Attitudes towards terminal sedation: an empirical survey among experts in the field of medical ethics

BACKGROUND: "Terminal sedation" regarded as the use of sedation in (pre-)terminal patients with treatment-refractory symptoms is controversially discussed not only within palliative medicine. While supporters consider terminal sedation as an indispensable palliative medical treatment option, opponents disapprove of it as "slow euthanasia". Against this background, we interviewed medical ethics experts by questionnaire on the term and the moral acceptance of terminal sedation in order to find out how they think about this topic. We were especially interested in whether experts with a professional medical and nursing background think differently about the topic than experts without this background. METHODS: The survey was carried out by questionnaire; beside the provided answering options free text comments were possible. As test persons we chose the 477 members of the German Academy for Ethics in Medicine, an interdisciplinary society for medical ethics. RESULTS: 281 completed questionnaires were returned (response rate = 59%). The majority of persons without medical background regarded "terminal sedation" as an intentional elimination of consciousness until the patient's death occurs; persons with a medical background generally had a broader understanding of the term, including light or intermittent forms of sedation. 98% of the respondents regarded terminal sedation in dying patients with treatment-refractory physical symptoms as acceptable. Situations in which the dying process has not yet started, in which untreatable mental symptoms are the indication for terminal sedation or in which life-sustaining measures are withdrawn during sedation were evaluated as morally difficult. CONCLUSION: The survey reveals a great need for research and discussion on the medical indication as well as on the moral evaluation of terminal sedation. Prerequisite for this is a more precise terminology which describes the circumstances of the sedation

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

Determination of composition and structure of spongy bone tissue in human head of femur by Raman spectral mapping

Biomechanical properties of bone depend on the composition and organization of collagen fibers. In this study, Raman microspectroscopy was employed to determine the content of mineral and organic constituents and orientation of collagen fibers in spongy bone in the human head of femur at the microstructural level. Changes in composition and structure of trabecula were illustrated using Raman spectral mapping. The polarized Raman spectra permit separate analysis of local variations in orientation and composition. The ratios of ν2PO43−/Amide III, ν4PO43−/Amide III and ν1CO32−/ν2PO43− are used to describe relative amounts of spongy bone components. The ν1PO43−/Amide I ratio is quite susceptible to orientation effect and brings information on collagen fibers orientation. The results presented illustrate the versatility of the Raman method in the study of bone tissue. The study permits better understanding of bone physiology and evaluation of the biomechanical properties of bone

Nasal Airway Obstruction Study (NAIROS): a phase III, open-label, mixed-methods, multicentre randomised controlled trial of septoplasty versus medical management of a septal deviation with nasal obstruction

Background Septoplasty (surgery to straighten a deviation in the nasal septum) is a frequently performed operation worldwide, with approximately 250,000 performed annually in the US and 22,000 in the UK. Most septoplasties aim to improve diurnal and nocturnal nasal obstruction. The evidence base for septoplasty clinical effectiveness is hitherto very limited. Aims To establish, and inform guidance for, the best management strategy for individuals with nasal obstruction associated with a deviated septum. Methods/design A multicentre, mixed-methods, open label, randomised controlled trial of septoplasty versus medical management for adults with a deviated septum and a reduced nasal airway. Eligible patients will have septal deflection visible at nasendoscopy and a nasal symptom score ≥ 30 on the NOSE questionnaire. Surgical treatment comprises septoplasty with or without reduction of the inferior nasal turbinate on the anatomically wider side of the nose. Medical management comprises a nasal saline spray followed by a fluorinated steroid spray daily for six months. The recruitment target is 378 patients, recruited from up to 17 sites across Scotland, England and Wales. Randomisation will be on a 1:1 basis, stratified by gender and severity (NOSE score). Participants will be followed up for 12 months post randomisation. The primary outcome measure is the total SNOT-22 score at 6 months. Clinical and economic outcomes will be modelled against baseline severity (NOSE scale) to inform clinical decision-making. The study includes a recruitment enhancement process, and an economic evaluation. Discussion The NAIROS trial will evaluate the clinical effectiveness and cost-effectiveness of septoplasty versus medical management for adults with a deviated septum and symptoms of nasal blockage. Identifying those individuals most likely to benefit from surgery should enable more efficient and effective clinical decision-making, and avoid unnecessary operations where there is low likelihood of patient benefit

Processing Induced Changes in Food Proteins: Amyloid Formation during Boiling of Hen Egg White

Amyloid fibrils (AFs) are highly ordered protein nanofibers composed of cross β-structure that occur in nature, but that also accumulate in age-related diseases. Amyloid propensity is a generic property of proteins revealed by conditions that destabilize the native state, suggesting that food processing conditions may promote AF formation. This had only been shown for foie gras, but not in common foodstuffs. We here extracted a dense network of fibrillar proteins from commonly consumed boiled hen egg white (EW) using chemical and/or enzymatic treatments. Conversion of EW proteins into AFs during boiling was demonstrated by thioflavin T fluorescence, Congo red staining, and X-ray fiber diffraction measurements. Our data show that cooking converts approximately 1–3% of the protein in EW into AFs, suggesting that they are a common component of the human diet

In vitro mycorrhization of micropropagated plants: studies on Castanea sativa Mill.

