Short-allele carriers showed more depressive symptoms when there was a higher discrepancy in proactive control as perceived by adolescents versus parents. CONCLUSIONS: Our results suggest that perceived parenting dimensions are associated with depressive symptoms, as measured by the CES-D. We only found modest evidence for 5-HTTLPR as a moderator in the association between the difference in perception of proactive control (adolescents vs. parents) and depressive symptoms.

Higher body mass index is associated with plantar fasciopathy/'plantar fasciitis': systematic review and meta-analysis of various clinical and imaging risk factors.

QUESTION: What (risk) factors are associated with plantar fasciopathy (PF)? DESIGN: Systematic review with meta-analyses. PARTICIPANTS: Patients with PF. FACTORS: All factors described in prospective, case-control or cross-sectional observational studies. RESULTS: 51 included studies (1 prospective, 46 case-control and 4 cross-sectional studies) evaluated a total of 104 variables. Pooling was possible for 12 variables. Higher body mass index (BMI) (BMI>27, OR 3.7 (95% CI 2.93 to 5.62)) in patients with PF was the only significant clinical association, and its effect was the strongest in the non-athletic subgroup. In people with PF compared to controls, pooled imaging data demonstrated a significantly thicker, hypoechogenic plantar fascia with increased vascular signal and perifascial fluid collection. In addition, people with PF were more likely to have a thicker loaded and unloaded heel fat pat, and bone findings, including a subcalcaneal spur and increased Tc-99 uptake. No significant difference was found in the extension of the first metatarsophalangeal joint. CONCLUSIONS: We found a consistent clinical association between higher BMI and plantar fasciopathy. This association may differ between athletic and non-athletic subgroups. While consistent evidence supports a range of bone and soft tissue abnormalities, there is lack of evidence for the dogma of clinical and mechanical measures of foot and ankle function. Clinicians can use this information in shared decision-making.

Study on the protective effect of the KIR3DL1 gene in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is an autoimmune disease that mainly affects the sacroiliac joints and the spine of the lower back. The disease is strongly associated with HLA-B27. Additional genes, single-nucleotide polymorphisms, and molecular components have been identified to be associated with AS, but the exact mechanism that drives disease development remains poorly understood. The killer cell immunoglobulin-like receptors (KIRs) are regulators of cytotoxicity of natural killer cells and T cell subsets and may be relevant in binding to HLA-B27 and the development of AS. We undertook this study to identify possible associations of KIR genotype with susceptibility to AS and disease characteristics including the presence of the HLA-B27 allele, disease severity, and uveitis. METHODS: We performed complete genotyping of the KIR locus in 303 Caucasian AS patients, 119 randomly selected healthy Caucasian controls, and 50 HLA-B27-positive healthy Caucasian controls by multiplex ligation-dependent probe amplification assay for detection of gene presence and copy number. RESULTS: We did not observe a significant association of any specific KIR gene or haplotype with susceptibility to AS or any other clinical manifestation. Disease severity, as measured by fulfilling the criteria for treatment with tumor necrosis factor blocking therapy, was linked to a lower number of genes for the functional variant of KIR3DL1 (P = 0.007). CONCLUSION: Our exploratory study indicates that KIR genes are not a major risk factor for susceptibility to AS. However, the data do suggest a role for KIRs in progression of the disease, whereby KIR3DL1 has a protective effect against the more severe manifestations of AS.

Novel insights in the genomic organization and hotspots of recombination in the human KIR locus through analysis of intergenic regions.

The Killer Immunoglobulin-like Receptor (KIR) proteins constitute a family of highly homologous surface receptors involved in the regulation of the innate cytotoxicity of natural killer (NK) cells. Within the human genome, 17 KIR genes are present, many of which show large variation across the population owing to the high number of allelic variants and copy number variation (CNV). KIR genotyping and CNV determination were used to map the KIR locus in a large cohort of >400 Caucasian individuals. Gene order and structure was determined by sequence-specific polymerase chain reaction of the intergenic regions. In this way, we could show that KIR3DL1 and KIR2DS4 gene variants are linked and that--contrary to current views--the gene KIR2DS5 is only present in the telomeric half of the KIR locus. Our study revealed novel insights in the highly organized distribution of KIR genes. Novel recombination hotspots were identified that contribute to the diversity of KIR gene distribution in the Caucasian population. Next-generation sequencing of the KIR intergenic regions allowed for a detailed single-nucleotide polymorphism analysis, which demonstrated several gene-specific as well as haplotype-specific nucleotides for a more accurate genotyping of this notoriously complex gene cluster.

What can local authorities do to improve the social care-related quality of life of older adults living at home? Evidence from the Adult Social Care Survey.

