Fleshing Out Vulnerability

In the literature on medical ethics, it is generally admitted that vulnerable persons or groups deserve special attention, care or protection. One can define vulnerable persons as those having a greater likelihood of being wronged – that is, of being denied adequate satisfaction of certain legitimate claims. The conjunction of these two points entails what we call the Special Protection Thesis. It asserts that persons with a greater likelihood of being denied adequate satisfaction of their legitimate claims deserve special attention, care or protection. Such a thesis remains vague, however, as long as we do not know what legitimate claims are. This article aims at dispelling this vagueness by exploring what claims we have in relation to health care – thus fleshing out a claim‐based conception of vulnerability. We argue that the Special Protection Thesis must be enriched as follows: If individual or group X has a greater likelihood of being denied adequate satisfaction of some of their legitimate claims to (i) physical integrity, (ii) autonomy, (iii) freedom, (iv) social provision, (v) impartial quality of government, (vi) social bases of self‐respect or (vii) communal belonging, then X deserves special attention, care or protection. With this improved understanding of vulnerability, vulnerability talk in healthcare ethics can escape vagueness and serve as an adequate basis for practice.     

Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

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Phi Index: A New Metric to Test the Flush Early and Avoid the Rush Hypothesis

Optimal escape theory states that animals should counterbalance the costs and benefits of flight when escaping from a potential predator. However, in apparent contradiction with this well-established optimality model, birds and mammals generally initiate escape soon after beginning to monitor an approaching threat, a phenomena codified as the “Flush Early and Avoid the Rush” (FEAR) hypothesis. Typically, the FEAR hypothesis is tested using correlational statistics and is supported when there is a strong relationship between the distance at which an individual first responds behaviorally to an approaching predator (alert distance, AD), and its flight initiation distance (the distance at which it flees the approaching predator, FID). However, such correlational statistics are both inadequate to analyze relationships constrained by an envelope (such as that in the AD-FID relationship) and are sensitive to outliers with high leverage, which can lead one to erroneous conclusions. To overcome these statistical concerns we develop the phi index (Φ), a distribution-free metric to evaluate the goodness of fit of a 1∶1 relationship in a constraint envelope (the prediction of the FEAR hypothesis). Using both simulation and empirical data, we conclude that Φ is superior to traditional correlational analyses because it explicitly tests the FEAR prediction, is robust to outliers, and it controls for the disproportionate influence of observations from large predictor values (caused by the constrained envelope in AD-FID relationship). Importantly, by analyzing the empirical data we corroborate the strong effect that alertness has on flight as stated by the FEAR hypothesis.     

Assisted Suicide in Switzerland: Clarifying Liberties and Claims

Assisting suicide is legal in Switzerland if it is offered without selfish motive to a person with decision‐making capacity. Although the ‘Swiss model’ for suicide assistance has been extensively described in the literature, the formally and informally protected liberties and claims of assistors and recipients of suicide assistance in Switzerland are incompletely captured in the literature. In this article, we describe the package of rights involved in the ‘Swiss model’ using the framework of Hohfeldian rights as modified by Wenar. After outlining this framework, we dissect the rights involved in suicide assistance in Switzerland, and compare it with the situation in England and Germany. Based on this approach, we conclude that in Switzerland, claim rights exist for those requesting suicide assistance, and for those who are considering providing such assistance, even though no entitlements exist toward suicide assistance. We then describe the implementation of the ‘Swiss model’ and difficulties arising within it. Clarifying these issues is important to understand the Swiss situation, to evaluate what features of it may or may not be worth correcting or emulating, and to understand how it can impact requests for suicide assistance in other countries due to ‘suicide tourism’. It is also important to understand exactly what sets Switzerland apart from other countries with different legislations regarding suicide assistance.     

