Whatever works: Uncertainty and technological hybrids in medical innovation

The persistent uncertainty that looms over the search for solutions to health problems offers important conceptual insights for the study of technological change. This paper explores the notion of hybridization, namely the embodiment of multiple competing operational principles within a single medical device, as strategy to deal with the practical shortcomings due to said uncertainty. The history of the development of the hybrid artificial disc affords the elaboration of an alternative view of hybridization and, at the same time, the articulation of a dualism between medical science as area of basic research (e.g. what disease is) and as practical knowledge (e.g. how disease can be tackled).Barberá Tomás, JD.; Consoli, D. (2012). Whatever works: Uncertainty and technological hybrids in medical innovation. Technological Forecasting and Social Change. 79(5):932-948. doi:10.1016/j.techfore.2011.12.009S93294879

DNA methylation and body mass index from birth to adolescence : meta-analyses of epigenome-wide association studies

Background DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P <1.06 x 10(-7), with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P-enrichment = 1; childhood P-enrichment = 2.00 x 10(-4); adolescence P-enrichment = 2.10 x 10(-7)). Conclusions There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.Peer reviewe

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

Duke University Medical Center Honors the 65th General Hospital World War II

Dedication ceremony for the sculpture honoring the 65th General Hospital reserve unit; held October 26, 200

Cardiopulmonary effects of pressure breathing during hypothermia /

Continuous pressure breathing was studied in hypothermic anesthetized dogs. Alveolar ventilation decreased during continuous positive pressure breathing (CPPB) and increased during continuous negative pressure breathing (CNPB). The changes in alveolar ventilation were due to changes in respiratory rate as well as in respiratory dead space. Cardiac output fell significantly during CPPB due to a reduction in heart rate and stroke volume. During CNPB cardiac output was only slightly greater than during control as a result of a fall in heart rate and an increase in stroke volume. Oxygen consumption was reduced to 60% of control during CPPB of 16 cm H2O, but was 25% greater than control during CNPB. Qualitatively, CO2 production changed as did O2 consumption, but was different quantitatively during CNPB, indicating hyperventilation due to increased respiratory rate. Mean pulmonary artery pressures and pulmonary resistance varied directly with the applied intratracheal pressure. The results indicate that the hypothermic animal can tolerate an imposed stress such as CPPB and can increase its O2 consumption during CNPB as does the normothermic animal. (Author)."April 1967."Includes bibliographic references (page 15).Continuous pressure breathing was studied in hypothermic anesthetized dogs. Alveolar ventilation decreased during continuous positive pressure breathing (CPPB) and increased during continuous negative pressure breathing (CNPB). The changes in alveolar ventilation were due to changes in respiratory rate as well as in respiratory dead space. Cardiac output fell significantly during CPPB due to a reduction in heart rate and stroke volume. During CNPB cardiac output was only slightly greater than during control as a result of a fall in heart rate and an increase in stroke volume. Oxygen consumption was reduced to 60% of control during CPPB of 16 cm H2O, but was 25% greater than control during CNPB. Qualitatively, CO2 production changed as did O2 consumption, but was different quantitatively during CNPB, indicating hyperventilation due to increased respiratory rate. Mean pulmonary artery pressures and pulmonary resistance varied directly with the applied intratracheal pressure. The results indicate that the hypothermic animal can tolerate an imposed stress such as CPPB and can increase its O2 consumption during CNPB as does the normothermic animal. (Author).Research supported by Aerospace Medical Division, Air Force Systems Command, United States Air Force; report prepared by Duke University Medical Center under contract no.Mode of access: Internet