Adverse childhood experiences and incident coronary heart disease: a counterfactual analysis in the Whitehall II prospective cohort study

Objectives: Adverse childhood experience is thought to be associated with risk of coronary heart disease, but it is not clear which experiences are cardiotoxic, and whether risk increases with the accumulation of adverse childhood experiences. Methods: Participants were 5149 adults (72.6% men) in the Whitehall II cohort study. Parental death was recorded at phase 1 (median age in years 44.3), and 13 other adverse childhood experiences at phase 5 (55.3). We applied Cox proportional hazards regression with person-time from phase 5 to examine associations of adverse childhood experiences with incident coronary heart disease. We predicted hazard ratios according to count of the experiences, and examined dose-response effect. We finally estimated reduction of coronary heart disease in a hypothetical scenario, the absence of adverse childhood experiences. Results: Among study participants, 62.9% had at least one adversity, with “financial problems” having the highest prevalence (26.1%). There were 509 first episodes of coronary heart disease during an average 12.9 years follow-up. Among 14 adverse childhood experiences in a multiply adjusted model, “parental unemployment” showed the highest hazard of coronary heart disease incidence (hazard ratio; 95% confidence interval: 1.53; 1.16 to 2.02). No dose-response effect was observed (constant for proportionality in hazard ratio: 1.05, 0.99 to 1.11). Based on the estimates of final model, in the absence of childhood adversities, we estimated a 6.0% reduction in coronary heart disease (0.94; 0.87 to 1.01), but the confidence interval includes one. Conclusion: Although individual adverse childhood experiences show some association with coronary heart disease, there is no clear relationship with the number of adverse experiences. Further research is required to quantify effects of multiple and combinations of adverse childhood experiences considering timing, duration, and severity

Association of aortic stiffness with cognitive decline: Whitehall II longitudinal cohort study

Aortic stiffness is associated with an increased risk of cardio- and cerebrovascular disease and mortality and may increase risk of dementia. The aim of the present study is to examine the association between arterial stiffness and cognitive decline in a large prospective cohort study with three repeated cognitive assessment over 7 years of follow-up. Aortic pulse wave velocity (PWV) was measured among 4300 participants (mean ± standard deviation age 65.1 ± 5.2 years) in 2007–2009 and categorized based on the tertiles: (lowest third:  8.91 m/s). A global cognitive score was calculated in 2007–2009, 2012–2013, and 2015–2016 based on responses to memory, reasoning and fluency tests. Standardized global cognitive score (mean = 0, SD = 1) in highest third versus lowest third of PWV category was lower at baseline (− 0.12, 95% CI − 0.18, − 0.06). Accelerated 7-year cognitive decline was observed among individuals with the highest PWV [difference in 7-year cognitive change for highest third versus lowest third PWV: − 0.06, 95% CI − 0.11, − 0.01, P < 0.01]. Higher aortic stiffness was associated with faster cognitive decline. Clinicians may be able to use arterial stiffness severity as an indicator to administer prompt treatments to prevent or delay the onset of cognitive decline or dementia. Future studies need to determine whether early intervention of vascular stiffness is effective in delaying these outcomes

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub

Improvement in the Accuracy of Back Trajectories Using WRF to Identify Pollen Sources in Southern Iberian Peninsula

Airborne pollen transport at micro-, meso-gamma and meso-beta scales must be studied by atmospheric models, having special relevance in complex terrain. In these cases, the accuracy of these models is mainly determined by the spatial resolution of the underlying meteorological dataset. This work examines how meteorological datasets determine the results obtained from atmospheric transport models used to describe pollen transport in the atmosphere. We investigate the effect of the spatial resolution when computing backward trajectories with the HYSPLIT model. We have used meteorological datasets from the WRF model with 27, 9 and 3 km resolutions and from the GDAS files with 1 ° resolution. This work allows characterizing atmospheric transport of Olea pollen in a region with complex flows. The results show that the complex terrain affects the trajectories and this effect varies with the different meteorological datasets. Overall, the change from GDAS to WRF-ARW inputs improves the analyses with the HYSPLIT model, thereby increasing the understanding the pollen episode. The results indicate that a spatial resolution of at least 9 km is needed to simulate atmospheric flows that are considerable affected by the relief of the landscape. The results suggest that the appropriate meteorological files should be considered when atmospheric models are used to characterize the atmospheric transport of pollen on micro-, meso-gamma and meso-beta scales. Furthermore, at these scales, the results are believed to be generally applicable for related areas such as the description of atmospheric transport of radionuclides or in the definition of nuclear-radioactivity emergency preparedness

