Fredrik U. Jönsson

Aesthetics and preferences of web pages

The first impressions of web pages presented to users was investigated by using 13 different web pages, three types of scales and 18 participants. Multidimensional analysis of similarity and preference judgements found four important dimensions: beauty, mostly illustrations versus mostly text, overview and structure. Category scales indicated the existence of two factors related to formal aspects and to appeal of the objects, respectively. The best predictor for the overall judgement of the category scales was beauty. Property vector fitting of the multidimensional solutions with the category scales further indicated the importance of beauty for the preference space. Aspects of usability, product design and aesthetics are discussed.

Cohort studies of association between self‐reported allergic conditions, immune‐related diagnoses and glioma and meningioma risk

An inverse association between self‐reported allergies and glioma and meningioma risk, has been previously observed in case‐control studies. Approximately 27% (median) of the information on both glioma and meningioma in these studies, however, is collected from proxy respondents. In fact, the odds ratios (OR) among previous brain tumor studies are inversely related to the proportion of proxy respondents (Pearson correlation coefficient = −0.94; 95% CI = −1.00 to −0.65); this correlation suggests bias. We therefore constructed 3 cohorts based on the Swedish Twin, Hospital Discharge, and Cancer Registries. In Cohorts I (14,535 people developed 37 gliomas and 41 meningiomas) and II (29,573 people developed 42 gliomas and 26 meningiomas) median time from self‐report of allergies to brain tumor diagnosis was 15.4 years. Cohort III, which overlaps with Cohorts I and II (52,067 people developed 68 gliomas and 63 meningiomas), was linked to the Swedish Hospital Discharge Registry where pre‐brain tumor immune‐related discharge diagnoses were recorded. Allergies are inversely associated with glioma risk in Cohort I (Hazard ratio [HR] = 0.45; 95% CI = 0.19–1.07) and among high grade (III and IV, HR = 0.45; 95% CI = 0.11–1.92) but not low grade (I and II, HR = 2.60; 95% CI = 0.86–7.81) gliomas in Cohort II. In Cohort III, immune‐related discharge diagnoses are also inversely associated with glioma (HR = 0.46; 95% CI = 0.14–1.49). There is no strong evidence against (and some for) the hypothesis that allergies reduce glioma risk.

Occupational magnetic field exposure and neurodegenerative disease.

Background Several studies have identified occupational exposure to extremely low-frequency electromagnetic fields (EMF) as a potential risk factor for neurodegenerative disease, but the evidence is contradictory and inconclusive Methods We conducted a cohort study to explore these associations. We studied all economically active individuals in the Swedish 1980 census (4,812,646 subjects), and followed them for neurodegenerative disease mortality from 1981 through 1995. Information about occupation was available for 1970 and 1980. A job-exposure matrix based on magnetic field measurements was used to assess EMF exposure Results An increased risk of Alzheimer’s disease mortality was observed among men exposed both in 1970 and 1980 (relative risk = 2.3; 95% confidence interval = 1.6-3.3 for exposure ≥0.5 &mgr;T). The associations were most pronounced for early-onset Alzheimer’s disease mortality or with follow-up limited to 10 years after the last known occupation. Amyotrophic lateral sclerosis was not associated with EMF exposure, but the risk estimate with “electrical and electronics work” was 1.4 (95% confidence interval = 1.1-1.9) Conclusions Our study gives some support to the hypothesis that EMF exposure increases the risk of early-onset Alzheimer’s disease, and suggests that magnetic field exposure may represent a late-acting influence in the disease process. Electric shock is an unlikely explanation for the increased risk of amyotrophic lateral sclerosis in “electrical and electronics work” in this study.

