Long-term risk of cervical cancer following conization of cervical intraepithelial neoplasia grade 3-A Danish nationwide cohort study.

Using nationwide Danish registries we examined the long-term risk of cervical cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (including adenocarcinoma in situ (AIS)) on the cone compared to women with a normal cytology test. Initially, we identified women born 1918-1990, who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. From the Pathology Data Bank information on CIN3 on the cone, margins status, histological type of CIN3 and cervical cytology results was extracted. Cox proportional hazard model was used to estimate the relative risk of subsequent cervical cancer. We included 59,464 women with CIN3 on the cone and 1,918,508 women with a normal cytology test. Overall, women diagnosed with CIN3 had a higher risk of subsequent cervical cancer compared to women with normal cytology (HR = 2.06; 95%CI: 1.81-2.35). Analyses according to time since conization showed elevated risks in all time periods, and 25 years or more after conization the relative risk was significantly increased (HR = 2.56; 95%CI: 1.37-4.77). Twenty years or more after conization, also women with negative margins had an increased relative risk (HR = 2.49; 95%CI: 1.12-5.57). In addition, the long-term relative risk of cervical cancer varied with the different histological types of CIN3 and was highest for AIS (HR = 7.50; 95%CI: 1.87-30.01, 10-14 years after conization). In conclusion, women diagnosed with CIN3 on the cone have a long-lasting increased risk of cervical cancer even when the margins on the cone are negative.

Diabetes is associated with lower tuberculosis antigen-specific interferon gamma release in Tanzanian tuberculosis patients and non-tuberculosis controls.

BACKGROUND: Diabetes is increasingly common in TB endemic regions and plays a role as a possible risk factor for increased progression from latent TB infection (LTBI) to active TB disease. Although the pathophysiological mechanisms are not fully understood, the immune system is weakened in diabetes patients and therefore the validity of interferon gamma release assays (IGRA) may be compromised. The aim of the present study was to assess the association between diabetes and Mycobacterium tuberculosis (Mtb) antigen-specific interferon gamma (IFN-γ) release in a TB endemic area among culture-confirmed TB patients and non-TB controls. METHODS: Culture-confirmed pulmonary TB patients (n = 187) and healthy non-TB neighbourhood controls (n = 190) from Mwanza, Tanzania were tested for the presence of circulating T cells recognizing Mtb antigens using an IGRA. The diabetes status of all participants was assessed using a standard oral glucose tolerance test. The impact of diabetes on the performance of the IGRA was estimated using robust linear and logistic regression. RESULTS: Compared to normal glucose tolerance, diabetes was associated with reduced levels of Mtb-specific IFN-γ. Increasing levels of fasting blood glucose (B - 0.3, 95% confidence interval - 0.6 to - 0.03, p = 0.033) was negatively associated with IFN-γ. Although TB patients had higher specific and lower unspecific mitogen IFN-γ responses compared to non-TB controls, the association between diabetes and IFN-γ did not depend on TB status. CONCLUSION: Diabetes is associated with lower levels of Mtb antigen-specific IFN-γ, and the validity of IFN- γ tests for LTBI may be questionable in individuals with diabetes.

Parasitoids of the cabbage seed weevil deliver high and consistent parasitism in variable landscapes: A showcase of conservation biocontrol.

BACKGROUND: Insect pest resistance to insecticides and societal pressure to reduce pesticide load has increased oilseed rape (OSR) farmers' motivation to protect and exploit parasitoids for pest control. However, parasitoid presence and parasitism must be made visible to influence farmers' spraying decisions. Parasitism of cabbage seed weevil (CSW) (Ceutorhynchus obstrictus (Marsham)) reduces damage to OSR immediately, making them a good case for demonstrating conservation biocontrol to farmers. We assessed the occurrence and activity of CSW parasitoids in 84 OSR fields over 2 years and identified the impact of associated local landscape factors. RESULTS: Mean cabbage seed weevil infestation rates were 11% and 10% in 2020 and 2021, and parasitism rates were high in both years (75% and 74%, respectively). Temporal and spatial dynamics of OSR in the landscape surrounding the focal fields were important for both CSW and parasitoid numbers, suggesting a dilution effect for increasing OSR area since the previous year. A multimodel inference analysis showed that OSR-related factors were important predictors for both the infestation rate of CSW and the number of parasitoids. For parasitoids, protected nature areas and hedgerows were important. Parasitism rates were high and largely unaffected by landscape factors. CONCLUSION: CSW and its parasitoids respond similarly to interannual changes in the OSR resource; in addition, parasitoids benefit from uncropped areas in the surrounding landscape. The complexity of the pest and parasitoid response to landscape factors limits the prospect of designing landscapes for improved pest control by the parasitoids. Parasitoids of CSW may be present as local populations in agricultural landscapes with the potential for consistent and substantial parasitism. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Plant disease detection model for edge computing devices.

