'Assisted dying' as a comforting heteronomy: the rejection of self-administration in the purported act of self-determination.

'Assisted dying' (an umbrella term for euthanasia and/or assisted suicide) is frequently defended as an act of autonomous self-determination in death but, given a choice, between 93.3% and 100% of patients are reluctant to self-administer (median 99.5%). If required to self-administer, fewer patients request assisted death and, of these, a sizable proportion do not self-administer but die of natural causes. This manifest avoidance runs counter to the concept of autonomous self-determination, even on the supposition that suicide could truly be autonomous. The avoidance of self-administration does not show that self-administration, when it occurs, is necessarily autonomous. It suggests, rather, that there are other frames by which assisted dying is being understood. One such is desire for medical control, a desire shared by patients and doctors. Such a frame is not directed towards an exacting autonomy (self-directed action by the patient) but towards a comforting heteronomy (letting the doctor take control).

Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases.

Cat Eye Syndrome (CES) is a rare genetic disease caused by the presence of a small supernumerary marker chromosome derived from chromosome 22, which results in a partial tetrasomy of 22p-22q11.21. CES is classically defined by association of iris coloboma, anal atresia, and preauricular tags or pits, with high clinical and genetic heterogeneity. We conducted an international retrospective study of patients carrying genomic gain in the 22q11.21 chromosomal region upstream from LCR22-A identified using FISH, MLPA, and/or array-CGH. We report a cohort of 43 CES cases. We highlight that the clinical triad represents no more than 50% of cases. However, only 16% of CES patients presented with the three signs of the triad and 9% not present any of these three signs. We also highlight the importance of other impairments: cardiac anomalies are one of the major signs of CES (51% of cases), and high frequency of intellectual disability (47%). Ocular motility defects (45%), abdominal malformations (44%), ophthalmologic malformations (35%), and genitourinary tract defects (32%) are other frequent clinical features. We observed that sSMC is the most frequent chromosomal anomaly (91%) and we highlight the high prevalence of mosaic cases (40%) and the unexpectedly high prevalence of parental transmission of sSMC (23%). Most often, the transmitting parent has mild or absent features and carries the mosaic marker at a very low rate (<10%). These data allow us to better delineate the clinical phenotype associated with CES, which must be taken into account in the cytogenetic testing for this syndrome. These findings draw attention to the need for genetic counseling and the risk of recurrence.

Assessing effectiveness of braille and audio-tactile performance technique in improving oral hygiene status of young adults with visual impairment.

INTRODUCTION: Young adults with Visual impairment (VI) challenge the dentists' skills and knowledge due to a higher risk of developing oral diseases due to difficulty in attaining good oral hygiene (OH). AIMS: To assess the effectiveness of ATP (Audio-Tactile Performance) technique and braille versus braille alone in improving OH status of young adults with VI. METHODS AND MATERIAL: A parallel arm, randomized controlled trial was conducted among 70 young adults with VI. Participants were randomly allocated to either test group (braille combined with ATP) or control group (braille alone). A pre-validated braille questionnaire was used to obtain the baseline data followed by clinical examination. OH status assessment was recorded through Gingival Index (GI) and Plaque Index (PI) proforma followed by a thorough ultrasonic oral prophylaxis. Periodic reinforcement was carried out on the 7th day, after 1 month and 3 months. The outcomes were assessed at the end of 3rd and 6th month. RESULTS: There was an increase in the knowledge scores after 3 and 6 months and attitude scores, GI scores and PI scores after 6 months in the test group compared to the control group and this difference was found to be statistically significant. CONCLUSIONS: The findings of this study showed that a combination of ATP and braille proved to be more effective than braille alone in improving the knowledge and OH status of young adults with VI.

Passengers' self-protective intentions while using ride-hailing services during the COVID-19 pandemic.