Obesity and hormone‐dependent tumors: Cohort and co‐twin control studies based on the Swedish Twin Registry

Obesity increases the risk of certain cancer types, e.g., cancer of the endometrium, colon and gallbladder. For some other cancer forms, e.g., prostate cancer, the association is less clear. We examined the association between body mass index (BMI) and hormone-dependent tumors, utilizing a cohort of 21,884 Swedish twins born during 1886-1925. Information about BMI at different ages and potential confounding factors was collected prospectively. The Swedish Cancer Registry was used to identify cases of cancer in the prostate (n = 666), breast (n = 607), corpus uteri (n = 150) and ovary (n = 118) during 1969-1997. The material was analyzed as a traditional cohort and with co-twin control analyses that allow for control of genetic influences. Obesity (BMI >/=30 kg/m(2)) at baseline was positively associated with cancer in the corpus uteri [relative risk (RR) = 3.03, 95% confidence interval (CI) 1.82-5.03], as was BMI at age 25, independently of BMI at baseline. Increased risk was also found for breast cancer but only in older women (>/=70 years). Overweight at age 25 was associated with decreased risk of breast cancer (RR = 0.51, 95% CI 0.33-0.78). No association was found for prostate cancer. We conclude that age is an important effect modifier of cancer risk associated with obesity and that obesity and overweight in young adult life may affect cancer risk also later in life.Obesity increases the risk of certain cancer types, e.g., cancer of the endometrium, colon and gallbladder. For some other cancer forms, e.g., prostate cancer, the association is less clear. We examined the association between body mass index (BMI) and hormone-dependent tumors, utilizing a cohort of 21,884 Swedish twins born during 1886–1925. Information about BMI at different ages and potential confounding factors was collected prospectively. The Swedish Cancer Registry was used to identify cases of cancer in the prostate (n = 666), breast (n = 607), corpus uteri (n = 150) and ovary (n = 118) during 1969–1997. The material was analyzed as a traditional cohort and with co-twin control analyses that allow for control of genetic influences. Obesity (BMI ≥30 kg/m2) at baseline was positively associated with cancer in the corpus uteri [relative risk (RR) = 3.03, 95% confidence interval (CI) 1.82–5.03], as was BMI at age 25, independently of BMI at baseline. Increased risk was also found for breast cancer but only in older women (≥70 years). Overweight at age 25 was associated with decreased risk of breast cancer (RR = 0.51, 95% CI 0.33–0.78). No association was found for prostate cancer. We conclude that age is an important effect modifier of cancer risk associated with obesity and that obesity and overweight in young adult life may affect cancer risk also later in life.

Lifestyle factors and pancreatic cancer risk: A cohort study from the Swedish Twin Registry

Dear Sir, Even though pancreatic cancer is the 5th-leading cause of cancer deaths in the Western world,1 little is known about the etiology of the disease. Lifestyle and other risk factors for pancreatic cancer have been examined in many epidemiologic studies, most of which were case-control studies. The conclusions of many of these are dubious because of small sample size, low participation and use of proxy respondents. Only cigarette smoking stands out as a likely causal agent in epidemiologic studies. However, cigarette smoking can explain only about 25% of the incidence.2 Studies have also suggested that coffee, ethanol, obesity, high energy intake and high consumption of fat, carbohydrates and animal protein may be risk factors.3–5 Some studies have shown decreased risks associated with frequent consumption of fruits and vegetables, but this has not been observed consistently.3 It is possible that factors other than those that have been investigated may affect the development of pancreatic cancer. Our study examined the effects of diet, coffee, ethanol, tobacco use, BMI, physical activity and change in body weight on pancreatic cancer incidence in a cohort study of twins established in 1958 and followed by the Swedish Twin Registry. The cohort, which provided prospective information concerning exposure, included male and female same-sexed twin pairs who were born from 1886–1925 and were both living in Sweden in 1961. At the 1961 baseline, self-administered questionnaires regarding lifestyle factors were mailed to 25,778 registrees. However, 1,288 of these were found to have already died. Additional questionnaires were administered in 1963 and 1967. Our current study included 12,204 females and 9,680 males who responded to these questionnaires with information on at least some of the potential risk factors. The overall response rate to the questionnaires was 85%. Subjects with pancreatic cancer were included in the analysis only if the diagnosis was made from 1969–97. Ninety percent of the tumors were histologically confirmed. The median age at enrollment in the cohort was 56 years. Subjects were followed from exposure assessment to 1 of 3 study endpoints: diagnosis of pancreatic cancer, death or the end of the study on December 31, 1997. Cancer incidence was ascertained by record linkage to the Swedish Cancer Registry (documented to be 98% complete).6 Death was ascertained by linkage to the Swedish Cause of Death Registry. During the follow-up period (median 16 years), there were 176 incident cases of pancreatic cancer diagnosed at a median age of 73 years. The total number of pancreatic cancer cases included in the risk analysis of each lifestyle factor is less than 176 incident cases because some subjects did not answer all the questions on the questionnaires. The internal dropout rate varied considerably between the different questions. In the questionnaires, smoking status was assessed as nonsmoker, former smoker or current smoker. Current smokers reported the number of cigarettes smoked per day and were coded as light (1–10 cigarettes/day) and regular (11 /day) based on the combination of responses to the questionnaires in 1961 and 1967. Ethanol consumption was self-reported in 1967 as amount and frequency of beer, wine and spirits intake. Ethanol consumption was coded as grams pure ethanol per month (Table I). Coffee consumption was assessed as number of cups per day (Table I). The 1967 questionnaires also included questions about the frequency of consumption of 10 food groups: fruit/vegetables, eggs, pork, beef, sausages, fish, potatoes, flour/grain products, pastry and sweets. The response alternatives were no part, a small part, a moderate part and a large part of the diet (for pastry and sweets: less than daily, daily and several times a day) . The alternatives no part and a small part were combined as low or no part for analysis. Physical activity during leisure hours was assessed as low (responses were hardly any physical exercise or light physical exercise, e.g., regular walks, light gardening) and high (responses were regular exercise or hard physical training). Physical activity at work was assessed as sedentary or physical (responses were physical or hard physical). Weight was selfreported in kilograms and height in centimeters. BMI (in kg/ m) was used as a measure of relative body weight. BMI scores were divided into 4 groups according to WHO criteria for thinness and overweight.7 BMI 18.5–24.99 was selected as the reference category. Weight was self-reported for the actual age when the subject answered the questionnaire and for ages 25 and 40. Adult weight gain was assessed by subtracting weight at age 25 years from weight at enrollment. The relative risk of pancreatic cancer was estimated through Cox proportional hazards modeling using the SAS program

Prior Hospitalization for Epilepsy, Diabetes, and Stroke and Subsequent Glioma and Meningioma Risk

We conducted a case-control study to evaluate the preclinical association between epilepsy, diabetes, and stroke and primary adult brain tumors. We first identified all 1,501 low-grade glioma, 4,587 high-grade glioma (HGG), and 4,193 meningioma cases reported to the Swedish Cancer Registry from 1987 to 1999. Next, controls (137,485) were randomly selected from the continuously updated Swedish Population Registry and matched to cases diagnosed that year on age and sex. Finally, cases and controls were linked to the Swedish Hospital Discharge Registry (1969-1999). We found that ≥8 years before HGG diagnosis (or control reference year) there was an elevated risk of HGG among people discharged with epilepsy [odds ratio (OR), 3.01; 95% confidence interval (95% CI), 1.73-5.22]. Two to 3 years before HGG diagnosis, this risk increased (OR, 5.33; 95% CI, 3.58-7.93) and was especially strong among people ages <55 years (OR, 13.49; 95% CI, 6.99-25.94). During this 2- to 3-year prediagnostic period, we also found an increased risk of HGG among people discharged with meningitis (OR, 3.02; 95% CI, 1.06-8.59) or viral encephalitis (OR, 12.64; 95% CI, 2.24-71.24). Results are similar for glioblastoma multiforme, low-grade glioma, and meningioma. In contrast, risk of HGG among people discharged with diabetes or stroke does not increase until year of brain tumor diagnosis. The occurrence of excess epilepsy ≥8 years before HGG diagnosis suggests a relatively long preclinical phase, but excess diabetes or stroke appear late in HGG development.