In vitro mycorrhization can be made by several axenic and nonaxenic techniques but criticism exists about their artificiality and inability to reproduce under natural conditions. However, artificial mycorrhization under controlled conditions can provide important information about the physiology of symbiosis. Micropropagated Castanea sativa plants were inoculated with the mycorrhizal fungus Pisolithus tinctorius after in vitro rooting. The mycorrhizal process was monitored at regular intervals in order to evaluate the mantle and hartig net formation, and the growth rates of mycorrhizal and nonmycorrhizal plants. Plant roots show fungal hyphae adhesion at the surface after 24 hours of mycorrhizal induction. After 20 days a mantle can be observed and a hartig net is forming although the morphology of the epidermal cells remains unaltered. At 30 days of root–fungus contact the hartig net is well developed and the epidermal cells are already enlarged. After 50 days of mycorrhizal induction, growth was higher for mycorrhizal plants than for nonmycorrhizal ones. The length of the major roots was lower in mycorrhizal plants after 40 days. Fresh and dry weights were higher in mycorrhizal plants after 30 days. The growth rates of chestnut mycorrhizal plants are in agreement with the morphological development of the mycorrhizal structures observed at each mycorrhizal time. The assessment of symbiotic establishment takes into account the formation of a mantle and a hartig net that were already developed at 30 days, when differences between fresh and dry weights of mycorrhizal and nonmycorrhizal plants can be quantified. In vitro conditions, mycorrhization influences plant physiology after 20 days of root–fungus contact, namely in terms of growth rates. Fresh and dry weights, heights, stem diameter and growth rates increased while major root growth rate decreased in mycorrhizal plants.Springe

Computer vision and machine learning for robust phenotyping in genome-wide studies

Traditional evaluation of crop biotic and abiotic stresses are time-consuming and labor-intensive limiting the ability to dissect the genetic basis of quantitative traits. A machine learning (ML)-enabled image-phenotyping pipeline for the genetic studies of abiotic stress iron deficiency chlorosis (IDC) of soybean is reported. IDC classification and severity for an association panel of 461 diverse plant-introduction accessions was evaluated using an end-to-end phenotyping workflow. The workflow consisted of a multi-stage procedure including: (1) optimized protocols for consistent image capture across plant canopies, (2) canopy identification and registration from cluttered backgrounds, (3) extraction of domain expert informed features from the processed images to accurately represent IDC expression, and (4) supervised ML-based classifiers that linked the automatically extracted features with expert-rating equivalent IDC scores. ML-generated phenotypic data were subsequently utilized for the genome-wide association study and genomic prediction. The results illustrate the reliability and advantage of ML-enabled image-phenotyping pipeline by identifying previously reported locus and a novel locus harboring a gene homolog involved in iron acquisition. This study demonstrates a promising path for integrating the phenotyping pipeline into genomic prediction, and provides a systematic framework enabling robust and quicker phenotyping through ground-based systems

Global prospective case series of ERCPs using a single-use duodenoscope

Background The first commercialized single-use duodenoscope was cleared by the US Food and Drug Administration in December 2019. Data regarding endoscopic retrograde cholangiopancreatography (ERCP) using a single-use duodenoscope are needed on a broader range of cases conducted by endoscopists with varying levels of experience in a wide range of geographic areas. Methods 61 endoscopists at 22 academic centers in 11 countries performed ERCP procedures in adult patients aged ? 18. Outcomes included ERCP completion for the intended indication, rate of crossover to a reusable endoscope, device performance ratings, and serious adverse events (SAEs). Results Among 551 patients, 236 (42.8 %) were aged &gt;65, 281 (51.0 %) were men, and 256 (46.5 %) had their procedure as an inpatient. ERCPs included 196 (35.6 %) with American Society for Gastrointestinal Endoscopy complexity of grades 3 4. A total of 529 ERCPs (96.0 %) were completed: 503 (91.3 %) using only the single-use duodenoscope, and 26 (4.7 %) with crossover to a reusable endoscope. There were 22 ERCPs (4.0 %) that were not completed, of which 11 (2.0 %) included a crossover and 11 (2.0 %) were aborted cases (no crossover). Median ERCP completion time was 24.0 minutes. Median overall satisfaction with the single-use duodenoscope was 8.0 (scale of 1 to 10 [best]). SAEs were reported in 43 patients (7.8 %), including 17 (3.1 %) who developed post-ERCP pancreatitis. Conclusions In academic medical centers over a wide geographic distribution, endoscopists with varying levels of experience using the first marketed single-use duodenoscope had good ERCP procedural success and reported high performance ratings for this device.</p