Physiologically-based pharmacokinetic and toxicokinetic models for estimating human exposure to five toxic elements through oral ingestion

Biological monitoring and physiologically-based pharmacokinetic (PBPK) modelling are useful complementary tools in quantifying human exposure to elements in the environment. In this work, we used PBPK models to determine the optimal time for collecting biological samples in a longitudinal study to determine if participants who consumed allotment produce had been exposed to arsenic, cadmium, chromium, nickel or lead. There are a number of PBPK models for these elements published in the literature, which vary in size, complexity and application, given the differences in physiochemical properties of the elements, organs involved in metabolism and exposure pathways affected. We selected PBPK models from the literature to simulate the oral ingestion pathway from consumption of allotment produce. Some models required modification by reducing or removing selected compartments whilst still maintaining their original predictability. The performance of the modified models was evaluated by comparing the predicted urinary and blood elemental levels with experimental data and other model simulations published in the literature. Overall, the model predictions were consistent with literature data (r > 0.7, p < 0.05), and were influential in predicting when samples should be collected. Our results demonstrate the use of mathematical modelling in informing and optimising the design of longitudinal studies

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Marriage and Divorce in Mojolama

Page range: 67-8

Fertility and family planning in Mojolama

vi, 170 p.; 28 cm

Fertility And Family Planning In Mojolama

viii,165 hal,:29cm

Achieving dialogue with children with severe autism in an adaptive multisensory interaction: the MEDIATE project

This paper presents an adaptive physical environment that allows children with severe autism to successfully interact with/nmultimodal stimuli, giving them a sense of control of the interaction and, hence, providing them with a sense of agency. This has been/nan extremely important effort for two main reasons: 1) This user group cannot be typified, hence making the design of an interactive/nsystem to fit all the spectrum of individuals a very complex task; 2) each individual PAS (Person on the Autistic Spectrum) user must be/nable to develop himself within the environment according to his own capacities and potentiality. Qualitative evaluation by psychologists/nshows very good results and sketches an encouraging future for research on these environments

Efficacy and safety of dofetilide and sotalol in patients with hypertrophic cardiomyopathy

Abstract Background Professional society practice guidelines conflict regarding their recommendations of dofetilide (DOF) and sotalol (STL) for treatment of arrhythmias in hypertrophic cardiomyopathy (HCM), and supporting data is sparse. We aim to assess safety and efficacy of DOF and STL on arrhythmias in HCM. Methods This was an observational study of HCM patients treated with DOF or STL for atrial fibrillation (AF) and ventricular arrhythmias (VA). Outcomes of drug discontinuation and arrhythmia recurrence were compared at 1 year and latest follow-up by Kaplan–Meier analysis. Predictors of drug failure were studied using uni- and multi-variable analyses. Drug-related adverse events were quantitated. Results Here we show that of our cohort of 72 patients (54 ± 14 years old, 75% male), 21 were prescribed DOF for AF, 52 STL for AF, and 18 STL for VA. At 1 year, discontinuation and recurrence rates were similar for DOF-AF (38% and 43%) and STL-AF (29% and 44%) groups. Efficacy data was similar at long-term follow-up of 1603 (IQR 994–4131) days, and for STL-VA. Drug inefficacy was the most common reason for discontinuation (28%) followed by side-effects (13%). Incidences of heart failure hospitalization (5%) and mortality (3%) were low. One STL-AF patient developed non-sustained torsades de pointes in the setting of severe pneumonia and acute kidney injury, but there were no other drug-related serious adverse events. Conclusions DOF and STL demonstrate modest efficacy and satisfactory safety when used for AF and VA in HCM patients

Detecting Recent Crop Phenology Dynamics in Corn and Soybean Cropping Systems of Kentucky

Accurate phenological information is essential for monitoring crop development, predicting crop yield, and enhancing resilience to cope with climate change. This study employed a curve-change-based dynamic threshold approach on NDVI (Normalized Differential Vegetation Index) time series to detect the planting and harvesting dates for corn and soybean in Kentucky, a typical climatic transition zone, from 2000 to 2018. We compared satellite-based estimates with ground observations and performed trend analyses of crop phenological stages over the study period to analyze their relationships with climate change and crop yields. Our results showed that corn and soybean planting dates were delayed by 0.01 and 0.07 days/year, respectively. Corn harvesting dates were also delayed at a rate of 0.67 days/year, while advanced soybean harvesting occurred at a rate of 0.05 days/year. The growing season length has increased considerably at a rate of 0.66 days/year for corn and was shortened by 0.12 days/year for soybean. Sensitivity analysis showed that planting dates were more sensitive to the early season temperature, while harvesting dates were significantly correlated with temperature over the entire growing season. In terms of the changing climatic factors, only the increased summer precipitation was statistically related to the delayed corn harvesting dates in Kentucky. Further analysis showed that the increased corn yield was significantly correlated with the delayed harvesting dates (1.37 Bu/acre per day) and extended growing season length (1.67 Bu/acre per day). Our results suggested that seasonal climate change (e.g., summer precipitation) was the main factor influencing crop phenological trends, particularly corn harvesting in Kentucky over the study period. We also highlighted the critical role of changing crop phenology in constraining crop production, which needs further efforts for optimizing crop management practices