Про деякі зв'язки та узагальнення пронормальних підгруп

Отримано нові результати щодо зв'язків та узагальнень пронормальних підгруп. Зокрема, розглянуто групи, кожна циклічна підгрупа яких є самоспряжено-переставною. Наведено повний опис таких груп в деяких дуже широких класах груп, які містять в собі всі скінченні групи.Получены новые результаты относительно связей и обобщений пронормальных подгрупп. В частности, рассмотрены группы, каждая циклическая подгруппа которых является самосопряженно-переставляемой. Приведено полное описание таких групп в некоторых очень широких классах групп, которые содержат в себе все конечные группы.New results concerning the connections and generalizations of pronormal subgroups are presented. In particular, we studied groups, in which every cyclic subgroup is self-conjugate-permutable. We obtained the full description of such groups in some very wide classes of groups which contain all finite groups

Mouse Models for the Study of Viral Hepatitis : (intra)cellular innate immunity

Liver-residing leukocytes are essential in determining the outcome of infection with hepatitis viruses. Patient studies of liver innate immune cells during chronic viral hepatitis have been performed but are hampered by, amongst others, a lack of baseline data and unknown time of infection. Therefore, animal models are essential for the study of the innate immune response in viral hepatitis. In the studies presented in this thesis, we aimed to better understand the cellular innate immune responses in the liver during lymphocytic choriomeningitis virus (LCMV) clone 13 induced chronic hepatitis, and to establish the human-liver chimeric mice as model for chronic Hepatitis E virus (HEV) infections in order to study the intracellular innate immune mechanisms upon HEV infection. In chapter 2 and 3, we aimed to unravel how the cellular innate immune system deals with chronic viral infection in the liver using the LCMV infection mouse model. In chapter 2, we described that early after LCMV infection a functional dichotomy is observed for inflammatory monocytes and F4/80high-Kupffer cells with respect to endocytosis, but their activation and cytokine gene expression profiles exhibit a strong resemblance. In addition, inflammatory monocytes exhibit a huge capacity for recruitment to the liver and plasticity dependent on the nature of the inflammatory signal, either viral or sterile. This suggests that inflammatory monocytes play a crucial role in shaping the inflammatory environment in the liver early after infection. In chapter 3, we showed that LCMV induces chronic viral hepatitis with limited intrahepatic cytokine and interferon responses during the chronic infection. Furthermore, we identified KC and IM as distinct cell populations before, during, and after chronic infection, with important differences in activation status, antigen presentation, and gene ex

Statins and prevention of infections: systematic review and meta-analysis of data from large randomised placebo controlled trials

Objective To evaluate whether the potential of statins to lower the risk of infections as published in observational studies is causal

Adults miscoded and misdiagnosed as having pneumonia: results from the British Thoracic Society pneumonia audit

A key objective of the British Thoracic Society national community-acquired pneumonia (CAP) audit was to determine the clinical characteristics and outcomes of hospitalised adults given a primary discharge code of pneumonia but who did not fulfil accepted diagnostic criteria for pneumonia. Adults miscoded as having pneumonia (n=1251) were older compared with adults with CAP (n=6660) (median 80 vs 78 years, p<0.001) and had more comorbid disease, significantly fewer respiratory symptoms (fever, cough, dyspnoea, pleuritic pain), more constitutional symptoms (general deterioration, falls) and significantly lower 30-day inpatient mortality (14.3% vs 17.0%, adjusted OR 0.75, p=0.003)

Cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands in different age groups

OBJECTIVE: We aimed to assess the cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands. METHODS: A Markov model was used to evaluate the health effects and costs of lung cancer screening from the healthcare perspective. The effects and costs of ten screening scenarios with different start and stop ages of screening were examined across a lifetime horizon in a cohort of 100,000 smokers and ex- smokers 50 years and older. RESULTS: The incremental cost-effectiveness ratios (ICERs) of screening smokers and ex-smokers aged 50-60 years, 50-70 years, and 50 years and older are below the cost-effectiveness threshold of € 20,000 per quality adjusted life year (QALY) gained. Screening 50-60-year-old smokers and ex-smokers was the most cost-effective scenario with an ICER of € 14,094 per QALY gained. However, screening smokers and ex-smokers 50 years and older yielded the highest QALYs and resulted in an ICER of € 16,594 per QALY, which is below the threshold of € 20,000 per QALY. All screening scenarios compared to no screening resulted in CERs between the € 14,000 and € 16,000 per QALY gained. The efficiency frontier showed that screening smokers and ex-smokers in the age groups 70 years and older, 60-70 years, 60 years and older are excluded by extended dominance by no screening, screening smokers and ex-smokers aged 50-60 years and 50-70 years. CONCLUSION: This study showed that lung cancer screening is cost-effective in the Netherlands

