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Freiwilligkeit bei Anfragen nach Suizidassistenz
Get PDFZusammenfassung: Freiwilligkeit bezeichnet die Freiheit einer Entscheidung von unzulässiger Einflussnahme oder Druck. Sie ist ein Element der Freiverantwortlichkeit von Entscheidungen über assistierten Suizid und damit ein wichtiger Beurteilungsgegenstand im Umgang mit Anfragen nach Suizidassistenz. Der vorliegende Beitrag widmet sich der Frage, welche Faktoren die Freiwilligkeit von solchen Anfragen potenziell einschränken können. Anhand der medizinethischen Literatur sowie empirischer Studien aus verwandten Kontexten werden u. a. Mitarbeitende im Gesundheitswesen, Sterbehelfer*innen und Angehörige als zentrale Akteure aufgezeigt, die bei Entscheidungen über assistierten Suizid relevant sein können. Mögliche Formen interpersonaler Einflussnahme können Drohungen, Angebote, zwischenmenschliche Beeinflussung und Überredung sein. Zusätzlich stellen strukturelle Rahmenbedingungen – etwa sozioökonomische Notlagen – mögliche Einflussfaktoren auf die Freiwilligkeit dar. Bei der Beurteilung der Freiverantwortlichkeit eines Suizidentschlusses sollte daher systematisch geprüft werden, ob solche Einflussfaktoren vorliegen. Angesichts der bislang geringen empirischen Datenlage bedarf es dringend weiterer Forschung in diesem Bereich. Dies ist auch für die Entwicklung von Leitlinien zur Beurteilung der Freiwilligkeit bei Anfragen nach assistiertem Suizid essenziell
Expanding the genotypic spectrum of combined oxidative phosphorylation deficiency 54
Get PDFBiallelic hypomorphic variants in PRORP cause the rare autosomal recessive disorder combined oxidative phosphorylation deficiency type 54 (COXPD54). COXPD54 encompasses a clinical spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy with developmental delay and epilepsy. Here, we report two new affected individuals with biallelic PRORP variants with clinical features consistent with COXPD54. One individual was homozygous for c.1505G > A p.Arg502Gln, whereas the other was compound heterozygous for c.1510C > T, p.His504Tyr and c.893C > A, p.Ser298Ter (NM_014672.4). In vitro tRNA processing assays revealed decreased mitochondrial 5′ tRNA leader cleavage by human RNase P complex with the two novel missense PRORP metallonuclease domain variants. These data provide further evidence that biallelic PRORP variants disrupt 5’ tRNA leader cleavage and are associated with a pleiotropic phenotype of COXPD54
Modelling evidence-based practice in initial teacher training: effects on teachers’ skills, knowledge and self-efficacy
Get PDFTeacher training often incorporates observable examples of focal teaching practices – models. Yet there is currently little empirical evidence on the effects of modelling. We tested the effects of video models on trainees’ skills, knowledge, and self-efficacy in relation to using an evidence-based teaching technique: retrieval practice. We recruited 89 first-year trainee teachers, gave them a document containing evidence-based guidance on how to use retrieval practice and then collected pre-test data on how well they were able to do this in a classroom simulator scenario. Participants were then randomised them to one of three groups: an active control group in which they restudied the document (no model), a video model of effective practice, or a similar video model annotated with the underpinning theory. We then collected post-test data in a second simulator exercise. Exposure to video models improved participants’ use of retrieval practice methods relative to no model. However, adding the annotation to the models did not yield additional benefits. Models did not improve teachers’ knowledge or self-efficacy. Findings support the theory that incorporating models in initial teacher training can help new teachers make use of evidence-based teaching practices
Reconstructing post‐crisis recovery in the hinterlands of Constantinople: A high‐resolution first‐millennium CE pollen record from Lake Yeniçağa (NW Türkiye)
Get PDFFacing a novel plague pandemic, military invasions, and political–economic transformations, societies of the eastern Roman (Byzantine) empire had to adapt to a variety of pressures and new ways of exploiting their natural environments during the mid‐1st millennium CE. As a result, the rural economy of Anatolia transitioned from the intensive mixed‐farming regime of the Graeco‐Roman era to a more varied medieval agricultural system. We reconstruct here for the first time this transition in a region of Anatolia located close to Constantinople through pollen analysis of a sediment core from Lake Yeniçağa, dated to between ~2300 and ~1200 cal a BP. After discussing data for the Hellenistic–Roman era, we document repeated attempts at the recovery of mixed farming during the 6th to 8th c. CE. These attempts were only successful toward the end of our study period, with the stabilization of the military situation in the region, as is also visible in the written sources that we analyze in parallel in this paper. Crucially, this model of land exploitation was also constrained by the climatic oscillations that reflected its transitional location between the Aegean, Central Anatolian, and Black Sea climate regions. Thus, our study provides a perfect illustration of the interplay between environment and society in relation to the primary production sector (agriculture), in the dynamic context of a strong elite presence in the nearby capital city
Towards an ethics of vigilance in public health
Get PDFPublic health authorities across the globe have reassured members of the public that they are vigilant to the threat of bird flu’s pandemic potential. But they have also made requests of members of the public to play their own role in vigilance mechanisms, most notably requiring poultry farmers to adopt biosecurity measures at their farms. When should vigilance be practised, and under what circumstances are vigilance requests of publics ethically justified? This paper begins by considering the sociological literature on vigilance in public health. In doing so, it discusses the relationship between vigilance, surveillance and other concepts in public health and establishes the need for moral reflection on vigilance as a distinct category in public health ethics. It then considers the requests for vigilance made to poultry farmers during bird flu as an ethical case study, before ending by providing a series of ethical questions that must be answered by government health authorities considering instituting systems of vigilance and making vigilance requests of publics
Developing a method for tracking RNA in live e. coli cells using fluorogenic DNA oligonucleotide probes
Get PDFSuper-resolution microscopy and the development of single molecule Fluorescence In Situ Hybridisation (smFISH) allows detection and localisation of individual molecules inside cells, deciphering intricate mechanistic details of various biological processes. FISH is well established in fixed cells, but there has been limited success in live cells, particularly in bacteria owing to their smaller size and lack of well-defined partitions. We aim to develop an in vivo smFISH technique which uses short single stranded fluorogenic DNA probes which are electroporated into live Escherichia coli. The spatial information from our study can potentially lead to visualising mRNA molecules throughout their lifetime, from transcription to translation to degradation.Our proof of principle target consists of a short plasmid-expressed RNA, that contains six binding sites for the fluorogenic probe. The observed foci can be tracked and exhibit a wide range of behaviour; from immobility to rapidly diffusing spots, with many transitions between these states. A range of fluorogenic probes were tried with their in vivo behaviour characterised.Despite the large proportion of non-specific interactions, it was observed that on a population level the mobility distributions of the tracks vary between the control and test samples. For this reason, it was concluded that the method has some degree of success and improvements to the design are suggested
Young adulthood adiposity in relation to all-cause and cause-specific mortality: a prospective study of 0.5 million Chinese adults
No full textBackground: Obesity is a well-established risk factor for early death, but the exact shapes of associations between young adulthood body mass index (BMI) and mortality in later life were not well characterized.Methods and findings Using data from the prospective China Kadoorie Biobank study of 430,373 participants (~57% being women, with a median follow-up duration of 12 years), Cox regression analysis was performed to yield adjusted hazard ratios (HRs) relating BMI at ~25 years old (BMI 25) with different mortality outcomes including total mortality (n = 36,814), cardiovascular mortality (n = 13,620), cancer mortality (n = 13,394) and respiratory mortality (n = 2929). Mean BMI25 of participants was 21.9 (SD = 2.5) kg/m2 and 1.9% participants were obese at young adulthood (i.e., BMI25 ≥28.0 kg/m2). Independent of baseline BMI, higher BMI25 was associated with much higher levels of blood glucose and diabetes prevalence at baseline. After adjusting for potential confounders e.g., age, smoking, and baseline measured BMI, BMI25 had a strong positive log-linear association with all above-mentioned mortality outcomes, those being obese at young adulthood had a HR of 1.85 (95% CI: 1.75–1.95), 1.85 (1.71–2.00), 1.40 (1.26–1.56) and 2.34 (1.96–2.81), respectively, compared with participants having BMI25 of 18.5–20.0 kg/m2. The association with cancer mortality was more pronounced in men than in women, but no such heterogeneity observed for total, CVD, and respiratory mortality.Conclusions: The observed strong monotonically positive associations between young adulthood BMI and various mortality outcomes, independent of BMI in later life, supporting the need for an early and stringent body weight control to prevent early death
Lipopolysaccharide confinement in the bacterial outer membrane is governed by interactions within the conserved Lipid A anchor
Get PDFThe outer membrane of Gram-negative bacteria is an asymmetric bilayer in which lipopolysaccharide (LPS), the principal component of the outer leaflet, promotes tight packing and ordering of the membrane components that are essential for the barrier and load-bearing functions of this membrane. Lipopolysaccharide mobility is known to be restricted in the outer membrane, but this confinement and the underlying biophysical interactions responsible remain to be fully characterized. Here, we apply a bio-orthogonal strategy for in situ site-specific fluorescent labeling of LPS. Using fluorescence microscopy, we quantify LPS lateral confinement in the outer membrane of Escherichia coli and demonstrate that this confinement is independent of oligosaccharide domain structure. We show that lipopolysaccharide assembles into discrete supramolecular structures, and that restricted lateral mobility arises from a combination of divalent cation-mediated electrostatic interactions in the anionic Lipid A headgroup, and hydrophobic interactions between acyl chains within the lipid milieu. Magnesium cations exert a greater influence than calcium cations on lipopolysaccharide lateral mobility. These traits are conserved across multiple pathogenic bacterial species, irrespective of O-antigen serotype, showing that lipopolysaccharide confinement is a ubiquitous feature of Gram-negative bacteria