In the transport context, there has been limited research examining passengers' health-protective behaviour while travelling during a health-related crisis such as COVID-19. This study develops a conceptual model aiming to explore determinants associated with passengers' self-protective intentions using the context of ride-hailing services in Vietnam. Ride-hailing services are popular in countries where public transport is underdeveloped. The conceptual model is based on perceived risk and self-efficacy as the main predictor of self-protective intentions when using ride-hailing services. In addition, the proposed conceptual model explores the direct and indirect impact of subjective knowledge and the perceived effectiveness of preventive measures on self-protective intentions. The proposed conceptual model was tested on a large sample of ride-hailing users in Vietnam (n = 527). The structural equation modelling (SEM) analysis results indicate that self-efficacy has the highest total impact on self-protective behaviour, followed by subject knowledge and perceived effectiveness of preventive measures. Self-efficacy also plays a fully mediating role in the linkage between the perceived effectiveness of preventive measures implemented by ride-hailing organisations and the intention to engage in self-protective behaviour. The results of this study expand the current understanding of ride-hailing passengers' health-protective behaviour and contribute to the transport and public health literature.

Exposure of the Calcaneus in the Sinus Tarsi Approach Versus the Lateral Extensile Approach: A Cadaveric Study.

BACKGROUND: The lateral extensile approach (LEA) is an operative approach for calcaneal fractures. High rates of wound complications have led to alternative approaches such as the sinus tarsi approach to grow in popularity. The LEA affords substantial visualization of the calcaneus. This visualization has never been compared in a quantitative manner with the sinus tarsi approach (STA). We aim to quantify the calcaneal visualization afforded by STA and LEA. METHODS: Seven pair-matched, fresh-frozen, below-knee cadaver extremities were included. For each pair, one side received an LEA and the other side received an STA. RESULTS: There were no statistically significant differences in the articular surfaces accessible between the 2 approaches. The total calcaneal surface area accessible was 3107.08 mm2 for LEA and 1444.19 mm2 for STA (P = .02). The LEA allowed better exposure to the lateral wall (P = .01) and the dorsal tuberosity of the calcaneus (P = .04). CONCLUSION: The STA allows for equivalent articular surface exposure when compared with the LEA. Although LEA allows for greater exposure of the lateral wall and dorsal tuberosity, direct visualization of these structures may not warrant the higher risk of wound complications. Surgeons should consider these differences when choosing an operative approach in the treatment of calcaneal fractures.Level III.

Performer Roles and Behaviors in Dyadic Sexually Explicit Media Featuring Men Who Have Sex with Men.

Heterosexual gender roles are not directly relevant to gay romantic relationships, but gay men often take on different relationship roles depending on their sexual roles. In the present paper, we argue that gay men might draw on sexually explicit media (SEM) featuring men who have sex with men (MSM) to get information about how insertive sexual partners ("tops") and receptive sexual partners ("bottoms") typically behave. For this to be the case, however, we would have to reliably observe different behavior in SEM performers acting as tops vs. bottoms. We examined 220 of the most viewed online dyadic MSM SEM videos to determine whether performed verbal and physical intimacy, victimization, and sexual behaviors depended on the sexual role taken. We found that tops and bottoms engaged in similar amounts of intimacy behaviors, but that bottoms were depicted as initiating sexual activity more than tops. Tops enacted physical and psychological victimization more than bottoms, although these behaviors were rare. Tops were shown taking the insertive role across all sexual acts and versatile performers (i.e., those taking both insertive and receptive roles) were rarely depicted. The present study adds to the literature about the complexity of sexual-self-labels, and suggests that MSM SEM depictions of intimacy and sexual decision-making depend on the sexual role taken.

Legal Challenges to Restrictions on Assistance in Suicide in Italy, Germany and Austria: An Ethico-Legal Analysis.

This paper deals with a series of legal cases in Italy, Germany, and Austria, between September 2019 and December 2020, which ruled that laws prohibiting or restricting assistance in suicide were unconstitutional. There are similarities between these three cases, all of which are influenced by the practice of assisted suicide in Switzerland, but also differences, not least because of the antecedent legal contexts. Each case is based on flawed reasoning. They have in common an exaggerated account of autonomy or self-determination, insufficiently qualified by the duty to protect human life or by other ethical constraints. The Italian and Austrian Courts also appeal to the principle of equality and to a supposed analogy with refusal of life-sustaining treatments, both of which raise concerns in relation to further expansion of the provisions. In responding to these flawed judgements, legislators should favour proposals that prevent the normalisation of assisted and non-assisted suicide.