Real-world treatment patterns and outcomes of patients with extensive disease small cell lung cancer

Objective: Clinical outcome data on patients with extensive disease small cell lung cancer (ED SCLC) treated in routine practice is limited. The aim of this retrospective study is to present data on treatment patterns and survival in an unselected patient population with ED SCLC. Methods: All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were included. We collected data on patient characteristics, systemic treatments, overall survival (OS), dose reductions ('80% of initial dose) and early discontinuation ('4 cycles). Results: From 792 diagnosed patients, 568 (72%) started with first-line treatment. Of these patients, 41% received second-line treatment. Only 68 patients received third-line treatment. For all treated patients, the mean age was 66 years. The majority (72%) had a performance status (ECOG) of 0 or 1 at diagnosis. Median OS of treated patients was 7.4 months. Of all patients with first-line treatment, 26% received '4 cycles and dose reductions were observed in 29%. Conclusion: After first-line systemic treatment in ED SCLC the fraction of patients receiving subsequent lines of treatment is rapidly decreasing. This information is necessary as background for evaluation of the added value of future drugs under study for ED SCLC

Interferon-alpha treatment rapidly clears Hepatitis e virus infection in humanized mice

Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals. Rapid viral clearance by pegIFNα was confirmed in HEV gt1, but not in Hepatitis B Virus infected animals. No ISG induction was observed in untreated HEV gt3 and gt1 infected humanized livers compared to control chimeric mice, irrespective of the human hepatocyte donor, viral isolate or HEV infection duration. Human specific ISG transcript levels in mouse liver increased significantly after pegIFNα treatment and induced high circulating human CXCL10 in mouse serum. In conclusion, HEV gt1 and gt3 infections do not elicit innate intrahepatic immune responses and remain highly sensitive to pegIFNα in immunocompromised humanized mice

Psychostimulants: Influence on Body Mass Index and Height in a Pediatric Population with Attention-Deficit/Hyperactivity Disorder?

Objectives: Attention-deficit/hyperactivity disorder (ADHD) is often treated with psychostimulants. Psychostimulants' adverse effects on body mass index standard deviation score (BMI-sds) and height in children/adolescents with ADHD have been reported. However, literature is inconsistent, and it is unclear whether the observed effects are dosage- and/or BMI-dependent. Therefore, the aim of this retrospective observational study is to evaluate the influence of psychostimulants on BMI-sds and height-sds in a pediatric cohort with ADHD from an outpatient clinic, and to study the correlation between psychostimulant dosage and BMI-sds and height-sds change.Method: Participants ≤18 years of age diagnosed with ADHD who started with psychostimulants (methylphenidate) were studied. Changes in BMI-sds and height-sds over an 18-month treatment period were assessed in subgroups according to baseline BMI-sds, gender, and age. Furthermore, correlations between BMI-sds, height-sds, and psychostimulant dose were studied.Results: In total, 298 participants [median age 9.8 years, height-sds 0.0, BMI-sds 0.5, psychostimulant dosage 0.5 (0.2–1.4) mg/kg/day] were analyzed, with an underweight, overweight, and obesity prevalence of 5%, 21%, and 7%, respectively. After 18 months of treatment a significant decline in BMI-sds (−0.4) and height-sds (−0.2) was observed. These effects were consistent in all subgroups except for no change in BMI-sds in the underweight subgroup and no change in height-sds in the overweight subgroup. Medication dosage was weakly correlated with change in BMI-sds [r = −0.3 (−0.9 to +0.5); p r = −0.2 (−0.4 to −0.1); p = 0.01].Conclusion: After 18 months of psychostimulant treatment, a significant decline in BMI-sds and height-sds was observed. However, the correlation with psychostimulant dosage was weak, and the decline was not observed in all subgroups. Therefore, further studies on the etiology of BMI-change are warranted, particularly with regard to the ADHD symptoms.Pharmacolog