Perivascular Spaces Segmentation in Brain MRI Using Optimal 3D Filtering

Perivascular Spaces (PVS) are a recently recognised feature of Small Vessel Disease (SVD), also indicating neuroinflammation, and are an important part of the brain's circulation and glymphatic drainage system. Quantitative analysis of PVS on Magnetic Resonance Images (MRI) is important for understanding their relationship with neurological diseases. In this work, we propose a segmentation technique based on the 3D Frangi filtering for extraction of PVS from MRI. Based on prior knowledge from neuroradiological ratings of PVS, we used ordered logit models to optimise Frangi filter parameters in response to the variability in the scanner's parameters and study protocols. We optimized and validated our proposed models on two independent cohorts, a dementia sample (N=20) and patients who previously had mild to moderate stroke (N=48). Results demonstrate the robustness and generalisability of our segmentation method. Segmentation-based PVS burden estimates correlated with neuroradiological assessments (Spearman's $\rho$ = 0.74, p $<$ 0.001), suggesting the great potential of our proposed metho

Does Poorer Pulmonary Function Accelerate Arterial Stiffening?

Whether poorer pulmonary function accelerates progression of arterial stiffness remains unknown as prior observational studies have not examined longitudinal changes in arterial stiffness in relation to earlier pulmonary function. Data (N=5342, 26% female) were drawn from the Whitehall II cohort study. Participants completed repeated assessments of forced expiratory volume in 1 second (FEV1, L) and carotid-femoral pulse wave velocity (cf-PWV, m/s) over 5 years. The effect of FEV1 on later cf-PWV and its progression was estimated using linear mixed-effects modeling. Possible explanatory mechanisms, such as mediation by low-grade systemic inflammation, common-cause explanation by preexisting cardiometabolic risk factors, and reverse-causation bias, were assessed. Poorer pulmonary function was associated with later higher cf-PWV and its subsequent progression (cf-PWV 5-year change 0.09, 95% CI 0.03-0.17 per SD lower FEV1) after adjustment for age, sex, ethnicity, heart rate, and mean arterial pressure. Decrease in pulmonary function was associated with later higher cf-PWV (0.17, 95% CI 0.04-0.30 in the top compared to bottom quartile of decline in FEV1). There was no evidence to support mediation by circulating CRP (C-reactive protein) or IL (interleukin)-6. Furthermore, arterial stiffness was not associated with later FEV1 after accounting for cardiometabolic status. In conclusion, poorer pulmonary function predicted future arterial stiffness. These findings support pulmonary function as a clinically important risk factor for arterial stiffness and provide justification for future intervention studies for pulmonary function based on its relationship with arterial stiffness

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

Exergo-economic comparison of waste heat recovery cycles for a cement industry case study

José J. Fierro ORCID ID: https://orcid.org/0000-0003-2306-611X; Carlos A. Marenco-Porto ORCID ID: https://orcid.org/0000-0002-2969-5040; César Nieto-Londoño ORCID ID: https://orcid.org/0000-0001-6516-9630; Ana Escudero-Atehortua ORCID ID: https://orcid.org/0000-0003-2962-4426; Hussam Jouhara ORCID ID: https://orcid.org/0000-0002-6910-6116; Luiz C. Wrobel ORCID ID: https://orcid.org/0000-0001-6702-0178.Copyright © 2022 The Authors. This work evaluates the performance regarding exergo-economic and emissions requirements of Waste Heat Recovery configurations (Organic Rankine cycle, Trilateral flash cycle, and Kalina cycle) under different operating conditions and working fluids. It was found that the best economic performance is presented by the Organic Rankine cycle that operates with Cyclo-Pentane and has two intermediate heat exchangers since it pushes the expansion temperature up while allowing a higher heat input to the cycle. As a result, it delivers 6.2 MW with a net present value, the net present value of 0.74 million dollars, saving up to 11480 tonnes of carbon dioxide per year. This performance far exceeds that obtained in the previous work, around 50% higher net-work with 80% higher net present value, and constitutes the best alternative in terms of performance to recover waste heat from the source evaluated. Regarding the Trilateral flash cycle, it can be stated that the net work and the exergetic performance are independent of the working fluid as long as there is not a very large volume change in the expander. The Kalina cycle presents slight exergy destruction, but the power delivered does not compensate for the high total capital cost due to the high pressures that must be handled, 55–120 bar, compared to the Organic Rankine cycle, 4–40 bar. An approach was made to more realistic cases where the methodology used facilitates selecting the best alternative when there is a budget restriction using the total capital cost and net work alternatively like a fixed requirement and net present value as the primary decision criterion.This research is funded by the The Royal Academy of Engineering through the Newton-Caldas Fund IAPP18-19\218 project that provides a framework where industry and academic institutions from Colombia and the UK collaborate in the heat recovery in large industrial systems

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography