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Studies on intrinsic and extrinsic sources of variability in pharmacokinetics and pharmacodynamics

Popular Abstract in Swedish Variabilitet i ett läkemedels farmakokinetiska (hur ett läkemedel omsätts i kroppen) och farmakodynamiska (vilken effekt ett läkemedel har) egenskaper kan resultera i att olika individer som erhållit samma dos av ett läkemedel får olika effekter av läkemedel. Biverkningar eller utebliven effekt kan innebära allvarliga konsekvenser för den enskilda individen. VariabiliteVariability in pharmacokinetic and pharmacodynamic parameters between individuals can be due to intrinsic and extrinsic factors. In this thesis three different areas regarding sources of variability have been investigated. 1. Formulation properties as an extrinsic source of variability. Lipophilic substances often have poor oral bioavailability and high inter- and intraindividual variability. High

Perinatal factors associated with cerebral palsy in children born in Sweden.

OBJECTIVE: To identify perinatal factors associated with cerebral palsy (CP). METHODS: This was a case-control study based on the Swedish Medical Birth Registry and the Swedish Hospital Discharge Registry, including 2,303 infants born in Sweden 1984-1998 with a diagnosis of CP and 1.6 million infants without this diagnosis. Odds ratios (ORs) with 95% confidence intervals (Cis) were calculated. RES

Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year.

OBJECTIVE—To examine the effects of dipeptidyl peptidase-IV (DPP-4) inhibition on meal-related β-cell function and insulin sensitivity over 52 weeks in type 2 diabetes. RESEARCH DESIGN AND METHODS—In a 12-week core study, placebo (n = 51) or vildagliptin (n = 56; 50 mg OD) was added to metformin treatment (1.5–3.0 mg/day). A 40-week extension followed in 71 patients. Meal tests were performed at

Results of endosonographic imaging of the anal sphincter 2-7 days after primary repair of third- or fourth-degree obstetric sphincter tears.

Objectives To describe the endosonographic image of the anal sphincter 2-7 days after delivery in women who had undergone a primary repair of an obstetric sphincter tear. Methods Forty-eight women who had suffered a third- or fourth-degree sphincter tear at delivery and had undergone primary sphincter repair were examined with endoanal sonography 2-7 days after delivery. A score from 0 to 16 was

Traditional versus agricultural lifestyle among Shuar women of the Ecuadorian Amazon: Effects on leptin levels

Leptin is a key biological marker related to energy balance and development of diabetes and cardiovascular diseases. Its levels are increased in populations with a high degree of the metabolic syndrome. Life history of evolution has, however, largely taken place under the ecological context of hunting and gathering. In this study, we explored whether the first steps of transition to sedentary agri

Contribution of known and unknown susceptibility genes to early-onset diabetes in scandinavia: evidence for heterogeneity.

In an attempt to identify novel susceptibility genes predisposing to early-onset diabetes (EOD), we performed a genome-wide scan using 433 markers in 222 individuals (119 with diabetes) from 29 Scandinavian families with ≥2 members with onset of diabetes ≤45 years. The highest nonparametric linkage (NPL) score, 2.7 (P < 0.01), was observed on chromosome 1p (D1S473/D1S438). Six other regions on chr

Mortality risks among heavy-smokers with special reference to women: a long-term follow-up of an urban population

Increased mortality risks associated with smoking are well established among men. There are very few population-based studies comprising a sufficient number of heavily smoking women, measuring the direct effect of smoking on mortality risks. Between 1974 and 1992, 8,499 women and 13,888 men attended a health screening programme including reporting of smoking habits. Individuals were followed for t

Timing and speed of migration in male, female and juvenile Ospreys Pandion haliaetus between Sweden and Africa as revealed by field observations, radar and satellite tracking

Breeding Ospreys were studied in southern Sweden and 13 birds were tracked by satellite telemetry on autumn migration to the African wintering grounds. This was supplemented with studies of migrating birds at Falsterbo and radar trackings From southern Sweden. Females generally left the nest site 2-3 weeks ahead of males and juveniles. Among males, failed bleeders migrated significantly earlier th

Cerebral blood volume (CBV) in humans during normo- and hypocapnia: influence of nitrous oxide (N(2)O)

BACKGROUND: It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of t

Sugar-sweetened beverage consumption and genetic predisposition to obesity in 2 Swedish cohorts

Background: The consumption of sugar-sweetened beverages (SSBs), which has increased substantially during the last decades, has been associated with obesity and weight gain. Objective: Common genetic susceptibility to obesity has been shown to modify the association between SSB intake and obesity risk in 3 prospective cohorts from the United States. We aimed to replicate these findings in 2 large