In this paper, we address the question of achieving high accuracy in deep learning models for agricultural applications through edge computing devices while considering the associated resource constraints. Traditional and state-of-the-art models have demonstrated good accuracy, but their practicality as end-user available solutions remains uncertain due to current resource limitations. One agricultural application for deep learning models is the detection and classification of plant diseases through image-based crop monitoring. We used the publicly available PlantVillage dataset containing images of healthy and diseased leaves for 14 crop species and 6 groups of diseases as example data. The MobileNetV3-small model succeeds in classifying the leaves with a test accuracy of around 99.50%. Post-training optimization using quantization reduced the number of model parameters from approximately 1.5 million to 0.93 million while maintaining the accuracy of 99.50%. The final model is in ONNX format, enabling deployment across various platforms, including mobile devices. These findings offer a cost-effective solution for deploying accurate deep-learning models in agricultural applications.

Skim milk, whey, and casein increase body weight and whey and casein increase the plasma C-peptide concentration in overweight adolescents.

In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12-15 y with a BMI of 25.4 ± 2.3 kg/m(2) (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein/L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered. Outcomes were BMI-for-age Z-scores (BAZs), waist circumference, plasma insulin, homeostatic model assessment, and plasma C-peptide. We found no change in BAZ in the pretest control and water groups, whereas it was greater at 12 wk in the skim milk, whey, and casein groups compared with baseline and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P < 0.02). There were no significant changes in plasma C-peptide in the skim milk or water group. These data suggest that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated.

Validity of information on atopic disease and other illness in young children reported by parents in a prospective birth cohort study.

BACKGROUND: The longitudinal birth cohort study is the preferred design for studies of childhood health, particularly atopic disease. Still, prospective data collection depends on recollection of the medical history since the previous visit representing a potential recall-bias. We aimed to ascertain the quality of information on atopic disease and other health symptoms reported by parental interview in a closely monitored birth cohort study. Possible bias from symptom severity and socioeconomics were sought. METHODS: Copenhagen study on Asthma in Childhood (COPSAC) is a clinical birth cohort study of 411 children born of asthmatic mothers from 1999 to 2001. Child health is monitored at six-monthly visits with particular emphasis on atopic symptoms and infections. Data from the first three study years on 260 children was compared with records from their family practitioner as an external reference. RESULTS: A total of 6134 medical events were reported at the COPSAC interviews. Additional 586 medical events were recorded by family practitioners but not reported at the interview. There were no missed events related to asthma, eczema or allergy. Respiratory, infectious and skin related symptoms showed completeness above 90%, other diseases showed lower completeness around 77%. There was no meaningful influence from concurrent asthma or socioeconomics. CONCLUSIONS: The COPSAC study exhibited full sensitivity to the main study objectives, atopic disease, and high sensitivity to respiratory, infectious and skin related illness. Our findings support the validity of parental interviews in longitudinal cohort studies investigating atopic disease and illness in childhood.

Obesity, inflammation and metabolic syndrome in Danish adolescents.

AIM: To describe biomarkers of inflammation and markers related to the metabolic syndrome (MS) in healthy obese Danish adolescent and compare to a normal-weight group. METHODS: Fifty-one obese and 30 normal-weight adolescents (12-15 years) were included. Anthropometry and blood pressure were measured, and blood was sampled. RESULTS: Obese adolescents had significantly higher blood pressure, insulin, homeostasis model assessment of insulin resistance, C-peptide, total cholesterol, low-density lipoprotein cholesterol (LDL), triglyceride, C-reactive protein (CRP), interleukin-6 and tumour necrosis factor alpha and lower high-density lipoprotein cholesterol values, compared with normal-weight adolescents, whereas there were no differences between the groups for glucose, free fatty acids or faecal calprotectin. Within the obese group insulin, low-density lipoprotein cholesterol, and CRP were positively associated with body mass index (BMI) Z-scores. The MS was present in 14% of obese adolescents. CRP was positively associated with most anthropometric measures within the obese group, and in multiple linear regression analysis both BMI Z-score and the sum of skin folds explained a considerable part (R(2) = 0.421) of the variation in CRP. CONCLUSION: Otherwise healthy Danish obese adolescents had marked low-grade inflammation, elevated biomarkers of the MS and high prevalence of the MS.

Increased risk of eczema but reduced risk of early wheezy disorder from exclusive breast-feeding in high-risk infants.

BACKGROUND: Breast-feeding is recommended for the prevention of eczema, asthma, and allergy, particularly in high-risk families, but recent studies have raised concern that this may not protect children and may even increase the risk. However, disease risk, disease manifestation, lifestyle, and the choice to breast-feed are interrelated, and therefore, analyzing true causal effects presents a number of methodologic challenges. OBJECTIVE: First, to assess the effect from duration of exclusive breast-feeding on the development of eczema and wheezy disorders during the first 2 years of life in a high-risk clinical birth cohort. Second, to assess any influence from the fatty acid composition of mother's milk on the risk from breast-feeding. METHODS: We studied disease development during the first two years of life of the 411 infants from the Copenhagen Study on Asthma in Childhood (COPSAC) birth cohort, born to mothers with a history of asthma. We analyzed the effect from duration of breast-feeding before disease onset on the disease risk, avoiding the effect from disease-related modification of exposure (inverse causation). Polyunsaturated fatty acids were measured in breast milk. RESULTS: Breast-feeding significantly increased the risk of eczema adjusted for demographics, filaggrin variants, parents' eczema, and pets at home (N = 306; relative risk, 2.09; 95% CI 1.15-3.80; P = .016) but reduced the risk of wheezy episodes (relative risk, 0.67; 95% CI 0.48-0.96; P = .021) and of severe wheezy exacerbation (relative risk, 0.16; 95% CI 0.03-1.01; P = .051). There was no association between the fatty acid composition of mother's milk and the risk of eczema or wheeze. CONCLUSION: The risk of eczema was increased in infants with increasing duration of breast-feeding. In contrast, the risk of wheezy disorder and severe wheezy exacerbations was reduced. There were no significant effects from the fatty acid composition of the breast milk on risk of eczema or wheezy disorders.

Multimodel inference applied to oxygen recovery kinetics after 6-min walk tests in patients with chronic obstructive pulmonary disease.

6-min walk tests (6MWT) are routinely performed in patients with chronic obstructive pulmonary disease (COPD). Oxygen uptake ([Formula: see text]) kinetics during 6MWT can be modeled and derived parameters provide indicators of patients' exercise capacity. Post-exercise [Formula: see text] recovery also provides important parameters of patients' fitness which has not been extensively investigated in COPD. Several nonlinear regression models with different underlying biological assumptions may be suitable for describing recovery kinetics. Multimodel inference (model averaging) can then be used to capture the uncertainty in considering several models. Our aim was to apply multimodel inference in order to better understand the physiological underpinnings of [Formula: see text] recovery after 6MWT in patients with COPD. 61 patients with COPD (stages 2 to 4) were included in this study. Oxygen kinetics during 6MWT were modeled using nonlinear regression. Three statistical approaches (mixed-effects, meta-analysis and weighted regression) were compared in order to summarize estimates obtained from multiple kinetics. The recovery phase was modeled using 3 distinct equations (log-logistic, Weibull 1 and Weibull 2). Three models were fitted to the set of 61 kinetics. A significant model-averaged difference of 40.39 sec (SE = 17.1) in the time to half decrease of [Formula: see text] level ([Formula: see text]) was found between stage 2 and 4 (p = 0.0178). In addition, the Weibull 1 model characterized by a steeper decrease at the beginning of the recovery phase showed some improvement of goodness of fit when fitted to the kinetics of patients with stage 2 COPD in comparison with the 2 other models. Multimodel inference was successfully used to model [Formula: see text] recovery after 6MWT in patients with COPD. Significant model-averaged differences in [Formula: see text] were found between moderate and very severe COPD patients. Furthermore, specific patterns of [Formula: see text] recovery could be identified across COPD stages.

Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia: A Danish Nationwide Cohort Study.

BACKGROUND: High-risk human papillomavirus (HPV) is essential for developing high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal cancer following CIN2 or CIN3 diagnosis. METHODS: In a nationwide cohort study, we followed nearly 2.8 million women born in 1918-1990 who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. The cohort was linked to multiple nationwide registers to obtain information on cancer diagnoses and confounders. Follow-up started when the women reached 18 years, date of immigration, or January 1978, and continued until emigration, death, December 31, 2012, or the date of first diagnosis of anogenital or rectal cancer. RESULTS: Women with a history of CIN2 or CIN3 had higher risks for subsequent anal, vulvar, and vaginal cancer than women with no such history. The relative risks were higher for CIN3 than CIN2. No excess risk was found for rectal cancer. Analyses in which time since first CIN3 was taken into account showed increased relative risks for anal [HR = 4.8; 95% confidence interval (CI), 3.3-7.0], vulvar (HR = 3.2; 95% CI, 2.0-5.3), and vaginal (HR = 5.5; 95% CI, 2.4-12.3) cancers ≥25 years after CIN3 diagnosis. CONCLUSION: Women with a history of CIN2 or CIN3 have a long-term increased relative risk for developing anal, vulvar, and vaginal cancer due to an impaired ability to control a persistent HPV infection. IMPACT: This finding adds to our understanding of the relation between HPV infection and noncervical anogenital cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1090-7. ©2016 AACR.

Casein improves brachial and central aortic diastolic blood pressure in overweight adolescents: a randomised, controlled trial.

Arterial stiffness, blood pressure (BP) and blood lipids may be improved by milk in adults and the effects may be mediated via proteins. However, limited is known about the effects of milk proteins on central aortic BP and no studies have examined the effects in children. Therefore, the present trial examined the effect of milk and milk proteins on brachial and central aortic BP, blood lipids, inflammation and arterial stiffness in overweight adolescents. A randomised controlled trial was conducted in 193 overweight adolescents aged 12-15 years. They were randomly assigned to drink 1 litre of water, skimmed milk, whey or casein for 12 weeks. The milk-based test drinks contained 35 g protein/l. The effects were compared with the water group and a pretest control group consisting of thirty-two of the adolescents followed 12 weeks before the start of the intervention. Outcomes were brachial and central aortic BP, pulse wave velocity and augmentation index, serum C-reactive protein and blood lipids. Brachial and central aortic diastolic BP (DBP) decreased by 2·7% (P = 0·036) and 2·6 % (P = 0·048), respectively, within the casein group and the changes were significantly different from those of the pretest control group (P = 0·040 and P = 0·034, respectively). There was a significant increase in central aortic DBP, and in brachial and central systolic BP in the whey group compared with the water group (P = 0·003, P = 0·009 and P = 0·002, respectively). There were no changes in measures of arterial stiffness or blood lipid concentrations. A high intake of casein improves DBP in overweight adolescents. Thus, casein may be beneficial for younger overweight subjects in terms of reducing the long-term risk of CVD. In contrast, whey protein seems to increase BP compared with drinking water; however, water may be considered an active control group.

Alcohol intake in pregnancy increases the child's risk of atopic dermatitis. the COPSAC prospective birth cohort study of a high risk population.

BACKGROUND: Atopic dermatitis has increased four-fold over the recent decades in developed countries, indicating that changes in environmental factors associated with lifestyle may play an important role in this epidemic. It has been proposed that alcohol consumption may be one contributing risk factor in this development. OBJECTIVE: To analyze the impact of alcohol intake during pregnancy on the development of atopic dermatitis during the first 7 years of life. METHOD: The COPSAC cohort is a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma, followed up for 7 years with scheduled visits every 6 months as well as visits for acute exacerbations of atopic dermatitis. Risk of atopic dermatitis from any alcohol consumption during pregnancy was analyzed as time-to-diagnosis and adjusted for known risk factors. RESULTS: 177 of 411 children developed atopic dermatitis before age 7 years. We found a significant effect of alcohol intake during pregnancy on atopic dermatitis development (HR 1.44, 95% CI 1.05-1.99 p=0.024). This conclusion was unaffected after adjustment for smoking, mother's education and mother's atopic dermatitis. LIMITATIONS: The selection of a high-risk cohort, with all mothers suffering from asthma, and all children having a gestational age above 35 weeks with no congenital abnormality, systemic illness, or history of mechanical ventilation or lower airway infection. CONCLUSION: Alcohol intake by pregnant women with a history of asthma, is significantly associated with an increased risk for the child for developing atopic dermatitis during the first 7 years of life.