Quantum Field Theory with Classical Sources - Linearized Quantum Gravity

In a previous work and in terms of an exact quantum-mechanical framework, $\hbar$-independent causal and retarded expectation values of the second-quantized electro-magnetic fields in the Coulomb gauge were derived in the presence of a conserved classical electric current. The classical $\hbar$-independent Maxwell's equations then naturally emerged. In the present work, we extend these considerations to linear gravitational quantum deviations around a flat Minkowski space-time in a Coulomb-like gauge. The emergence of the classical causal and properly retarded linearized classical theory of general relativity with a conserved classical energy-momentum tensor is then outlined. The quantum-mechanical framework also provides for a simple approach to classical quadrupole gravitational radiation of Einstein and microscopic spontaneous graviton emission and/or absorption processes

New regression models for long-term cognitive change in Donepezil treated Alzheimer patients.

Objectives: To analyse and present regression models that can describe the long-term change in cognitive function (MMSE and ADAS-cog) of patients treated with donepezil for three years (n=435). Methods: The Swedish Alzheimer Treatment Study (SATS) is an open, 3-year, multicentre study in a routine clinical setting. Patients with the diagnosis of Alzheimer’s Diseases received the cholinesterase inhibitor donepezil. The patients were assessed with several rating scales including MMSE, ADAS-cog at baseline and every 6 months for a total period of three years. In the first model we used a 6-month interval method. A regression model was fitted from the variables change in score between visits and the baseline score. For the 269 patients with at least 4 assessments each we also calculated a longitudinal regression model for the dependent variable ADAS-cog score at different intervals. In addition, we compared the scores from our model with those predicted by the Stern equation. Results: There was a significant quadratic component between baseline scores on MMSE and ADAS-cog and 6 months mean cognitive change (p<0,05). The 6 months rate of cognitive change in donepezil treated patients was strongly dependent on the baseline scores. The longitudinal regression model for the 269 patients showed that multiple linear regression analysis could be used to predict ADAS-cog score at different intervals (p<0,001). A different slope was observed between our model and the Stern equation. Conclusions: Regression models can predict the outcome of cognitive changes in donepezil treated patients. We also observed different outcomes compared to previous models concerning untreated patients

Successful radioimmunotherapy of established syngeneic rat colon carcinoma with 211At-mAb.

Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with α-emitting radionuclides such as astatine-211 (211At). Radioimmunotherapy utilizing α-particle emitting radionuclides is considered especially suitable for the treatment of small cell clusters and single cells, although lesions of different sizes may also be present in the patient. The aim of this study was primarily to evaluate the toxicity and secondarily in vivo efficacy of a 211At-labeled monoclonal antibody (mAb) directed against colon carcinoma with tumor diameters of approximately 10 mm

Early postnatal nutrition after preterm birth and cardiometabolic risk factors in young adulthood

Objectives Adults born preterm at very low birthweight (VLBW; Study design The Helsinki Study of VLBW Adults includes 166 VLBW and preterm infants born between 1978 and 1985. We collected postnatal nutrition data among 125 unimpaired subjects, who attended two study visits at the mean ages of 22.5 and 25.1 years. We evaluated the effects of energy and macronutrient intakes during the first three 3-week periods of life on key cardiometabolic risk factors with multiple linear regression models. We also report results adjusted for prenatal, postnatal and adult characteristics. Results Macronutrient and energy intakes were not associated with blood pressure, heart rate, or lipid levels in adulthood. Intakes were neither associated with fasting glucose or most other markers of glucose metabolism. An exception was that the first-three-weeks-of-life intakes predicted higher fasting insulin levels: 1 g/kg/day higher protein intake by 37.6% (95% CI: 8.0%, 75.2%), and 10 kcal/kg/day higher energy intake by 8.6% (2.6%, 14.9%), when adjusted for sex and age. These early intakes similarly predicted the adult homeostasis model assessment index. Further adjustments strengthened these findings. Conclusions Among VLBW infants with relatively low early energy intake, early macronutrient and energy intakes were unrelated to blood pressure, lipid levels and intravenous glucose tolerance test results. Contrary to our hypothesis, a higher macronutrient intake during the first three weeks of life predicted higher fasting insulin concentration in young adulthood.Peer reviewe

Polygenic Risk Score of SERPINA6/SERPINA1 Associates with Diurnal and Stress-Induced HPA Axis Activity in Children

Purpose: Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood. Variation in genes SERPINA6 encoding for CBG, SERPINA2 and SERPINAI (serpin family A member 6, 2, and 1) have been shown to influence morning plasma cortisol and CBG in adults. However, association of this genetic variation with diurnal and stress-induced salivary cortisol remain unknown. This study aims to investigate the effect of genetic variation in SERPINA6/2/1 loci on diurnal and stress-induced salivary cortisol in children. Methods: We studied 186, 8-year-old children with genome-wide genotyping. We generated weighted polygenic risk score (PRS) based on 6 genome-wide significant SNPs (rs11621961, rs11629171, rs7161521, rs2749527, rs3762132, rs4900229) derived from the CORNET meta-analyses. Salivary cortisol was measured across one day and in response to the Trier Social Stress Test for Children (TSST-C). Results: Mixed models, adjusted for covariates, showed that the PRS x sampling time interactions associated with diurnal (P <0.001) and stress-induced (P = 0.009) salivary cortisol. In the high PRS group (dichotomized at median) the diurnal salivary cortisol pattern decreased less from awakening to bedtime than in the low PRS group (standardized estimates of sampling time -0.64 vs. -0.73, P <0.0001 for both estimates). In response to stress, salivary cortisol increased in the high PRS group while it remained unchanged in the low PRS group (standardized estimates of sampling time 0.12, P = 0.015 vs. -0.06, P = 0.16). These results were mainly driven by minor alleles of rs7161521 (SERPINA6) and rs4900229 (SERPINAI). Conclusions: Genetic variation in SERPINA6/2/1loci may underpin higher hypothalamic-pituitary-adrenocortical axis activity in children.Peer reviewe

Neurocognitive outcome in young adults born late-preterm

Aim This study examined whether late-preterm birth (34+0 to 36+6wks+d gestational age) was associated with neurocognitive deficit in young adulthood, and whether small for gestational age (SGA) birth amplified any adversity. Method Participants derived from the prospective regional cohort study, the Arvo Ylppö Longitudinal Study (n=786; 398 females, 388 males) (mean age 25y 4mo, SD 8mo), born 1985 to 1986 late-preterm (n=119; 21 SGA, <−2 SD) and at term (37+0 to 41+6wks+d; n=667; 28 SGA) underwent tests of intelligence, executive functioning, attention, and memory, and reported their education. Results Those born late-preterm scored −3.71 (95% confidence interval [CI] −6.71 to −0.72) and −3.11 (95% CI −6.01 to −0.22) points lower on Full-scale and Verbal IQ than peers born at term. Compared with those born at term and appropriate for gestational age (≥−2 to <2 SD) Full-scale, Verbal, and Performance IQ scores of those born late-preterm and SGA were −9.45 to −11.84 points lower. After adjustments, differences were rendered non-significant, except that scores in Full-scale and Performance IQ remained lower among those born late-preterm and SGA. Interpretation Late-preterm birth, per se, may not increase the risk of poorer neurocognitive functioning in adulthood. But the double burden of being born late-preterm and SGA seems to increase this risk

Childhood cognitive ability and physical activity in young adulthood

Objective: Childhood cognitive ability is associated with lifestyle in adulthood, including self-reported physical activity (PA). We examined whether childhood cognitive ability is associated with objectively-measured PA and sedentary time (ST) in young adulthood. Methods: Participants of the Arvo Ylppö Longitudinal Study (n=500) underwent tests of general reasoning, visuo-motor integration, verbal competence and language comprehension at the age of 56 months yielding a general intelligence factor score; at the age of 25 years they wore omnidirectional accelerometers for 9 days (Range=4-10 days) measuring overall daily PA (counts per minute, cpm), ST and light and moderate-to-vigorous PA (MVPA) (minutes), and completed a questionnaire on occupational, commuting, leisure-time conditioning and non-conditioning PA. Results: After adjustment for sex, age, BMI-for-age SD score at 56 months and mean of valid minutes of measurement period for PA, per each one SD increase in the childhood general intelligence factor score, overall daily PA decreased by -8.99 CPM/day, ST increased by 14.93 minutes/day, time spent in light PA decreased by -14.39 minutes/day, and the odds per each level increase in physical demandingness of the work and in time spent in non-conditioning leisure-time PA decreased by 38% and 31%, respectively (p-values<0.04). These associations were mediated via higher young adulthood level of education. Conclusions: In contrast to expected, in this cohort of young adults with high variability in PA, of whom many were still studying, higher childhood cognitive ability was associated with more objectively-measured and self-reported physical inactivity. Whether these findings persist beyond young adulthood is a subject of further studies

Maternal early pregnancy body mass index and diurnal salivary cortisol in young adult offspring

Background Maternal early pregnancy overweight (body mass index [BMI] 25.0-29.9 kg/m(2)) and obesity (BMI >= 30 kg/m(2)) are associated with mental and physical health adversities in the offspring. Prenatal programming of the hypothalamic-pituitary-adrenal (HPA) axis has been put forward as one of the mechanisms that may play pathophysiological role. However, evidence linking maternal overweight and obesity with offspring HPA-axis activity is scarce. We studied if maternal early pregnancy BMI is associated with diurnal salivary cortisol, a marker of HPA-axis activity, in young adult offspring. Methods At a mean age of 25.3 (standard deviation [SD) = 0.6) years, 653 Arvo Ylppo Longitudinal Study participants collected saliva samples for cortisol analyses, at awakening, 15 and 30 min thereafter, 10:30AM, 12:00PM, 5:30PM and at bedtime. Maternal BMI was calculated from weight and height verified by a measurement in the first antenatal clinic visit before 12 weeks of gestation derived from healthcare records. Results Per each one kg/m(2) higher maternal early pregnancy BMI offspring diurnal average salivary cortisol was -1.4% (95% CI:-2.6, -0.2, p(FDR) = 0.033) lower, at awakening it was -2.4% (95% CI:-4.0, -0.7, p(FDR) = 0.025) lower and the morning average salivary cortisol was -2.0% (95% CI:-3.4,-0.5, p(FDR) = 0.017) lower. These associations were independent of the offspring's own young adulthood BMI, and other important covariates. Conclusion Our findings show that young adult offspring born to mothers with higher early pregnancy BMI show lower average levels of diurnal cortisol, especially in the morning. Whether these findings reflect prenatal programming of the offspring HPA-axis activity warrants further investigation.Peer reviewe

Early postnatal nutrition after preterm birth and cardiometabolic risk factors in young adulthood

Adults born preterm at very low birthweight (VLBW; <1500 g) have a non-optimal cardiometabolic risk factor profile. Since higher protein intake during the first weeks of life predicted a healthier body composition in adulthood in our previous studies, we hypothesized that it would also predict a favorable cardiometabolic profile.STUDY DESIGN: The Helsinki Study of VLBW Adults includes 166 VLBW and preterm infants born between 1978 and 1985. We collected postnatal nutrition data among 125 unimpaired subjects, who attended two study visits at the mean ages of 22.5 and 25.1 years. We evaluated the effects of energy and macronutrient intakes during the first three 3-week periods of life on key cardiometabolic risk factors with multiple linear regression models. We also report results adjusted for prenatal, postnatal and adult characteristics.RESULTS: Macronutrient and energy intakes were not associated with blood pressure, heart rate, or lipid levels in adulthood. Intakes were neither associated with fasting glucose or most other markers of glucose metabolism. An exception was that the first-three-weeks-of-life intakes predicted higher fasting insulin levels: 1 g/kg/day higher protein intake by 37.6% (95% CI: 8.0%, 75.2%), and 10 kcal/kg/day higher energy intake by 8.6% (2.6%, 14.9%), when adjusted for sex and age. These early intakes similarly predicted the adult homeostasis model assessment index. Further adjustments strengthened these findings.CONCLUSIONS: Among VLBW infants with relatively low early energy intake, early macronutrient and energy intakes were unrelated to blood pressure, lipid levels and intravenous glucose tolerance test results. Contrary to our hypothesis, a higher macronutrient intake during the first three weeks of life predicted higher fasting insulin concentration in young adulthood.</p

Neonatal Nutrition Predicts Energy Balance in Young Adults Born Preterm at Very Low Birth Weight

Epidemiological studies and animal models suggest that early postnatal nutrition and growth can influence adult health. However, few human studies have objective recordings of early nutrient intake. We studied whether nutrient intake and growth during the first 9 weeks after preterm birth with very low birth weight (VLBW,Peer reviewe