Understanding sexual activity while driving as a form of distracted driving.

Sexual activity while driving has been reported in emerging research. Sexual activity while driving is a form of distracted driving because it includes an individual (the driver) who deviates resources from the primary task (driving) towards a secondary task (sexual activity). However, most of our current knowledge about the range of sexual activities while driving is based on self-reported data or media reports. Thus, an in-depth understanding of sexual activities while driving and their interactions with non-sexual driving behaviours and vehicle control is missing. Additionally, there is limited information on the context of where sexual activities while driving occurs and the influence of factors such as the environment, the vehicle, interactions with other road users, and other in-vehicle distractions. To cover this gap, a content analysis of sexually explicit media (SEM) was conducted on a sample of 270 videos depicting real driving. We conducted descriptive analyses and used decision tree analysis to explore the association between sexual activities while driving and their interactions with non-sexual driving behaviours and vehicle control. The videos portrayed a naturalistic driving situation of a driver of a moving vehicle engaging in sexual activity. The results show that when engaging in sexual activity, drivers do not present safe vehicle control. Sexual activity imposes additional cognitive, physical, and visual demands on the driver, thereby decreasing safety. Similar to other distractions, drivers engaging in sexual activity while driving appear to mitigate risks. Concerning the potential for legal sanctions, it appears that drivers may attempt to conceal sexual activity by reducing their visible nudity and minimising interactions with other road users. Finally, mobile phones and cameras appear to interact with sexual activities while driving, by imposing potential restrictions on the range of sexual activities. Implications for policymakers and practitioners are discussed.

Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder.

PURPOSE: DYRK1A syndrome is among the most frequent monogenic forms of intellectual disability (ID). We refined the molecular and clinical description of this disorder and developed tools to improve interpretation of missense variants, which remains a major challenge in human genetics. METHODS: We reported clinical and molecular data for 50 individuals with ID harboring DYRK1A variants and developed (1) a specific DYRK1A clinical score; (2) amino acid conservation data generated from 100 DYRK1A sequences across different taxa; (3) in vitro overexpression assays to study level, cellular localization, and kinase activity of DYRK1A mutant proteins; and (4) a specific blood DNA methylation signature. RESULTS: This integrative approach was successful to reclassify several variants as pathogenic. However, we questioned the involvement of some others, such as p.Thr588Asn, still reported as likely pathogenic, and showed it does not cause an obvious phenotype in mice. CONCLUSION: Our study demonstrated the need for caution when interpreting variants in DYRK1A, even those occurring de novo. The tools developed will be useful to interpret accurately the variants identified in the future in this gene.

Intimacy in Dyadic Sexually Explicit Media Featuring Men Who Have Sex with Men.

Sexually explicit material (SEM) featuring men who have sex with men (MSM) may be a source of information about intimacy in same-sex male relationships for MSM. However, little is known about how MSM SEM depicts intimacy between male performers. The current study examined the 220 most viewed dyadic scenes of MSM SEM videos for the presence of verbal intimacy (compliments, personal disclosure, and expressions of care) and physical intimacy (kissing, cuddling, affectionate touch, and genital touch before and after sex) between performers. At least one example of physical and verbal intimacy was present in the majority of videos (91% and 68% of videos, respectively). Most forms of physical and verbal intimacy occurred before or during sex, with intimacy being least evident post-sex. We also tested if the presence of intimacy was associated with viewer interactions with videos (likes and dislikes) and number of views. Only one of seven forms of intimacy, care (verbal), was associated with more interactions (i.e., likes and dislikes per 100,000 views), and there was no association with the number of views. Potential implications for MSM's understandings of intimacy are recognized and discussed with reference to sexual script theory.

Construct validation of the Narcissistic Admiration and Rivalry Questionnaire in Spanish-speaking countries: Assessment of the reliability, structural and external validity and cross-cultural equivalence.