Acyl migration in enzymatic interesterification of triacylglycerols : Effects of lipases from Thermomyces lanuginosus and Rhizopus oryzae, support material, and water activity

The enzymatic interesterification of a solvent-free, equimolar mixture of trilaurin and 1,3-palmitin-2-olein was studied using three immobilized lipase preparations as catalysts. Analysis of triacylglycerol (TAG) content and fatty acid (FA) distribution monitored the lipase-catalyzed interesterification in sn-1,3 positions and FA exchange in the sn-2 position caused by acyl migration. Lipase from

The role of the amygdala during emotional processing in Huntington's disease : from pre-manifest to late stage disease

BACKGROUND: Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disrupti

Long-term adjustment to living with an ileal pouch-anal anastomosis

PURPOSE: The aim of this study was to describe long-term adjustment to life with an ileal pouch-anal anastomosis after surgery for ulcerative colitis, to investigate the relationship of pouch function to adjustment, and to explore factors affecting quality of life.METHODS: A total of 369 patients treated between 1982 and 1993 were included in the study. Questionnaires designed to assess bowel (pou

Kan allmän plats tas i anspråk utan ersättning?

Fram till 1 januari 2015 hade länsstyrelsen möjlighet att besluta om ”113-förordnande” enligt 6 kap. 5 § PBL. 113-förordnandet innebar att kommunen kunde ta mark i anspråk utan ersättning om det ansågs skäligt med hänsyn till den nytta som exploatören förväntades få av planens genomförande och till omständigheterna i övrigt. Hur mark för allmän plats ska värderas och ersättas regleras i 4 kap. 3a Until 1st of January 2015, the county administrative board could decide on “113-regulation” according to Ch. 6 Art. 5 Planning and Building Act. The regulation meant that the municipality could claim land for public spaces without compensation if it was fair considering the benefit expected to be achieved by the planer's implementation and the circumstances in general. How public space is to b

Alignment and orientation of Nanowires in a thin film under the influence of an electric field

Produktion av en nanotrådssolcell För att ta itu med miljöpåverkan från växthusgaser krävs en övergång till förnyelsebara energikällor. Ett exempel på en sådan källa är nanotrådssolceller. I mitt examensarbete har jag undersökt hur nanotrådar kan arrangeras på sådant sätt som krävs för att kunna omvandla solljuset till elektricitet. Global uppvärmning är ett hot som till stor del orsakas av utslThe demand for cheaper and more efficient solar cells is high. One way to decrease cost of material, while maintaining a high degree of efficiency, is to take advantage of nanomaterials. A thin film containing pn-junction nanowires can convert light with an efficiency comparable to traditional planar cells, while using a fraction of the material, and thus reduce costs. At the company Sol Voltaics

New Evidence for Selective Reporting in Climate Change Science

Populärvetenskaplig sammanfattning: Är klimatforskningen skev? En central fråga är om vi kan lita på att vetenskapliga tidskrifter återger en rättvis bild av aktuella forskningsresultat? Dessutom bör vi fråga oss hur rapporteringen påverkas då betydande händelser sker inom vetenskapsvärlden. I november 2007 och senare 2009 skedde två viktiga företeelser inom klimatforskningen som potentiellt kanAbstract The declaration of a scientific consensus concerning anthropogenic causes for climate change by the IPCC in their fourth assessment report (AR4), published in 2007, initiated a heated debate. During this debate, experts within the IPCC were accused of selective reporting and the AR4 got strong source criticism by politicians, stakeholders and climate skeptics in general. The debate furth

Evaluation of overheating risks and passive cooling measures in low energy Swedish dwellings

Overheating in buildings is becoming a major concern and cause for various health issues. Existing research and previous studies on the issue were examined to acquire relevant information about the definition of overheating, its possible causes, and the heath impacts it could have on human health. The review included data on the current status of thermal comfort and overheating regulations in Swed

Association between age, gender and multimorbidity level and receiving home health care : a population-based Swedish study

BACKGROUND: Home health care is an important part of primary health care. How delivery of home health care is organised is probably important for sustainability of the healthcare system as a whole. More than 50 % of individuals over 65 years old have multimorbidity, which increases with higher age, also influencing the needs of home health care. Our aim was to study the proportion of the populatio

One-year postpartum anthropometric outcomes in mothers and children in the LIFE-Moms lifestyle intervention clinical trials

Background/objectives: Excess gestational weight gain (GWG) is a risk factor for maternal postpartum weight retention and excessive neonatal adiposity, especially in women with overweight or obesity. Whether lifestyle interventions to reduce excess GWG also reduce 12-month maternal postpartum weight retention and infant weight-for-length z score is unknown. Randomized controlled trials from the LI