Browsing by Subject "CHILDREN"

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  • Vakkilainen, Svetlana; Taskinen, Mervi; Klemetti, Paula; Pukkala, Eero; Mäkitie, Outi (2019)
    Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia with combined immunodeficiency, variable clinical course and increased risk of malignancy. Management of CHH is complicated by a paucity of long-term follow-up data, as well as knowledge on prognostic factors. We assessed clinical course and risk factors for mortality in a prospective cohort study of 80 patients with CHH recruited in 1985-1991 and followed up until 2016. For all patients we collected additional health information from health records and from the national Medical Databases and Cause-of-death Registry. The primary outcome was immunodeficiency-related death, including death from infections, lung disease and malignancy. Standardized mortality ratios (SMRs) were calculated using national mortality rates as reference. Half of the patients (57%, n = 46) manifested no symptoms of immunodeficiency during follow-up while 19% (n = 15) and 24% (n = 19) demonstrated symptoms of humoral or combined immunodeficiency, including six cases of adult-onset immunodeficiency. In a significant proportion of patients (17/79, 22%), clinical features of immunodeficiency progressed over time. Of the 15 patients with non-skin cancer, eight had no preceding clinical symptoms of immunodeficiency. Altogether 20 patients had deceased (SMR = 7.0, 95% CI = 4.3-11); most commonly from malignancy (n = 7, SMR = 10, 95% CI = 4.1-21) and lung disease (n = 4, SMR = 46, 95% CI = 9.5-130). Mortality associated with birth length below-4 standard deviation (compared to normal, SMR/SMR ratio = 5.4, 95% CI = 1.5-20), symptoms of combined immunodeficiency (compared to asymptomatic, SMR/SMR ratio= 3.9, 95% CI = 1.3-11), Hirschsprung disease (odds ratio (OR) 7.2, 95% CI = 1.04-55), pneumonia in the first year of life or recurrently in adulthood (OR = 7.6/19, 95% CI = 1.3-43/2.6-140) and autoimmunity in adulthood (OR = 39, 95% CI = 3.5-430). In conclusion, patients with CHH may develop adult-onset immunodeficiency or malignancy without preceding clinical symptoms of immune defect, warranting careful follow-up. Variable disease course and risk factors for mortality should be acknowledged.
  • Funderud, Tonje; Mononen, Riikka; Radišić, Jelena; Laine, Anu (2019)
    The study aimed to investigate variations in addition and subtraction fluency by observing grade three students in Norway (n = 253, M-age = 8.38 y.) and Finland (n = 209, M-age = 9.35 y.) while controlling for their age and non-verbal reasoning. Gender differences were also examined. The focus of the study was on the performance of the low-achieving (LA) students in comparison to the typically achieving (TA) group, not neglecting differences in how early educational support was organised across the two countries. Two-minute speed tests in both addition and subtraction within the 1-20 number range were used to assess fluency. The Finnish students outperformed students in the Norwegian sample both in addition and subtraction fluency. There were more Norwegian students in the LA group (i.e. performance at or below the 25th percentile) in both addition (37.9% vs. 20.1%) and subtraction (39.1% vs. 15.8%). In comparison to the TA students, the LA students made more errors and skipped over more arithmetic tasks in an attempt to solve them. Observed differences are discussed in relation to both country characteristics concerning early mathematics education and early educational support.
  • Suomalainen, L.; Haravuori, H.; Berg, N.; Kiviruusu, O.; Marttunen, M. (2011)
    Background: In November 2007, a student shot eight people and himself at Jokela High School, Finland. This study aims to evaluate the long-term effects of exposure to a school shooting among adolescents. Method: Associations between psychological outcomes and background factors were analysed and compared with "comparison students" four months after the incident. A questionnaire including Impact of Event Scale (IES) and General Health Questionnaire (GHQ-36) was used. Results: Half of the females and a third of the males suffered from posttraumatic distress. High level of posttraumatic distress (IES >= 35), predicting PTSD, was observed in 27% of the females and 7% of the males. The odds ratio was 6.4 (95% confidence interval 3.5-10.5) for having high levels of posttraumatic distress. Severe or extreme exposure and female gender were found to increase the risk. Forty-two percent of the females and 16% of the males had psychiatric disturbance (GHQ >= 9). Severe or extreme exposure, older age and female gender increased the risk. Perceived support from family and friends was found to be protective. Conclusions: The observed risk and protective factors were similar to earlier studies. Follow-up will be essential in identifying factors predicting persisting trauma-related symptoms in adolescence. (C) 2010 Elsevier Masson SAS. All rights reserved.
  • Hayes, A.; Nguyen, D.; Andersson, M.; Anton, A.; Bailly, J-L; Beard, S.; Benschop, K. S. M.; Berginc, N.; Blomqvist, S.; Cunningham, E.; Davis, D.; Dembinski, J. L.; Diedrich, S.; Dudman, S. G.; Dyrdak, R.; Eltringham, G. J. A.; Gonzales-Goggia, S.; Gunson, R.; Howson-Wells, H. C.; Jääskeläinen, A. J.; Lopez-Labrador, F. X.; Maier, M.; Majumdar, M.; Midgley, S.; Mirand, A.; Morley, U.; Nordbo, S. A.; Oikarinen, S.; Osman, H.; Papa, A.; Pellegrinelli, L.; Piralla, A.; Rabella, N.; Richter, J.; Smith, M.; Strand, A. Söderlund; Templeton, K.; Vipond, B.; Vuorinen, T.; Williams, C.; Wollants, E.; Zakikhany, K.; Fischer, T. K.; Harvala, H.; Simmonds, P. (2020)
    Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 mu L) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 mu L) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 x 10(-5)). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
  • Li, Dong; Chang, Xiao; Connolly, John J.; Tian, Lifeng; Liu, Yichuan; Bhoj, Elizabeth J.; Robinson, Nora; Abrams, Debra; Li, Yun R.; Bradfield, Jonathan P.; Kim, Cecilia E.; Li, Jin; Wang, Fengxiang; Snyder, James; Lemma, Maria; Hou, Cuiping; Wei, Zhi; Guo, Yiran; Qiu, Haijun; Mentch, Frank D.; Thomas, Kelly A.; Chiavacci, Rosetta M.; Cone, Roger; Li, Bingshan; Sleiman, Patrick A.; Hakonarson, Hakon; Eating Disorders Working Group of the Psychiatric Genomics Consortium; Kaprio, Jaakko; Palotie, Aarno; Raevuori-Helkamaa, Anu; Ripatti, Samuli; Price Fdn Collaborative Grp (2017)
    We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.
  • Poller, Bettina; Strachan, Clare; Broadbent, Roland; Walker, Greg F. (2017)
    The purpose of this study was to evaluate electrospun drug loaded nanofibers as a new matrix for mini tablets. Prednisone, a poorly water-soluble drug, was loaded into povidone (polyvinylpyrrolidone, PVP) nanofibers using the process of electrospinning. The drug-loaded nanofiber mat was compressed into minitablets with a 2 mm diameter and a height of 2.63 0.04 mm. SEM analysis of the minitablet identified a nano-web structure with a nanofiber diameter in the range of 400-500 nm. The minitablets met the requirements of the US Pharmacopeia with respect to content uniformity and friability. DSC and XRPD analysis of the minitablet indicated that the drug-polymer mixture was a one-phase amorphous system. XRPD analysis of the drug loaded nanofiber mat after 10-months of storage at ambient temperature showed no evidence of recrystallization of the drug. Solubility and dissolution properties of the drug formulated into a nanofiber mat and minitablet were evaluated. These results show that electrospun nanofibers may provide a useful matrix for the further development of minitablets. (C) 2017 Elsevier B.V. All rights reserved.
  • Roininen, Saara; Laine, Outi; Kauppila, Marjut; Vesanen, Marko; Ramet, Maria; Sinisalo, Marjatta; Jantunen, Esa; Saily, Marjaana; Räty, Riikka; Elonen, Erkki; Wartiovaara-Kautto, Ulla (2017)
    Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000. In the risk factor analyses for VTs we found a distinction of the characteristics of the patients acquiring CVT from those with other kinds of VTs or without thrombosis. In contrast to previous studies we were also able to compare the effects of asparaginase in relation to CVT occurrence. Notably, more than half of the CVTs were diagnosed prior the administration of asparaginase which accentuates the role of other risk factors on the pathophysiology of CVT compared to truncal or central venous line (CVL) VTs in adult ALL patients.
