Form removal aspects on the waviness parameters for steel sheet in automotive applications : fourier filtering versus polynomial regression

Premium car makers attach great importance to the visual appearance of the painted car skin as an indication of product quality. The “orange peel” phenomenon constitutes a major problem here. It is not only depending on the paint’s chemical composition and application method, but also on possible waviness components in the sheet substrate. Therefore one is searching hard for a valuable waviness parameter to quantify the substrate’s fitness for purpose. A technically emerging problem is how to remove the form from the measured signal, which is indeed not significant to the orange peel phenomenon. This paper will compare two commonly used approaches: i.e. Fourier filtering versus polynomial regression and will reveal and quantify some common aspects in terms of wavelengths

Effectiveness of analgesic ear drops as add-on treatment to oral analgesics in children with acute otitis media: study protocol of the OPTIMA pragmatic randomised controlled trial

INTRODUCTION: Ear pain is the most prominent symptom of childhood acute otitis media (AOM). To control the pain and reduce reliance on antibiotics, evidence of effectiveness for alternative interventions is urgently needed. This trial aims to investigate whether analgesic ear drops added to usual care provide superior ear pain relief over usual care alone in children presenting to primary care with AOM. METHODS AND ANALYSIS: This is a pragmatic, two-arm, individually randomised, open, superiority trial with cost-effectiveness analysis and nested mixed-methods process evaluation in general practices in the Netherlands. We aim to recruit 300 children aged 1–6 years with a general practitioner (GP) diagnosis of AOM and ear pain. Children will be randomly allocated (ratio 1:1) to either (1) lidocaine hydrochloride 5 mg/g ear drops (Otalgan) one to two drops up to six times daily for a maximum of 7 days in addition to usual care (oral analgesics, with/without antibiotics); or (2) usual care. Parents will complete a symptom diary for 4 weeks as well as generic and disease-specific quality of life questionnaires at baseline and 4 weeks. The primary outcome is the parent-reported ear pain score (0–10) over the first 3 days. Secondary outcomes include proportion of children consuming antibiotics, oral analgesic use and overall symptom burden in the first 7 days; number of days with ear pain, number of GP reconsultations and subsequent antibiotic prescribing, adverse events, complications of AOM and cost-effectiveness during 4-week follow-up; generic and disease-specific quality of life at 4 weeks; parents’ and GPs’ views and experiences with treatment acceptability, usability and satisfaction. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee Utrecht, the Netherlands, has approved the protocol (21-447/G-D). All parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings. TRIAL REGISTRATION: The Netherlands Trial Register: NL9500; date of registration: 28 May 2021. At the time of publication of the study protocol paper, we were unable to make any amendments to the trial registration record in the Netherlands Trial Register. The addition of a data sharing plan was required to adhere to the International Committee of Medical Journal Editors guidelines. The trial was therefore reregistered in ClinicalTrials.gov (NCT05651633; date of registration: 15 December 2022). This second registration is for modification purposes only and the Netherlands Trial Register record (NL9500) should be regarded as the primary trial registration

Impact of Repeated Influenza Immunization on Respiratory Illness in Children With Preexisting Medical Conditions

PURPOSE Annual influenza immunization in medical risk groups is recommended in many countries. Recent evidence suggests that repeated inactivated influenza vaccine (IIV) immunization throughout childhood may impair long-term immunity against influenza. We assessed whether prior immunization altered the effect of IIV in children with preexisting medical conditions on primary care–diagnosed respiratory illness (RI) episodes during the influenza season. METHODS Electronic records of IIV-immunized children who met the criteria for annual IIV immunization according to Dutch guidelines were extracted from a primary care database from 2004 to 2015. For each year, we collected information on IIV immunization status, primary care–attended RI episodes (including influenza-like illness, acute RI, and asthma exacerbation), and potential confounders. Generalized estimating equations were used to model the association between prior IIV and occurrence of at least one RI episode during the influenza season, with “current year immunized but without IIV history” as reference group. RESULTS A total of 4,183 children (follow-up duration: 11,493 child-years) were IIV immunized at least once. Adjusted estimates showed lower odds for RI in current year–immunized children with prior IIV compared with those without (odds ratio [OR] = 0.61; 95% CI, 0.47-0.78 for “current year immunized and one IIV in previous 2 years”; OR = 0.85; 95% CI, 0.68-1.07 for “current year immunized and ≥2 IIVs in previous 3 years, including prior year”). CONCLUSION Repeated IIV immunization in children with preexisting medical conditions has no negative impact on, and may even increase, long-term protection against RI episodes diagnosed during the influenza season in primary care