Local authorities spend considerable resources on social care at home for older adults. Given the expected growth in the population of older adults and budget cuts on local government, it is important to find efficient ways of maintaining and improving the quality of life of older adults. The ageing in place literature suggests that policies in other functions of local authorities may have a significant role to play. This study aims to examine the associations between social care-related quality of life (SCRQoL) in older adults and three potential policy targets for local authorities: (i) accessibility of information and advice, (ii) design of the home and (iii) accessibility of the local area. We used cross-sectional data from the English national Adult Social Care Survey (ASCS) 2010/2011 on service users aged 65 years and older and living at home (N=29,935). To examine the association between SCRQoL, as measured by the ASCOT, and three single-item questions about accessibility of information, design of the home and accessibility of the local area, we estimate linear and quantile regression models. After adjusting for physical and mental health factors and other confounders our findings indicate that SCRQoL is significantly lower for older adults who find it more difficult to find information and advice, for those who report that their home design is inappropriate for their needs and for those who find it more difficult to get around their local area. In addition, these three variables are as strongly associated with SCRQoL as physical and mental health factors. We conclude that in seeking to find ways to maintain and improve the quality of life of social care users living at home, local authorities could look more broadly across their responsibilities. Further research is required to explore the cost-effectiveness of these options compared to standard social care services.

Four different NCF2 mutations in six families from Turkey and an overview of NCF2 gene mutations.

BACKGROUND: One of the rarest forms of autosomal recessive chronic granulomatous disease (AR-CGD) is attributable to mutations in the NCF2 gene, which encodes the polypeptide p67(phox), a key cytoplasmic protein in the phagocyte NADPH oxidase system. NCF2 is localized on chromosome 1q25, encompasses 40 kb and contains 16 exons. MATERIALS AND METHODS: We report here the clinical and molecular characterization of six patients with CGD from six consanguineous Turkish families. The ages of the five female patients were between 3 and 22 years and a male patient was 2 years old; all patients showed clear clinical symptoms of CGD. RESULTS: The mothers of the patients did not show a bimodal histogram pattern specific for X-CGD in the dihydrorhodamine-1,2,3 (DHR) assay. Moreover, p67(phox) protein expression was not detectable using flow cytometric analysis of the patients' neutrophils except in those from patient 6, which had a diminished expression. Mutation analysis of NCF2 revealed four different homozygous mutations: a novel nonsense mutation in exon 3 c.229C>T, p.Arg77X; a novel missense mutation in exon 4 c.279C>G, p.Asp93Glu; a nonsense mutation in exon 4 c.304C>T, p.Arg102X; and a novel missense mutation in exon 6 c.605C>T, p.Ala202Val. The parents were found to be heterozygotes for these mutations. CONCLUSIONS: The prevalence of NCF2 mutant families is approximately 15% in our series of 40 CGD families. This high incidence of A67 CGD in Turkey is undoubtedly caused by the high incidence of consanguineous marriages. We found three new mutations in NCF2 and one previously described. These are presented together with an overview of all NCF2 mutations now known.

Using chemical categories to fill data gaps in hazard assessment.

Hazard assessments of chemicals have been limited by the availability of test data and the time needed to evaluate the test data. While available data may be inadequate for the majority of industrial chemicals, the body of existing knowledge for most hazards is large enough to permit reliable estimates to be made for untested chemicals without additional animal testing. We provide a summary of the growing use by regulatory agencies of the chemical categories approach, which groups chemicals based on their similar toxicological behaviour and fills in the data gaps in animal test data such as genotoxicity and aquatic toxicity. Although the categories approach may be distinguished from the use of quantitative structure-activity relationships (QSARs) for specific hazard endpoints, robust chemical categories are founded on quantifying the chemical structure with parameters that control chemical behaviour in conventional hazard assessment. The dissemination of the QSAR Application Toolbox by the Organisation for Economic Cooperation and Development (OECD) is an effort to facilitate the use of the categories approach and reduce the need for additional animal testing.

Six different CYBA mutations including three novel mutations in ten families from Turkey, resulting in autosomal recessive chronic granulomatous disease.

BACKGROUND: One of the rarest forms of autosomal recessive chronic granulomatous disease (AR-CGD) is attributable to mutations in the CYBA gene, which encodes the alpha polypeptide of cytochrome b(558), (also known as p22-phox), a key transmembrane protein in the phagocyte NADPH oxidase system. This gene is localized on chromosome 16q24, encompasses 8.5 kb and contains six exons. MATERIALS AND METHODS: We report here the clinical and molecular characterization of 12 AR-CGD patients from 10 consanguineous, unrelated Turkish families with clinical CGD and positive family history. The ages of the six male and six female patients were between 1and 18 years. Before mutation analysis, subgroup analysis of patients was made by flow cytometry with antibodies against NADPH-oxidase components and with the DHR assay (flow cytometric assay of NADPH oxidase activity in leucocytes). RESULTS: Mutation analysis of CYBA showed six different mutations: a frameshift insertion in exon 3 (C after C166); a missense mutation in exon 2 (p.Gly24Arg), a splice-site deletion in intron 1 (4-bp deletion +4_+7 AGTG), a novel nonsense mutation in exon 6 (p.Cys113X), a novel large deletion of exons 3-6 and a novel 1-bp deletion in exon 6 (c.408delC). All mutations were present in homozygous form and all parents investigated were found to be heterozygotes for these mutations. CONCLUSIONS: In our series of 40 CGD families, approximately 25% of the families have p22-phox defects, with six different mutations, including three novel mutations. The high rate of consanguineous marriages seems to be the underlying aetiology.