Showcasing MESMER-X: Spatially Resolved Emulation of Annual Maximum Temperatures of Earth System Models.

Emulators of Earth System Models (ESMs) are complementary to ESMs by providing climate information at lower computational costs. Thus far, the emulation of spatially resolved climate extremes has only received limited attention, even though extreme events are one of the most impactful aspects of climate change. Here, we propose a method for the emulation of local annual maximum temperatures, with a focus on reproducing essential statistical properties such as correlations in space and time. We test different emulator configurations and find that driving the emulations with global mean surface temperature offers an optimal compromise between model complexity and performance. We show that the emulations can mimic the temporal evolution and spatial patterns of the underlying climate model simulations and are able to reproduce their natural variability. The general design and the good performance for annual maximum temperatures suggest that the proposed methodology can be applied to other climate extremes.

Lifestyle and 25-hydroxy-vitamin D among community-dwelling old adults with dementia, mild cognitive impairment, or normal cognitive function.

BACKGROUND: Several studies have indicated that older adults with cognitive impairment have a poorer lifestyle than their healthy peers including lower 25-hydroxy-vitamin D levels (25OHD). AIM: To investigate the associations between lifestyle and 25OHD depending on cognitive status among old adults. METHODS: Community-dwelling old adults (65-96 years) participated in this cross-sectional study based on the Age-Gene/Environment-Susceptibility-Reykjavik-Study. The analytical sample included 5162 subjects who were stratified by cognitive status, i.e., dementia (n = 307), mild cognitive impairment (MCI, n = 492), and normal cognitive status (NCS, n = 4363). Lifestyle variables were assessed and 25OHD was measured. The associations between lifestyle and 25OHD were calculated using linear models correcting for potential confounders. RESULTS: According to linear regression models, 25OHD was significantly lower in older people with dementia (53.8 ± 19.6 nmol/L) than in NCS participants (57.6 ± 17.7 nmol/L). Cod liver oil (7.1-9.2 nmol/L, P < 0.001) and dietary supplements (4.4-11.5 nmol/L, P < 0.001) were associated with higher 25OHD in all three groups. However, physical activity ≥ 3 h/week (2.82 nmol/L, P < 0.001), BMI < 30 kg/m2 (5.2 nmol/L, P < 0.001), non-smoking (4.8 nmol/L, P < 0.001), alcohol consumption (2.7 nmol/L, P < 0.001), and fatty fish consumption ≥ 3x/week (2.6 nmol/L, P < 0.001) were related to higher 25OHD in NCS only, but not in participants with dementia or MCI. DISCUSSION: Older people living in Iceland with dementia are at higher risk for 25OHD deficiency when compared to healthy individuals. Physical activity reported among participants with dementia, and MCI is low and is not significantly associated with 25OHD. CONCLUSIONS: Lifestyle factors among NCS participants are associated with 25OHD levels. Importantly, healthy lifestyle should be promoted among individuals with MCI and dementia.

Drought Persistence Errors in Global Climate Models.

The persistence of drought events largely determines the severity of socioeconomic and ecological impacts, but the capability of current global climate models (GCMs) to simulate such events is subject to large uncertainties. In this study, the representation of drought persistence in GCMs is assessed by comparing state-of-the-art GCM model simulations to observation-based data sets. For doing so, we consider dry-to-dry transition probabilities at monthly and annual scales as estimates for drought persistence, where a dry status is defined as negative precipitation anomaly. Though there is a substantial spread in the drought persistence bias, most of the simulations show systematic underestimation of drought persistence at global scale. Subsequently, we analyzed to which degree (i) inaccurate observations, (ii) differences among models, (iii) internal climate variability, and (iv) uncertainty of the employed statistical methods contribute to the spread in drought persistence errors using an analysis of variance approach. The results show that at monthly scale, model uncertainty and observational uncertainty dominate, while the contribution from internal variability is small in most cases. At annual scale, the spread of the drought persistence error is dominated by the statistical estimation error of drought persistence, indicating that the partitioning of the error is impaired by the limited number of considered time steps. These findings reveal systematic errors in the representation of drought persistence in current GCMs and suggest directions for further model improvement.

Rare and Common Variants Conferring Risk of Tooth Agenesis.

We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach.

Predictors of recurrence of multidrug-resistant and extensively drug-resistant tuberculosis.

OBJECTIVE: To assess the treatment outcome of the first Green Light Committee (GLC) approved countrywide management of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) in Estonia and to evaluate risk factors contributing to TB recurrence over 8 years of follow-up. DESIGN: Prospective assessment of MDR- and XDR-TB patients starting second-line anti-tuberculosis drug treatment between 1 August 2001 and 31 July 2003, with follow-up until 31 December 2010. RESULTS: In 211 MDR- and XDR-TB patients, treatment success was 61.1%; 22.3% defaulted, 8.5% failed and 8.1% died. TB recurrence among successfully treated patients was 8.5%, with no significant difference between XDR-TB and MDR-TB. TB recurrence was associated with resistance to all injectables (HR 2.27, 95%CI 1.16-5.06, P = 0.046), resistance to a greater number of drugs (HR 1.35, 95%CI 1.11-1.64, P = 0.003), and sputum smear positivity (HR 2.16, 95%CI 1.16-4.00, P = 0.016). A history of previous TB treatment was associated with TB recurrence among successfully treated patients (HR 4.28, 95%CI 1.13-16.15, P = 0.032). CONCLUSIONS: The internationally recommended Category IV treatment regimens are sufficiently effective to cure 75% of adherent MDR- and XDR-TB patients. A history of previous treatment, resistance to all injectable agents and resistance to a greater number of drugs increase the recurrence of MDR- and XDR-TB.