Topical or oral antibiotics for children with acute otitis media presenting with ear discharge: study protocol of a randomised controlled non-inferiority trial

BACKGROUND: Around 15%-20% of children with acute otitis media present with ear discharge due to a spontaneous tear or perforation of the eardrum (AOMd). Current guidance recommends clinicians to consider oral antibiotics as first-line treatment in this condition. The opening in the eardrum however should allow topical antibiotics to enter the middle ear directly. Local administration of antibiotics does not expose children to systemic side effects and may put less selective resistance pressure on bacteria. Evidence on the effectiveness of this approach in children with AOMd is lacking. METHODS AND ANALYSIS: A primary care-based, open, individually randomised, controlled, non-inferiority trial. The trial aims to recruit 350 children aged 6 months to 12 years with AOMd and ear pain and/or fever. Participants will be randomised to 7 days of hydrocortisone-bacitracin-colistin eardrops five drops three times daily or amoxicillin oral suspension 50 mg/kg body weight per day, divided over three doses. Parents will keep a daily diary of AOM symptoms, adverse events and complications for 2 weeks. In addition, they will record AOM recurrences, healthcare utilisation and societal costs for 3 months. The primary outcome is the proportion of children without ear pain and fever at day 3. Secondary outcomes include ear pain and fever intensity/severity; days with ear discharge; eardrum perforation at 2 weeks; adverse events during first 2 weeks; costs; and cost effectiveness at 2 weeks and 3 months. The primary analyses will be intention-to-treat and per-protocol analyses will be conducted as well. ETHICS AND DISSEMINATION: The medical research ethics committee Utrecht, The Netherlands has given ethical approval (17-400/G-M). Parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings. TRIAL REGISTRATION NUMBER: The Netherlands National Trial Register; NTR6723. Date of registration: 27 November 2017

Meningokokkenziekte in Nederland : Achtergrondinformatie voor de Gezondheidsraad

Meningococcal disease is a very serious infectious disease caused by a bacterium, the meningococcus. There are different types of meningococcus; people become ill mainly from the B, C, W and Y serogroups. Since 2002, vaccination against serogroup C meningococcal disease has been included in the National Immunisation Programme for children of 14 months. As a result, serogroup C meningococcal disease has virtually disappeared. Vaccines against serogroup B have recently become available. In addition, since 2015, there has been a rapid increase in serogroup W meningococcal disease. Multi-component vaccines are available against A, C, W and Y serogroups. Based on these developments, among others, the Health Council will advise the Minister for Health, Welfare and Sport on whether and how the current immunisation programme against meningococcal disease should be adapted. To this end, RIVM has collected background information and recent data on meningococcal disease in the Netherlands. It includes the number of people in the Netherlands who become ill each year, the efficacy and safety of the vaccines, and what the public thinks about vaccination against invasive meningococcal disease. The infection causes a severe medical condition such as meningitis or blood poisoning, which can rapidly develop into shock, frequently causing death. The disease often begins with flu-like symptoms and fever which subsequently worsen very rapidly. The infection is relatively rare in the Netherlands; there are currently 100 to 150 patients a year. Five to ten percent of these patients die despite antibiotics and intensive care. Thirty percent of the patients are left with lifelong impairments such as hearing loss, limb amputation or epilepsy. Meningococcal disease is most common in children under the age of 5, adolescents and the elderly.Meningokokkenziekte is een zeer ernstige infectieziekte die veroorzaakt wordt door een bacterie, de meningokok. Er zijn verschillende typen meningokokken; mensen worden vooral ziek van de serogroepen B, C, W en Y. Vaccinatie tegen meningokokkenziekte serogroep C is in Nederland sinds 2002 opgenomen in het Rijksvaccinatieprogramma voor kinderen van 14 maanden. Hierdoor komt meningokokkenziekte door serogroep C nauwelijks meer voor. Sinds kort zijn vaccins beschikbaar tegen serogroep B. Daarnaast is er sinds 2015 een snelle toename in meningokokkenziekte door serogroep W. Er zijn combinatievaccins beschikbaar tegen serogroep A, C, W en Y. Vanwege ondermeer deze ontwikkelingen gaat de Gezondheidsraad de minister van VWS adviseren of, en op welke manier, het huidige vaccinatieprogramma tegen meningokokkenziekte aangepast moet worden. Daartoe heeft het RIVM achtergrondinformatie en recente data over meningokokkenziekte in Nederland verzameld. Het gaat onder meer om het aantal mensen in Nederland dat jaarlijks ziek wordt, de effectiviteit en veiligheid van de vaccins, en hoe het publiek denkt over vaccinatie tegen invasieve meningokokkenziekte. De infectie geeft een ernstig ziektebeeld zoals hersenvliesontsteking of een bloedvergiftiging, die zich snel kan ontwikkelen tot een shock waar veel mensen aan overlijden. De ziekte begint vaak met griepachtige verschijnselen en koorts die vervolgens zeer snel verergeren. De infectie is in Nederland relatief zeldzaam; op dit moment zijn er 100 tot 150 patiënten per jaar. Van deze patiënten overlijdt 5-10 procent ondanks antibiotica en intensieve zorg. 30 procent van de patiënten houdt er levenslang beperkingen aan over zoals gehoorverlies, amputatie van een ledemaat of epilepsie. Meningokokkenziekte komt het meest voor bij kinderen jonger dan 5 jaar, adolescenten en ouderenMinisterie van VW