  • Tudor-Locke, Catrine; Mire, Emily F.; Dentro, Kara N.; Barreira, Tiago V.; Schuna, John M.; Zhao, Pei; Tremblay, Mark S.; Standage, Martyn; Sarmiento, Olga L.; Onywera, Vincent; Olds, Tim; Matsudo, Victor; Maia, Jose; Maher, Carol; Lambert, Estelle V.; Kurpad, Anura; Kuriyan, Rebecca; Hu, Gang; Fogelholm, Mikael; Chaput, Jean-Philippe; Church, Timothy S.; Katzmarzyk, Peter T.; Grp, I. S. C. O. L. E. Res (2015)
    Background: We present a model for reporting accelerometer paradata (process-related data produced from survey administration) collected in the International Study of Childhood Obesity Lifestyle and the Environment (ISCOLE), a multi-national investigation of >7000 children (averaging 10.5 years of age) sampled from 12 different developed and developing countries and five continents. Methods: ISCOLE employed a 24-hr waist worn 7-day protocol using the ActiGraph GT3X+. Checklists, flow charts, and systematic data queries documented accelerometer paradata from enrollment to data collection and treatment. Paradata included counts of consented and eligible participants, accelerometers distributed for initial and additional monitoring (site specific decisions in the face of initial monitoring failure), inadequate data (e.g., lost/malfunction, insufficient wear time), and averages for waking wear time, valid days of data, participants with valid data (>= 4 valid days of data, including 1 weekend day), and minutes with implausibly high values (>= 20,000 activity counts/min). Results: Of 7806 consented participants, 7372 were deemed eligible to participate, 7314 accelerometers were distributed for initial monitoring and another 106 for additional monitoring. 414 accelerometer data files were inadequate (primarily due to insufficient wear time). Only 29 accelerometers were lost during the implementation of ISCOLE worldwide. The final locked data file consisted of 6553 participant files (90.0% relative to number of participants who completed monitoring) with valid waking wear time, averaging 6.5 valid days and 888.4 minutes/day (14.8 hours). We documented 4762 minutes with implausibly high activity count values from 695 unique participants (9.4% of eligible participants and Conclusions: Detailed accelerometer paradata is useful for standardizing communication, facilitating study management, improving the representative qualities of surveys, tracking study endpoint attainment, comparing studies, and ultimately anticipating and controlling costs.
  • Sofou, Kalliopi; De Coo, Irenaeus F. M.; Isohanni, Pirjo; Ostergaard, Elsebet; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; De Angst, Isabell B.; Lonnqvist, Tuula; Pihko, Helena; Mankinen, Katariina; Bindoff, Laurence A.; Tulinius, Mar; Darin, Niklas (2014)
  • Kort, Remco; Westerik, Nieke; Serrano, L. Mariela; Douillard, Francois P.; Gottstein, Willi; Mukisa, Ivan M.; Tuijn, Coosje J.; Basten, Lisa; Hafkamp, Bert; Meijer, Wilco C.; Teusink, Bas; de Vos, Willem M.; Reid, Gregor; Sybesma, Wilbert (2015)
    Background: The lactic acid bacterium Lactobacillus rhamnosus GG is the most studied probiotic bacterium with proven health benefits upon oral intake, including the alleviation of diarrhea. The mission of the Yoba for Life foundation is to provide impoverished communities in Africa increased access to Lactobacillus rhamnosus GG under the name Lactobacillus rhamnosus yoba 2012, world's first generic probiotic strain. We have been able to overcome the strain's limitations to grow in food matrices like milk, by formulating a dried starter consortium with Streptococcus thermophilus that enables the propagation of both strains in milk and other food matrices. The affordable seed culture is used by people in resource-poor communities. Results: We used S. thermophilus C106 as an adjuvant culture for the propagation of L. rhamnosus yoba 2012 in a variety of fermented foods up to concentrations, because of its endogenous proteolytic activity, ability to degrade lactose and other synergistic effects. Subsequently, L. rhamnosus could reach final titers of 1E+09 CFU ml(-1), which is sufficient to comply with the recommended daily dose for probiotics. The specific metabolic interactions between the two strains were derived from the full genome sequences of L. rhamnosus GG and S. thermophilus C106. The piliation of the L. rhamnosus yoba 2012, required for epithelial adhesion and inflammatory signaling in the human host, was stable during growth in milk for two rounds of fermentation. Sachets prepared with the two strains, yoba 2012 and C106, retained viability for at least 2 years. Conclusions: A stable dried seed culture has been developed which facilitates local and low-cost production of a wide range of fermented foods that subsequently act as delivery vehicles for beneficial bacteria to communities in east Africa.
  • Kroger, Liisa; Löppönen, Tuija; Ala-Kokko, Leena; Kröger, Heikki; Jauhonen, Hanna-Mari; Lehti, Kaisa; Jaaskelainen, Jarmo (2019)
    Background MONA, which stands for a spectrum of Multicentric Osteolysis, subcutaneous Nodulosis, and Athropathia, is an ultra rare autosomal recessive disorder caused by mutations in the matrix metallopeptidase 2 (MMP2) gene. To date only 44 individuals, carrying 22 different mutations have been reported. Here we report on two brothers with identical homozygous MMP2 gene mutations, but with clearly different phenotypes. Methods Genomic DNA was isolated from the affected brothers and the parents. An iliac crest bone biopsy was taken from the younger patient (index case). The level of matrix metallopeptidase 2 enzyme (MMP2) in serum and synovial fluid of the younger patient was analyzed using gelatin zymography. Results The DNA analysis revealed a homozygous c.1188C>A transversion on exon 8 of the gene. The affected brothers had the same homozygous variant and the parents were heterozygous to this variant. This variant has been reported as a compound heterozygous mutation on one individual resulting in scleroderma like skin thickening. Bone histomorphometry indicated increased trabecular bone remodeling and turnover. The zymography revealed that the level of MMP2 was completely nonmeasurable in the serum and only a minor gelatinolytic protein band of about similar molecular weight as MMP2 was found in the synovial fluid. Conclusions Both the age at the onset and the phenotypic severity of the syndrome in these two brothers were different despite identical genotypes. The younger patients had corneal opacities leading to deteriorating visual acuity. For the first time in this disease, opacities were successfully treated with corneal transplantations.
  • Hannula, Leena; Puukka, Pauli; Asunmaa, Marjut; Mäkijärvi, Markku (2020)
    Background Many infants under 4 months suffer from infantile colic. Infants with colic cry a lot, appear to be in pain, and it is difficult to sooth them. Colic is a painful condition for the infant and very stressful to parents. Parents in Finland get advice to try reflexology treatment for their infant, but there are no studies in Finland to support this advice. Aim The aim of the pilot study was to treat infants with reflexology and find out parents' experiences of the effects of the treatment on colic symptoms and parental stress. Method A total of 33 parents of 35 infants diagnosed with colic participated to the pilot study. Three certified reflexologists with health care education background and extensive experience in infant reflexology were trained to give the reflexology treatment in a standardised manner. They treated each infant 3-4 times. The whole body reflexology treatment session consisted of gentle pressure treatment of soles and feet, hands, head, face, ears, back, neck and whole stomach area. One treatment session lasted about 20-30 minutes, and treatments were delivered within 8-12 days. The data were collected from the parents with semi-structured questionnaires. Results The series of the treatments helped reduce the suffering of all the babies with infant colic. The colic symptoms disappeared on 43% of infants and decreased on the remaining 57%. The parents reported having pleasant experiences with the treatment, regardless whether the colic symptoms disappeared or continued. Parents stated that the treatment reduced the most typical colic symptoms; infants' body tension, colic crying and restless movements, poor sleep quality and irregular bowel movements. Conclusions Reflexology treatment seems to be a safe and effective way to treat infants with colic when conducted by a health care professional with reflexology training and experience.
  • Einarsdottir, Elisabet; Pekkinen, Minna; Krjutskov, Kaarel; Katayama, Shintaro; Kere, Juha; Mäkitie, Outi; Viljakainen, Heli (2019)
    Objective: The effect of vitamin D at the transcriptome level is poorly understood, and furthermore, it is unclear if it differs between obese and normal-weight subjects. The objective of the study was to explore the transcriptome effects of vitamin D supplementation. Design and methods: We analysed peripheral blood gene expression using GlobinLock oligonucleotides followed by RNA sequencing in individuals participating in a 12-week randomised double-blinded placebo-controlled vitamin D intervention study. The study involved 18 obese and 18 normal-weight subjects (of which 20 males) with mean (+/- s.D.) age 20.4 (+/- 2.5) years and BMIs 36 (+/- 10) and 23 (+/- 4) kg/m(2), respectively. The supplemental daily vitamin D dose was 50 mu g (2000 IU). Data were available at baseline, 6- and 12-week time points and comparisons were performed between the vitamin D and placebo groups separately in obese and normal-weight subjects. Results: Significant transcriptomic changes were observed at 6 weeks, and only in the obese subjects: 1724 genes were significantly upregulated and 186 genes were downregulated in the vitamin D group compared with placebo. Further analyses showed several enriched gene categories connected to mitochondrial function and metabolism, and the most significantly enriched pathway was related to oxidative phosphorylation (adjusted P value 3.08 x 10(-14)). Taken together, our data suggest an effect of vitamin D supplementation on mitochondrial function in obese subjects. Conclusions: Vitamin D supplementation affects gene expression in obese, but not in normal-weight subjects. The altered genes are enriched in pathways related to mitochondrial function. The present study increases the understanding of the effects of vitamin D at the transcriptome level.
  • Dagan, Ron; Ben-Shimol, Shalom; Simell, Birgit; Greenberg, David; Porat, Nurith; Käyhty, Helena; Givon-Lavi, Noga (2018)
    Background: We compared PCV7 serological response and protection against carriage in infants receiving 3 doses (2, 4, 6 months; 3+0 schedule) to those receiving a booster (12 months; 3+1). Methods: A prospective, randomized controlled study, conducted between 2005 and 2008, before PCVs were implemented in Israel. Healthy infants were randomized 1:1:1 to receive 3+1, 3+0 and 0+2 (control group; 12, 18 months doses). Nasopharyngeal/oropharyngeal swabs were obtained at all visits. Serum serotype-specific IgG concentrations and opsonic activities (OPA) were measured at 2, 7, 13 and 19 months. This study was registered with Current Controlled Trials, Ltd. ISRCTN28445844. Results: Overall, 544 infants were enrolled: 3+1 (n = 178), 3+0 (n = 178) and 0+2 (n = 188). Post-priming (7 months), antibody concentrations were similar in both groups, except for serotype 18C (higher in 3+0). Post-booster (13, 19 months), ELISA and OPA levels were significantly higher in 3+1 than in 3+0 group. Nasopharyngeal/oropharyngeal cultures were positive for Streptococcus pneumoniae in 2673 (543%) visits. Acquisition rates (vaccine and non-vaccine serotypes) were similar for 3+1 and 3+0 groups at 7-30 months and for 0+2 group at 19-30 months. Conclusions: PCV7 booster after 3 priming doses increased substantially IgG concentrations but did not further reduced vaccine-serotype nasopharyngeal acquisition, suggesting that protection from pneumococcal carriage does not depend primarily on serum IgG. (C) 2018 Elsevier Ltd. All rights reserved.
  • Carlsson, Annelie; Shepherd, Maggie; Ellard, Sian; Weedon, Michael; Lernmark, Ake; Forsander, Gun; Colclough, Kevin; Brahimi, Qefsere; Valtonen-Andre, Camilla; Ivarsson, Sten A.; Elding Larsson, Helena; Samuelsson, Ulf; Ortqvist, Eva; Groop, Leif; Ludvigsson, Johnny; Marcus, Claude; Hattersley, Andrew T. (2020)
    OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population. RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1-18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCK, HNF1A, and HNF4A, through either routine clinical or research testing. RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 x 10(-44)), HbA(1c) (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 x 10(-20)), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 x 10(-19)), parental diabetes (63% vs. 12%; P = 1 x 10(-15)), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA(1c)
  • Putkuri, Niina; Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli (2016)
    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001-2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross neutralization tests confirmed presence of INKV or CHATV infections. All children (
  • Simola, Umberto; Cisewski-Kehe, Jessi; Gutmann, Michael U.; Corander, Jukka (2021)
    Approximate Bayesian Computation (ABC) methods are increasingly used for inference in situations in which the likelihood function is either computationally costly or intractable to evaluate. Extensions of the basic ABC rejection algorithm have improved the computational efficiency of the procedure and broadened its applicability. The ABC - Population Monte Carlo (ABC-PMC) approach has become a popular choice for approximate sampling from the posterior. ABC-PMC is a sequential sampler with an iteratively decreasing value of the tolerance, which specifies how close the simulated data need to be to the real data for acceptance. We propose a method for adaptively selecting a sequence of tolerances that improves the computational efficiency of the algorithm over other common techniques. In addition we define a stopping rule as a by-product of the adaptation procedure, which assists in automating termination of sampling. The proposed automatic ABC-PMC algorithm can be easily implemented and we present several examples demonstrating its benefits in terms of computational efficiency.