C-reactive protein in migraine sufferers similar to that of non-migraineurs: the Reykjavik Study.

C-reactive protein (CRP), a marker of inflammation, has been associated with cardiovascular disease. Risk of cardiovascular disease is increased in migraineurs with aura. Results from a clinical report, case-control and a cohort study suggest that CRP is elevated in migraineurs compared with non-migraineurs. We examined the proposed association in a case-control study nested within two large population-based studies. The relationship between migraine and CRP (high-sensitivity CRP) was studied in 5906 men and women aged 55.0 +/- 8.5 years in the Reykjavik Study and 1345 men and women aged 27.7 +/- 5.5 years from the Reykjavik Study for the Young. A modified version of the International Headache Society's criteria was used to categorize people into migraineurs (two or more symptoms) or non-migraineurs. Migraineurs with visual or sensory symptoms were further defined as having migraine with aura (MA) or without aura (MO). Multivariable-adjusted CRP levels were similar in migraineurs and non-migraineurs for men (0.83 vs. 0.79 mg/l, P = 0.44) and for women (0.87 vs. 0.87 mg/l, P = 0.90). When further stratified by migraine aura and age, no differences were found between non-migraineurs, MO and MA among men. In women, CRP levels were borderline higher in those with MO compared with non-migraineurs and those with MA (1.01 mg/l vs. 0.81 and 0.75 mg/l, P = 0.08 and P = 0.08) in age group 19-34 years, but significantly lower in age group 60-81 years (0.52 mg/l vs. 1.07 and 1.01 mg/l, P = 0.007 and P = 0.03). CRP levels were not increased among migraine sufferers compared with non-migraineurs. Older women migraineurs without aura had lower CRP values than non-migraineurs and migraineurs with aura.

Migraine patients have lower systolic but higher diastolic blood pressure compared with controls in a population-based study of 21,537 subjects. The Reykjavik Study.

Several studies have explored a possible association between migraine and hypertension, with contradictory results. Because of this uncertainty the relation between blood pressure (BP) and migraine was studied in 10,366 men and 11,171 women in a population-based longitudinal study. A modified version of the 1988 International Headache Society criteria was used for diagnosis of migraine. Logistic regression analysis was used. The crude 1-year prevalence of migraine was 5.2% among men and 14.1% among women. No significant association was found between hypertension and migraine. For a one standard deviation (SD) increase in diastolic BP the probability of having migraine increased 14% (P = 0.11) for men and 30% (P < 0.0001) for women. For a 1-SD increase in systolic BP the probability of having migraine decreased 19% (P = 0.007) for men and 25% (P < 0.0001) for women. It was also found that for a 1-SD increase in pulse pressure the probability of having migraine decreased 13% (P = 0.005) for men and 14% (P < 0.0001) for women. In a population-based study of men and women it was found that subjects with migraine had lower pulse pressure, lower systolic BP and higher diastolic BP compared with controls.

Risk profiles and prognosis of treated and untreated hypertensive men and women in a population-based longitudinal study: the Reykjavik Study.

The aim was to examine the risk profiles and prognosis of treated and untreated hypertensive subjects and examine to what degree confounding by indication was present in a population-based cohort study with up to 30-year follow-up. The study population consisted of 9328 men and 10 062 women, aged 33-87 years at the time of attendance from 1967 to 1996. The main outcome measures were myocardial infarction (MI), cardiovascular disease (CVD) mortality and all-cause mortality. Comparing the risk profiles between treated and untreated subjects entering the study showed significantly higher values for some risk factors for treated subjects. During the first 10 years, hypertensive men without treatment, compared with those treated, had a significantly lower risk of suffering MI, CVD and all-cause mortality, hazard ratio (HR) 0.72 (95% CI; 0.57, 0.90), 0.75 (95% CI; 0.59, 0.95) and 0.81 (95% CI; 0.61, 0.98), respectively. No significant differences in outcome were seen during the following 20 years. In identically defined groups of women, no significant differences in mortality were seen between groups. Subgroup analysis, at two stages of the study 5 years apart, revealed that some cardiovascular risk factors had a higher prevalence in hypertensive men who were treated at the later stage, compared with those who remained untreated (P=0.004). In conclusion, hypertensive treated men had a worse prognosis during the first 10 years of follow-up than untreated ones, which is most likely due to worse baseline risk profile. Hypertensive men that were treated at a later stage had a worse risk profile than those not treated at a later stage.

Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up.

OBJECTIVE: To evaluate the efficacy of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year. DESIGN: Placebo controlled, double blind trial. SETTING: Reykjavik health centre. SUBJECTS: 237 smokers aged 22-66 years living in or around Reykjavik. INTERVENTIONS: Nicotine patch for 5 months with nicotine nasal spray for 1 year (n=118) or nicotine patch with placebo spray (n=119). Treatment with patches included 15 mg of nicotine for 3 months, 10 mg for the fourth month, and 5 mg for the fifth month, whereas nicotine in the nasal spray was available for up to 1 year. Both groups received supportive treatment. MAIN OUTCOME MEASURE: Sustained abstinence from smoking. RESULTS: Sustained abstinence rates for the patch and nasal spray group and patch only group were 51% v 35% after 6 weeks (odds ratio 1.97, 95% confidence interval 1.17% to 3.32; P=0.011(chi2), 37% v 25% after 3 months (1.76, 1.01 to 3.08; P=0.045), 31% v 16% after 6 months (2.40, 1.27 to 4.50; P=0.005), 27% v 11% after 12 months (3.03, 1.50 to 6.14; P=0.001), and 16% v 9% after 6 years (2.09, 0.93 to 4.72; P=0.08) [corrected]. CONCLUSIONS: Short and long term abstinence rates show that the combination of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year is a more effective method of stopping smoking than using a patch only. The low percentage of participants using the nasal spray at 1 year, and the few relapses during the second year, suggest that it is not cost effective to use a nasal spray for longer than 7 months after stopping a patch.

The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial.

AIMS: Nicotine replacement therapy (NRT) is an established aid in stopping smoking, while the role of antidepressants remains uncertain. Antidepressants added to NRT might improve abstinence rates. Our aim was to determine the efficacy of nicotine inhaler and fluoxetine vs. nicotine inhaler and placebo in attempts to quit smoking. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: A smoker's cessation clinic. PARTICIPANTS: One hundred volunteers smoking 10 cigarettes/day or more. INTERVENTIONS: Subjects were instructed to start taking a daily dose of 10 mg of fluoxetine or placebo 16 days before stopping smoking, then 20 mg 10 days before quitting, continuing for up to at least 3 months. Subjects were instructed to use 6-12 units per day of nicotine inhalers after stopping smoking for up to 6 months. MEASUREMENTS: Continuous abstinence rates recorded at various time points up to 12 months from the quit date. FINDINGS: The sustained abstinence rate for the inhaler-fluoxetine group was 54%, 40%, 29% and 21% after 1.5, 3, 6 and 12 months, respectively, compared to 48%, 40%, 32% and 23% for the inhaler-placebo group. The differences were not significant at any time point. Abstinence up to 3 months was more likely in older smokers, those with a lower Beck Depression Inventory Score (BDI), lower Fagerström Test of Nicotine Dependence (FTND) score and no history of alcoholism. Fluoxetine appeared to increase abstinence rates among high BDI smokers compared to high BDI smokers assigned placebo. Serum levels of nicotine during treatment in the inhaler-fluoxetine group were lower than in the inhaler-placebo group so that fluoxetine may have reduced inhaler use through a common site of action. CONCLUSIONS: We found no evidence that fluoxetine treatment when used as an adjunct to NRT in unselected smokers is effective, but there may be an advantage to using it in depressed smokers.

What is the long term value of multiphasic health screening and the initial judgement of benefit?

The long term effects of multiphasic health screening (MHS) are rarely studied. In 1964 a random sample of 546 women and 544 men born 1899, 1904, 1909, 1914 or 1919 equally distributed on cohorts from the Swedish town Eskilstuna were invited to examination. For several reasons 167 persons (15%) did not participate in the study. In 1969 the whole sample was invited to a second MHS together with a control group that had not been exposed to MHS. Furthermore, 79 of those alive 1989 born 1899 or 1904 and examined 1964 and 1969 were reexamined. Over all survival rate 1989 for those examined 1964 was for males 18% and for females 35%. Screening instruments 1964 and 1969 were questionnaires, laboratory tests, antropometric measurements, ECG, measurement of blood pressure, chest radiography, peak expiratory flow (PEF), tonometry and fundoscopy of the eyes, audiometric screening, dental, gynecological and general clinical examination. Systolic hypertension for both sexes, low PEF and smoking, low cholesterol in women were negatively related to survival. Of 18 diabetics only one was alive at follow-up. No association was found between BMI and mortality for men, but some (1964 p < 0.01; 1969 p < 0.05) for women. Altogether 87 individuals were 1969 judged to have had some benefit of the MHS in 1964, 40 of them substantial. This was, however, not statistically significantly associated with improved survival. Of the reexamined survivors 86% reported to be generally satisfied with their life situation. The prognostic value of graded benefit was analysed in some detail. The survival to age 85 in the group allotted any benefit was somewhat less good (37%) than in the group with no benefit (44%). The difference did not reach statistical significance.