No Viral Association Found in a Set of Differentiated Vulvar Intraepithelial Neoplasia Cases by Human Papillomavirus and Pan-Viral Microarray Testing

Vulvar Intraepithelial Neoplasia (VIN) is the precursor lesion of Vulvar Squamous Cell Carcinoma (VSCC), and the differentiated type (dVIN) is more frequently observed in relation to VSCC. In contrast to usual-type VIN (uVIN), which is related to infection by human papillomavirus (HPV), a germline mutation in the p53 gene is thought to be associated with ~90% of dVIN cases. To date, no infectious agent has been identified in association with dVIN, and studies investigating this possibility have been hindered by the difficulty in accurately diagnosing dVIN from small biopsies. Here, we used immunostaining for p16^ink4a, a biomarker for HPV infection, to study 14 uVIN high-grade VIN and 14 dVIN cases, and to select 10 dVIN cases to broadly screen for all known viruses using a pan-viral microarray platform (ViroChip). All of the uVIN tissue samples, including 8 warty and 6 basaloid cases, showed positivity with the p16^ink4a immunostain. The staining pattern was full-thickness for all except two cases in which positive staining was localized in the lower 1/3 of the epidermis. In contrast, immunostaining for p16^ink4a was negative in all dVIN cases. ViroChip analysis of 10 pure dVIN samples confirmed the absence of human papillomavirus subtypes or any other virus with the exception of a single sample that showed a weak microarray signature to a porcine herpesvirus. Follow-up PCR testing of the sample was negative for herpesvirus, and in-depth metagenomic next-generation sequencing revealed only sequences corresponding to non-pathogenic viral flora and bacterial contamination. In this study, we demonstrated lack of a virus association in 10 dVIN cases. Alternative pathways for carcinogenesis such as the p53 mutation should be considered for investigation of potential treatment options in dVIN.     

New Short Tandem Repeat-Based Molecular Typing Method for Pneumocystis jirovecii Reveals Intrahospital Transmission between Patients from Different Wards

Pneumocystis pneumonia is a severe opportunistic infection in immunocompromised patients caused by the unusual fungus Pneumocystis jirovecii. Transmission is airborne, with both immunocompromised and immunocompetent individuals acting as a reservoir for the fungus. Numerous reports of outbreaks in renal transplant units demonstrate the need for valid genotyping methods to detect transmission of a given genotype. Here, we developed a short tandem repeat (STR)-based molecular typing method for P. jirovecii. We analyzed the P. jirovecii genome and selected six genomic STR markers located on different contigs of the genome. We then tested these markers in 106 P. jirovecii PCR-positive respiratory samples collected between October 2010 and November 2013 from 91 patients with various underlying medical conditions. Unique (one allele per marker) and multiple (more than one allele per marker) genotypes were observed in 34 (32%) and 72 (68%) samples, respectively. A genotype could be assigned to 55 samples (54 patients) and 61 different genotypes were identified in total with a discriminatory power of 0.992. Analysis of the allelic distribution of the six markers and minimum spanning tree analysis of the 61 genotypes identified a specific genotype (Gt21) in our hospital, which may have been transmitted between 10 patients including six renal transplant recipients. Our STR-based molecular typing method is a quick, cheap and reliable approach to genotype Pneumocystis jirovecii in hospital settings and is sensitive enough to detect minor genotypes, thus enabling the study of the transmission and pathophysiology of Pneumocystis pneumonia.     

HvFT1 (VrnH3) drives latitudinal adaptation in Spanish barleys

In barley, three genes are responsible for the vernalization requirement: VrnH1, VrnH2 and VrnH3. The winter growth habit of barley requires the presence of a recessive VrnH1 allele, together with an active VrnH2 allele. The candidate for VrnH3 (HvFT1) has been recently identified, with evidences pointing at a central role in the integration of the vernalization and photoperiod pathways. Functional polymorphisms have been proposed, but experimental evidence of their role on agronomic performance and adaptation is needed. We examined allelic variation at the promoter and intron 1 of the HvFT1 gene in a landrace collection of barley, finding a high diversity level, with its geographic distribution correlated with latitude. Focusing on genotypes with winter alleles in VrnH1 and VrnH2, an association analysis of the four main HvFT1 haplotypes found in the landrace collection detected differences in time to flowering. Landraces with the intron 1 TC allele, prevalent in the south, flowered 6?C7?days earlier than those with the AG allele, under natural conditions. These results were validated in an independent F₂ population. In both data sets, the effect found was similar, but in opposite direction to that described in literature. The polymorphism reported at intron 1 contributes to variation in flowering time under field conditions. We have found that polymorphisms at the promoter also contribute to the effect of the gene on flowering time under field and controlled conditions. The variety of HvFT1 alleles described constitutes an allelic series that may have been a factor in agro-ecological adaptation of barley.