Macrocyclic Covalent Encapsulation of a Multi-Resonant Emitter: Understanding and Controlling Interactions in Highly Efficient Deep-Blue OLEDs
Get PDFMulti-resonant thermally activated delayed fluorescence (MR-TADF) emitters have emerged as popular candidates for the development of blue organic light-emitting diodes (OLEDs), offering narrowband emission, high photoluminescence quantum yields (PLQYs), and the ability to upconvert dark triplet states to bright singlet states. However, their planar polycyclic structures promote detrimental intermolecular interactions in the solid-state which diminish the color purity and introduce nonradiative loss pathways. Furthermore, the intrinsic luminescence of many MR-TADF emitters fails to satisfy the stringent color purity standards required for next-generation display technologies. Here, we synthetically address these issues by covalently encapsulating a blue-shifted MR-TADF emitter within a protective macrocyclic ring. We identify a previously undiscovered utility of macrocyclic encapsulation, whereby it can shield the MR core from the surrounding environment to enhance its radiative rate, PLQY, and reverse intersystem crossing (RISC) efficiency. Only with spectrally resolved transient photoluminescence measurements were we able to identify the weakly emissive aggregate and excimer species, and definitively confirm that the macrocycle suppresses their formation in the solid-state, thereby preserving narrowband deep-blue emission and reducing nonradiative losses. Notably, these performance enhancements were achieved without compromising thermal stability or vacuum-processability. When integrated into an OLED device based on the “hyperfluorescent” strategy, this emitter delivers an exceptional combined maximum external quantum efficiency (EQE) of 33% and (0.146, 0.046) CIE x, y coordinates with peak emission at 451 nm, satisfying BT.2020 blue color requirement, and significantly outperforming its nonencapsulated analogue. This material represents one of the highest efficiency deep-blue OLEDs to date and therefore establishes macrocyclic encapsulation as a powerful synthetic strategy for unlocking the full potential of MR-TADF materials for next-generation OLEDs
Evaluation of the Bangkok Health Research and Ethics Interest Group: reflecting on the experiences of group members, researchers and facilitators participating in an urban community advisory board in Thailand
Get PDFBackground: The Mahidol Oxford Tropical Medicine Research Unit (MORU), headquartered in Bangkok, conducts research on tropical medicine and global health. MORU works closely with a network of community advisory boards (CABs), with members drawn from communities served by its research sites. In 2019, we set up the Bangkok Health Research and Ethics Interest Group (HREIG). HREIG is an urban CAB composed of Bangkok residents from all walks of life who have an interest in health research, but do not have a professional health research background. HREIG advises on clinical research and broader societal issues, complementing MORU’s rural CABs in areas such as the Thai-Myanmar border and northern Cambodia. In 2022, the group had 14 members aged between 22 and 51. Initially, meetings were held in person and in English, to support discussion with international researchers. During COVID-19 restrictions, meetings moved online and adopted Thai as the main language. Main text: To evaluate the group’s first two years, we conducted a mixed-methods study using focus group discussions and anonymous online surveys with group members, researchers and facilitators. We found that members joined to contribute to research and society, and for personal benefits such as learning about health research or meeting new people. While some valued practicing English, it made harder for members to contribute equally, and even those with good conversational English struggled with technical terms. Researchers reported that engaging with the group helped improve their communication skills, and that they valued hearing lay perspectives. Facilitators strengthened their skills in areas such as facilitation, online collaboration, and explaining research in lay terms. As HREIG is not tied to a specific study, its contributions have ranged from improving malaria messaging for the Thai public to testing COVID-19 surveys, or sharing opinions on vaccines and clinical trial participation. Conclusion: Our findings offer in-depth insights into the experiences of HREIG members, researchers and facilitators. We share the outcomes of the group’s activities, and the lessons learnt from running a CAB in an international research environment. We hope that our findings will help others who would like to set up a CAB in a similar context