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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Thermally activated surface diffusion has a strong influence on structure widths in atom lithography. We investigate the effects of two barriers to thermally activated atomic diffusion on atom lithography: a thermally activated Ehrlich–Schwoebel (ES) barrier, and pollution from the residual gas in the vacuum system. We performed kinetic Monte Carlo simulations using a one-dimensional surface grid. We find that the ES barrier fails to explain the lack of temperature dependence observed experimentally [W. R. Anderson et al., Phys. Rev. A 59, 2476 (1999)]. The dependencies of the structure width on temperature, vacuum conditions, and beam characteristics can be explained using the pollutant adatom hypothesis. Only the variation of structure width with deposition duration was not entirely reproduced by this model. We attribute this to the one-dimensional nature of our simulations. These results demonstrate that barrier-limited diffusion can play an important role in atom lithography, and that pollutant adatoms are a likely candidate barrier. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Using direct-write atom lithography, Fe nanolines are deposited with a pitch of 186 nm, a full width at half maximum (FWHM) of 50 nm, and a height of up to 6 nm. These values are achieved by relying on geometrical collimation of the atomic beam, thus without using laser collimation techniques. This opens the way for applying direct-write atom lithography to a wide variety of elements. [ABSTRACT FROM AUTHOR]

Background and Aims: The aim of this study was to determine the cause of taints and off-flavours in a number of commercial wines and to develop methods for quantitative analysis of the compounds responsible. Methods and Results: Three compounds, 2-chloro-6-methylphenol (i.e. 6-chloro- ortho-cresol), 2,6-dichlorophenol and indole, were identified by gas chromatography (GC)/mass spectrometry (MS)/olfactometry as causes of taints or off-flavours in the wines. New methods for quantitative analysis of these three compounds, as well as some other chloro- and bromophenols were developed. The methods employed GC/MS and stable isotope dilution analysis, and confirmed the presence of 2-chloro-6-methylphenol, 2,6-dichlorophenol and indole in some wines at concentrations well above their odour and taste detection thresholds. Conclusions: 2-Chloro-6-methylphenol, 2,6-dichlorophenol and indole were confirmed as causes of taints and off-flavours in commercial wines. Significance of the Study: The development of new analytical methods will make it possible to determine whether chlorophenol (and perhaps also bromophenol) taint in wine is more widespread than previously recognised. Similarly, the simple, rapid and accurate method for quantifying indole in wine will allow large numbers of wine and ferment samples to be studied to determine those factors that can result in unacceptably high concentrations in commercial wines. [ABSTRACT FROM AUTHOR]

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 p67phox, 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, p67phox 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. [ABSTRACT FROM AUTHOR]

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 b558, (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We describe in detail a method that permits determination to an accuracy of 5% or better of the absolute amplitude of a microwave electric field inside a resonant cavity. The method is based on an analysis of the frequency dependence of sampled-power measurements that record the response not only of the cavity but also of the waveguide circuit to which it is connected. Even small reflections from real, nonideal waveguide components lead to a frequency-dependent interference pattern that extends over a much wider range in frequency than does the sharp, resonant response of the cavity. The microwave cavity is modeled with an equivalent circuit model, and the interference pattern in the waveguide circuit is modeled in much the same way as is a Fabry–Pérot interferometer. From this one may obtain accurate values for the Q factor of the cavity resonance and the coupling factor that quantifies how well the cavity is matched to the rest of the waveguide circuit. We also discuss a method to determine accurately the power absorbed by the cavity, using the same waveguide circuit. We confirm the accuracy of the method by comparing to a microwave field-amplitude-dependent physical process, which can be calculated from first principles. [ABSTRACT FROM AUTHOR]

Direct write atom lithography is a technique in which nearly resonant light is used to pattern an atom beam. Nanostructures are formed when the patterned beam falls onto a substrate. We have applied this lithography scheme to a ferromagnetic element, using a 372 nm laser light standing wave to pattern a beam of iron atoms. In this proof-of-principle experiment, we have deposited a grid of 50-nm-wide lines 186 nm apart. These ultraregular, large-scale, ferromagnetic wire arrays may generate exciting new developments in the fields of spintronics and nanomagnetics. [ABSTRACT FROM AUTHOR]

In order to provide a legal framework within the European Union (EU)for the evaluation of existing chemicals (i.e., substances listed inthe European Inventory of Existing Commercial Substances), Council Regulation (EEC) 793/93 was adopted, in which the evaluation of the existing chemicals is carried out by four steps, namely data collection, priority setting, risk assessment, and, if necessary, risk reduction. To fulfill the priority-setting step the EU Risk Ranking Method (EURAM) was developed to produce rankings that are the basis for drawing up lists of substances, used for priority setting, among the so-called high production volume chemicals appearing in the International Uniform Chemical Information database. The EURAM ranks substances on the basis of their potential risk to humans and the environment by using a simple exposure-effect model, containing both human health and environmental effect endpoints as well as exposure parameters. The EURAM fulfills criteria for a good chemical ranking scheme and has been applied and used as a basis for selecting substances for the second and the third list of priority substances as foreseen under Council Regulation (EEC) 793/93. [ABSTRACT FROM AUTHOR]