Bayesian estimation of variability in adipose tissue blood flow in man by physiologically based pharmacokinetic modeling of inhalation exposure to toluene

Due to the lipophilicity of many xenobiotics, the perfusion of fat tissue is of special interest in physiologically based pharmacokinetic (PBPK) modeling. In order to estimate inter- and intra-individual variability in fat tissue blood flow with exercise, a population PBPK model for toluene was fitted to experimental data from subjects exposed to toluene vapors (Carlsson, A., 1982. Exposure to toluene: uptake, distribution and elimination in man. Scand. J. Work Environ. Health 8, 43-55). Six male volunteers were exposed to 80 ppm toluene for two hours during rest and moderate to heavy exercise (50-150 W). Extensive data collection was made, including sampling of arterial blood, exhaled breath and subcutaneous fat tissue. The model was simultaneously fitted to the time courses of toluene in arterial blood, exhaled breath, and subcutaneous fat in the six individuals by Markov chain Monte Carlo (MCMC) simulation. In order to describe the experimental observations in subcutaneous fat accurately, the fat compartment was split in two. According to the analysis, the increased perfusion of perirenal fat associated with physical workload was best described if it was set to the same, elevated, level during all exercise levels, rather than scaled directly to the increase in oxygen uptake. No increase in subcutaneous fat perfusion could be detected at these exposure conditions.

Affected by Smells? Environmental Chemical Responsivity Predicts Odor Perception

Strong negative reactions, physical symptoms, and behavioral disruptions due to environmental odors are common in the adult population. We investigated relationships among such environmental chemosensory responsivity (CR), personality traits, affective states, and odor perception. Study 1 showed that CR and neuroticism were positively correlated in a sample of young adults (n = 101), suggesting that persons high in neuroticism respond more negatively to environmental odors. Study 2 explored the relationships among CR, noise responsivity (NR), neuroticism, and odor perception (i.e., pleasantness and intensity) in a subset of participants (n = 40). High CR was associated with high NR. Regression analyses indicated that high CR predicted higher odor intensity ratings and low olfactory threshold (high sensitivity) predicted lower pleasantness ratings. However, neuroticism was not directly associated with odor ratings or thresholds. Overall, the results suggest that CR and odor thresholds predict perceptual ratings of odors and that high CR is associated with nonchemosensory affective traits.

The Bayesian population approach to physiological toxicokinetic /toxicodynamic models*/an example using the MCSim software

The calibration of physiologically based toxicokinetic models against experimental data encompasses the merging of prior knowledge with information present in the data. This prior knowledge is manifested in the scientific literature and associated with various degrees of uncertainty. The most convenient way to combine these sources of information is via the use of Bayesian statistical methods. Furthermore, toxicokinetic models are subject to both inter- and intra-individual variability. This variability may be handled statistically by the use of a population model. The MCSim software, which is available for free download on the Internet, permits the use of a population model in combination with a Bayesian statistical approach. An example of the use of MCSim in a recent model-based risk assessment of dichloromethane (DCM) is given and discussed.

Occupational exposure to UV light and mortality from multiple sclerosis.

BACKGROUND The etiology of multiple sclerosis (MS) is largely unknown; low exposure to ultraviolet (UV) light has been a suggested risk factor. The aim of this study was to investigate whether occupational exposure to UV light reduces the risk of death from MS. METHODS The cohort was based on all individuals in the Swedish census in 1980. All MS-related deaths were identified in the national registry of causes of death. A job-exposure matrix was developed to classify the occupational exposure to UV light. RESULTS MS was recorded as a cause of the death for 839 individuals. The risk of MS-related death decreased with increasing occupational exposure to UV light. The relative risk adjusted for age, sex, and socioeconomic status was 0.48 (95% CI 0.28-0.80) in the high-exposure group and 0.88 (95% CI 0.73-1.06) in the intermediate-exposure group. CONCLUSIONS Occupational exposure to UV light was associated with a reduced risk of MS. Our findings are corroborated by previous observations that UV light has a preventive role in the development of MS, although the possibility of reversed causality cannot be completely ruled out.