  • Blaser, Cornelia; Klein, Matthias; Grandgirard, Denis; Wittwer, Matthias; Peltola, Heikki; Weigand, Michael; Koedel, Uwe; Leib, Stephen L. (2010)
  • Udden, Fabian; Filipe, Matuba; Reimer, Ake; Paul, Maria; Matuschek, Erika; Thegerstrom, John; Hammerschmidt, Sven; Pelkonen, Tuula; Riesbeck, Kristian (2018)
    Background: Chronic suppurative otitis media (CSOM) is an important cause of hearing loss in children and constitutes a serious health problem globally with a strong association to resource-limited living conditions. Topical antibiotics combined with aural toilet is the first-hand treatment for CSOM but antimicrobial resistance and limited availability to antibiotics are obstacles in some areas. The goal of this study was to define aerobic pathogens associated with CSOM in Angola with the overall aim to provide a background for local treatment recommendations. Methods: Samples from ear discharge and the nasopharynx were collected and cultured from 152 patients with ear discharge and perforation of the tympanic membrane. Identification of bacterial species was performed with matrix-assisted laser desorption/ionization-time of flight mass spectrometry and pneumococci were serotyped using multiplex polymerase chain reactions. Antimicrobial susceptibility testing was done according to EUCAST. Results: One hundred eighty-four samples from ear discharge and 151 nasopharyngeal swabs were collected and yielded 534 and 289 individual isolates, respectively. In all patients, correspondence rate of isolates from 2 ears in patients with bilateral disease was 27.3% and 9.3% comparing isolates from the nasopharynx and ear discharge, respectively. Proteus spp. (14.7%), Pseudomonas aeruginosa (13.2%) and Enterococcus spp. (8.8%) were dominating pathogens isolated from ear discharge. A large part of the remaining species belonged to Enterobacteriaceoe (23.5%). Pneumococci and Staphylococcus aureus were detected in approximately 10% of nasopharyngeal samples. Resistance rates to quinolones exceeded 10% among Enterobacterioceae and was 30.8% in S. aureus, whereas 6.3% of P. aeruginosa were resistant. Conclusions: The infection of the middle ear in CSOM is highly polymicrobial, and isolates found in nasopharynx do not correspond well with those found in ear discharge. Pathogens associated with CSOM in Angola are dominated by gram-negatives including Enterobacteriaceoe and P. aeruginosa, while gram-positive enterococci also are common. Based on the results of antimicrobial susceptibility testing topical quinolones would be the preferred antibiotic therapy of CSOM in Angola. Topical antiseptics such as aluminium acetate, acetic acid or boric acid, however, may be more feasible options due to a possibly emerging antimicrobial resistance.
  • Bauer, Witold; Veijola, Riitta; Lempainen, Johanna; Kiviniemi, Minna; Härkönen, Taina; Toppari, Jorma; Knip, Mikael; Gyenesei, Attila; Ilonen, Jorma (2019)
    Context: Children with initial autoantibodies to either insulin (IAA) or glutamic acid decarboxylase (GADA) differ in peak age of seroconversion and have different type 1 diabetes (T1D) risk gene associations, suggesting heterogeneity in the disease process. Objective: To compare the associations of age at seroconversion, HLA risk, and specificity of secondary autoantibodies with the progression of islet autoimmunity between children with either IAA or GADA as their first autoantibody. Design and methods: A cohort of 15,253 children with HLA-associated increased risk of T1D participated in a follow-up program in which islet autoantibodies were regularly measured. The median follow-up time was 6.7 years. Spearman correlation, Kaplan-Meier survival plots, and Cox proportional-hazard models were used for statistical analyses. Results: Persistent positivity for at least one of the tested autoantibodies was detected in 998 children; 388 of children progressed to clinical T1D. Young age at initial seroconversion was associated with a high probability of expansion of IAA-initiated autoimmunity and progression to clinical diabetes, whereas expansion of GADA-initiated autoimmunity and progression to diabetes were not dependent on initial seroconversion age. The strength of HLA risk affected the progression of both IAA- and GADA-initiated autoimmunity. The simultaneous appearance of two other autoantibodies increased the rate of progression to diabetes compared with that of a single secondary autoantibody among subjects with GADA-initiated autoimmunity but not among those with IAA as the first autoantibody. Conclusions: Findings emphasize the differences in the course of islet autoimmunity initiated by either IAA or GADA supporting heterogeneity in the pathogenic process.