A prediction model for underestimation of invasive breast cancer after a biopsy diagnosis of ductal carcinoma in situ: based on 2892 biopsies and 589 invasive cancers

Background: Patients with a biopsy diagnosis of ductal carcinoma in situ (DCIS) might be diagnosed with invasive breast cancer at excision, a phenomenon known as underestimation. Patients with DCIS are treated based on the risk of underestimation or progression to invasive cancer. The aim of our study was to expand the knowledge on underestimation and to develop a prediction model. Methods: Population-based data were retrieved from the Dutch Pathology Registry and the Netherlands Cancer Registry for DCIS between January 2011 and June 2012. Results: Of 2892 DCIS biopsies, 21% were underestimated invasive breast cancers. In multivariable analysis, risk factors were high-grade DCIS (odds ratio (OR) 1.43, 95% confidence interval (CI): 1.05–1.95), a palpable tumour (OR 2.22, 95% CI: 1.76–2.81), a BI-RADS (Breast Imaging Reporting and Data System) score 5 (OR 2.36, 95% CI: 1.80–3.09) and a suspected invasive component at biopsy (OR 3.84, 95% CI: 2.69–5.46). The predicted risk for underestimation ranged from 9.5 to 80.2%, with a median of 14.7%. Of the 596 invasive cancers, 39% had unfavourable features. Conclusions: The risk for an underestimated diagnosis of invasive breast cancer after a biopsy diagnosis of DCIS is considerable. With our prediction model, the individual risk of underestimation can be calculated based on routinely available preoperatively known risk factors (https://www.evidencio.com/models/show/1074)

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Background: Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods: The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings: 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; p<0·0001). Of 2844 patients in the entire cohort, the main clinical syndromes were pneumonia (511 [18·0%] patients), CNS infection (469 [16·5%]), and skin and soft tissue infection (247 [8·7%]). The causal microorganism was identified in 1359 (47·8%) children, with the most prevalent ones being Neisseria meningitidis (in 259 [9·1%] patients), followed by Staphylococcus aureus (in 222 [7·8%]), Streptococcus pneumoniae (in 219 [7·7%]), and group A streptococcus (in 162 [5·7%]). 1070 (37·6%) patients required admission to a paediatric intensive care unit. Of 2469 patients with outcome data, 57 (2·2%) deaths occurred: seven were in patients with severe focal infections and 50 in those with sepsis. Interpretation: Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients