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- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 7. |
- Johansson, Jonas, et al.
(author)
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Solar disinfection at low costs: an experimental approach towards up-scaled continuous flow systems
- 2022
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In: H2open Journal. - : IWA Publishing. - 2616-6518. ; 5:1, s. 153-165
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Journal article (peer-reviewed)abstract
- SOlar DISinfection (SODIS) systems have been studied with the aim of maintaining pathogen removal efficiencies and low costs. Such systems are useful for quickly improving the situation of more than 700 million people worldwide that lack access to an improved water source. Currently, SODIS is mainly used with PET-bottles that are exposed to UV-A radiation for 6 h in the sun. Up-scaled continuous flow SODIS systems could instead provide a continuous source of drinking water, whereas the use of plastic tubes, easily available on local markets, ensures a low construction cost of the systems. Such tubes (PVC) were tested and the best option showed a UV-A transparency ratio of similar to 50%, to be compared with similar to 60% for PET-bottles. By using static batches in samples of this tube, the residence time was investigated and the results show that E. coli concentrations of 0 CFU/ml are reached within less than 4 h of exposure to solar radiation, starting from an initial concentration of 10(6) CFU/ml. It can be concluded that cheap, easily available plastic tubes can be used for treating contaminated water with the SODIS technique, which is promising for future investigations towards constructing continuous flow SODIS systems at low costs.
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| 8. |
- Runeson, B., et al.
(author)
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Instruments for the assessment of suicide risk: A systematic review evaluating the certainty of the evidence
- 2017
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
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Research review (peer-reviewed)abstract
- Background Instruments have been developed to facilitate suicide risk assessment. We aimed to evaluate the evidence for these instruments including assessment of risk of bias and diagnostic accuracy for suicide and suicide attempt. Methods PubMed (NLM), PsycInfo, Embase, Cinahl and the Cochrane Library databases were searched until December 2014. We assessed risk of bias with QUADAS-2. The average sensitivity and specificity of each instrument was estimated and the certainty of the evidence was assessed with GRADE. We considered instruments with a sensitivity > 80% and a specificity > 50% to have sufficient diagnostic accuracy. Results Thirty-five relevant studies were identified but 14 were considered to have high risk of bias, leaving 21 studies evaluating altogether 15 risk assessment instruments. We could carry out meta-analyses for five instruments. For the outcome suicide attempt SAD PERSONS Scale had a sensitivity of 15% (95% CI 8-24) and specificity of 97% (96-98), and the Manchester Self-Harm Rule (MSHR) a sensitivity of 97% (97-97) and a specificity of 20% (20-21). ReACT, which is a modification of MSHR, had a similar low specificity, as did the Sodersjukhuset Self Harm Rule. For the outcome suicide, the Beck Hopelessness Scale had a sensitivity of 89% (78-95) and specificity of 42% (40-43). Conclusions Most suicide risk assessment instruments were supported by too few studies to allow for evaluation of accuracy. Among those that could be evaluated, none fulfilled requirements for sufficient diagnostic accuracy.
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- Adamson, Carly, et al.
(author)
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Efficacy of Dapagliflozin in Heart Failure with Reduced Ejection Fraction According to Body Mass Index.
- 2021
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In: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:10, s. 1662-1672
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Journal article (peer-reviewed)abstract
- AIMS: In heart failure with reduced ejection fraction (HFrEF), there is an ’obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium-glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse- outcomes in Heart Failure trial (DAPA-HF). METHODS AND RESULTS: Body mass index was examined using standard categories, i.e. underweight ($<$18.5 kg/m(2) ); normal weight (18.5-24.9 kg/m(2) ); overweight (25.0-29.9 kg/m(2) ); obesity class I (30.0-34.9 kg/m(2) ); obesity class II (35.0-39.9 kg/m(2) ); and obesity class III ($>$/=40 kg/m(2) ). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal- weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16-1.71), overweight 1.18 (0.97-1.42), obesity class II/III 1.37 (1.10-1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58-0.94), overweight 0.81 (0.65-1.02), obesity class I 0.68 (0.50-0.92), obesity class II/III 0.71 (0.51-1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7-1.1) kg (P $<$ 0.001). CONCLUSION: We confirmed an ’obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.
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| 11. |
- Adamsson, Carl, et al.
(author)
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Modeling and Validation of a Mechanistic Tool (MEFISTO) for the Prediction of Critical Power in BWR Fuel Assemblies
- 2011
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In: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 241:8, s. 2843-2858
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Journal article (peer-reviewed)abstract
- Westinghouse is currently developing the MEFISTO code with the main goal to achieve fast, robust, practical and reliable prediction of steady-state dryout Critical Power in Boiling Water Reactor (BWR) fuel bundle based on a mechanistic approach. A computationally efficient simulation scheme was used to achieve this goal, where the code resolves all relevant field (drop, steam and multi-film) mass balance equations, within the annular flow region, at the sub-channel level while relying on a fast and robust two-phase (liquid/steam) sub-channel solution to provide the cross-flow information. The MEFISTO code can hence provide highly detailed solution of the multi-film flow in BWR fuel bundle while enhancing flexibility and reducing the computer time by an order of magnitude as compared to a standard three-field sub-channel analysis approach. Models for the numerical computation of the one-dimensional field flowrate distributions in an open channel (e.g. a sub-channel), including the numerical treatment of field cross-flows, part-length rods, spacers grids and post-dryout conditions are presented in this paper. The MEFISTO code is then applied to dryout prediction in BWR fuel bundle using VIPRE-W as a fast and robust two-phase sub-channel driver code. The dryout power is numerically predicted by iterating on the bundle power so that the minimum film flowrate in the bundle reaches the dryout criteria. Predicted dryout powers (including trends with flow, pressure, inlet subcooling and power distribution) and predicted dryout locations (both axial and radial) are compared to experimental results, using the entire Westinghouse SVEA-96 Optima3 dryout database, and are shown to yield excellent results.
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| 12. |
- Alarcon, Sonia, et al.
(author)
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Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2 ',3,4,4 ',5,5 '-heptachlorobiphenyl (PCB 180) : A postnatal follow-up study in rats
- 2021
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In: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 102, s. 109-127
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Journal article (peer-reviewed)abstract
- PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions.
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- Holmgren, Jan, 1944, et al.
(author)
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Mucosal adjuvants and anti-infection and anti-immunopathology vaccines based on cholera toxin, cholera toxin B subunit and CpG DNA
- 2005
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In: Immunology Letters. - : Elsevier. - 0165-2478 .- 1879-0542. ; 97:2, s. 181-8
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Journal article (peer-reviewed)abstract
- Mucosal immunisation may be used both to protect the mucosal surfaces against infections and as a means for immunological treatment of peripheral immunopathological disorders through the induction of systemic antigen-specific tolerance ('oral tolerance'). The development of mucosal vaccines, whether for prevention of infectious diseases or for oral tolerance immunotherapy, requires efficient antigen delivery and adjuvant systems that can help to present the appropriate vaccine or immunotherapy antigens to the mucosal immune system. The most potent (but also toxic) mucosal adjuvants are cholera toxin (CT) and the closely related Escherichia coli heat-labile enterotoxin (LT), and much effort and significant progress have been made recently to generate toxicologically acceptable derivatives of these toxins with retained adjuvant activity. Among these are the non-toxic, recombinantly produced cholera toxin B-subunit (CTB). CTB is a specific protective antigen component of a widely registered oral cholera vaccine as well as a promising vector for either giving rise to mucosal anti-infective immunity or for inducing peripheral anti-inflammatory tolerance to chemically or genetically linked foreign antigens administered mucosally. CT and CTB have also recently been used as combined vectors and adjuvants for markedly promoting ex vivo dendritic cell (DC) vaccination with different antigens and also steering the immune response to the in vivo-reinfused DCs towards either broad Th1 + Th2 + CTL immunity (CT) or Th2 or tolerance (CTB). Another type of mucosal adjuvants is represented by bacterial DNA or synthetic oligodeoxynucleotides containing CpG-motifs, which especially when linked to CTB have been found to effectively stimulate both innate and adaptive mucosal immune responses. The properties and clinical potential of these different classes of adjuvants are being discussed. © 2004 Elsevier B.V. All rights reserved.
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- Landström, Fredrik J., 1966-, et al.
(author)
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Electroporation therapy for T1 and T2 oral tongue cancer
- 2011
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In: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 131:6, s. 660-664
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Journal article (peer-reviewed)abstract
- Conclusion: Electroporation therapy appears to be a safe treatment achieving excellent local tumor control and very good functional results in our study and it should be further clinically evaluated.Objectives: The objectives of this study were to assess local tumor control, survival, and effects on speech and eating after treatment of tongue cancer with electroporation therapy, a new local therapeutic modality. In this approach intracellular accumulation of a chemotherapeutic agent is achieved by using a locally applied electrical field.Methods: Fifteen patients with primary T1 and T2 oral tongue cancer were treated with electroporation therapy with intratumorally administered bleomycin. Postoperative radiotherapy was performed when the tumor infiltration was 5 mm or more. The follow-up time was 24 months for the surviving patients and 20.4 months overall. The effects on eating and speech were assessed using the PSS-HN scale and voice recordings.Results: No local recurrence was recorded in any patient during the follow-up. Three patients died, two from progressive regional disease. Of the 12 surviving patients, 2 patients had regional recurrence and 10 patients including the 5 patients treated with EPT alone were tumor-free both locally and regionally at the last follow-up. The functional outcome for speech and eating were very good.
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| 17. |
- Landström, Fredrik J, et al.
(author)
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Electroporation therapy of skin cancer in the head and neck area.
- 2010
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In: Dermatologic Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1076-0512 .- 1524-4725. ; 36:8, s. 1245-50
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Journal article (peer-reviewed)abstract
- BACKGROUND: Electroporation therapy is a new cancer treatment modality in which a locally applied electrical field enhances cell membrane permeability, allowing greater intracellular accumulation of a chemotherapeutic agent.OBJECTIVE: To evaluate the efficacy of electroporation therapy in treating basal cell and squamous cell carcinomas of the skin.MATERIALS AND METHODS: Six patients with skin cancer of the head and neck were treated using electroporation therapy with intratumorally injected bleomycin. Orbital growth, facial nerve proximity, or proximity to cartilage of the external meatus complicated four of these tumors. The intention was curative. The follow-up period was 24 months and included biopsies after 8 weeks.RESULTS: In four of the six patients, one treatment was enough to eradicate the tumor. In one patient, the tumor persisted even after a second treatment with electroporation therapy. A septal cartilage perforation was the only major complication. The cosmetic results were very satisfactory. One additional recurrence was recorded 6 months after the follow-up periodCONCLUSION: Electroporation therapy is a promising new cancer treatment that should be further evaluated as an alternative to surgery, especially in complicated skin cancer.
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- Norby, Faye L, et al.
(author)
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Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation : The AFGen Consortium
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Journal article (peer-reviewed)abstract
- BACKGROUND: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts.METHODS: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score.RESULTS: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04).CONCLUSIONS: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
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| 21. |
- Nyström-Asklin, J., et al.
(author)
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The adjuvant effect of CpG oligodeoxynucleotide linked to the non-toxic B subunit of cholera toxin for induction of immunity against H-Pylori in mice
- 2008
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 67:5, s. 431-440
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Journal article (peer-reviewed)abstract
- The present study was carried out to test the immunostimulatory and adjuvant effects of the non-toxic B subunit of cholera toxin (CTB), CpG oligodeoxynucleotide (ODN) and CpG ODN linked to CTB (CTB-CpG) for generation of immunity against H. pylori in mice. Herein, we showed that CTB-CpG induces more potent proinflammatory cytokine and chemokine responses in the cervical and the mesenteric lymph nodes (CLN and MLN, respectively) cells in vitro compared with those of CTB and CpG ODN. The adjuvant effects of these agents were examined following intranasal immunization of C57Bl/6 mice with H. pylori lysate in combination with CpG ODN, CTB or CTB-CpG. All three immunization regimes resulted in high H. pylori-specific IgG antibody responses; however, only the CTB-CpG and, to some extent, the CpG ODN immunized mice mounted a sustainable IgG2c antibody response. Importantly, mice immunized with H. pylori antigen and CTB-CpG or CpG ODN, but not CTB, developed strong H. pylori-specific proliferative and IFN-gamma responses in their MLN CD4+ T cells upon recall antigen stimulation in vitro. These mice also had significantly lower bacterial load compared with the control-infected mice. Furthermore, the CTB-CpG and the CpG ODN immunized mice developed increased specific IgA antibody responses in their gastrointestinal tracts following H. pylori challenge. These results imply that CTB-CpG and CpG ODN, but not CTB, could serve as nasal adjuvants for induction of a H. pylori-specific Th1 type immunity in MLN and also a specific mucosal IgA antibody response in the gastrointestinal tract upon H. pylori challenge.
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