A recent re-operationalisation of grandiose narcissism has resulted in the distinction of two narcissistic strategies based on the cognitive, affective-motivational and behavioural dynamics: admiration (assertive self-enhancement) and rivalry (antagonistic self-protection). The Narcissistic Admiration and Rivalry Questionnaire (NARQ) was developed to assess this model with two higher-order dimensions. However, cross-validations of the NARQ have not been extensively conducted across diverse population groups and languages. This study aimed to test the internal and external validity (through the relation with envy and self-esteem), reliability and cross-cultural equivalence of the Spanish version of the NARQ. The psychometric properties were evaluated in a Spanish sample (N = 310), and cross-cultural equivalence was tested in participants from Chile (N = 234) and Colombia (N = 256). The results supported the reliability and validity of the Spanish NARQ, as well as the cross-cultural equivalence across Spanish-speaking countries. In addition, we discuss obtained differences across Spanish, Chilean and Colombian sample within two narcissistic strategies.

Erratum: Author Correction: A framework to identify contributing genes in patients with Phelan-McDermid syndrome.

[This corrects the article DOI: 10.1038/s41525-017-0035-2.].

Deciphering the complexity of the 4q and 10q subtelomeres by molecular combing in healthy individuals and patients with facioscapulohumeral dystrophy.

BACKGROUND: Subtelomeres are variable regions between telomeres and chromosomal-specific regions. One of the most studied pathologies linked to subtelomeric imbalance is facioscapulohumeral dystrophy (FSHD). In most cases, this disease involves shortening of an array of D4Z4 macrosatellite elements at the 4q35 locus. The disease also segregates with a specific A-type haplotype containing a degenerated polyadenylation signal distal to the last repeat followed by a repetitive array of ß-satellite elements. This classification applies to most patients with FSHD. A subset of patients called FSHD2 escapes this definition and carries a mutation in the SMCHD1 gene. We also recently described patients carrying a complex rearrangement consisting of a cis-duplication of the distal 4q35 locus identified by molecular combing. METHODS: Using this high-resolution technology, we further investigated the organisation of the 4q35 region linked to the disease and the 10q26 locus presenting with 98% of homology in controls and patients. RESULTS: Our analyses reveal a broad variability in size of the different elements composing these loci highlighting the complexity of these subtelomeres and the difficulty for genomic assembly. Out of the 1029 DNA samples analysed in our centre in the last 7 years, we also identified 54 cases clinically diagnosed with FSHD carrying complex genotypes. This includes mosaic patients, patients with deletions of the proximal 4q region and 23 cases with an atypical chromosome 10 pattern, infrequently found in the control population and never reported before. CONCLUSION: Overall, this work underlines the complexity of these loci challenging the diagnosis and genetic counselling for this disease.

Problematic Use of Mobile Phones in Australia Is It Getting Worse?

Rapid technological innovations over the past few years have led to dramatic changes in today's mobile phone technology. While such changes can improve the quality of life of its users, problematic mobile phone use can result in its users experiencing a range of negative outcomes such as anxiety or, in some cases, engagement in unsafe behaviors with serious health and safety implications such as mobile phone distracted driving. The aims of the present study are two-fold. First, this study investigated the current problem mobile phone use in Australia and its potential implications for road safety. Second, based on the changing nature and pervasiveness of mobile phones in Australian society, this study compared data from 2005 with data collected in 2018 to identify trends in problem mobile phone use in Australia. As predicted, the results demonstrated that problem mobile phone use in Australia increased from the first data collected in 2005. In addition, meaningful differences were found between gender and age groups in this study, with females and users in the 18-25 year-old age group showing higher mean Mobile Phone Problem Use Scale (MPPUS) scores. Additionally, problematic mobile phone use was linked with mobile phone use while driving. Specifically, participants who reported high levels of problem mobile phone use, also reported handheld and hands-free mobile phone use while driving.

Duplication of 10q24 locus: broadening the clinical and radiological spectrum.

Split-hand-split-foot malformation (SHFM) is a rare condition that occurs in 1 in 8500-25,000 newborns and accounts for 15% of all limb reduction defects. SHFM is heterogeneous and can be isolated, associated with other malformations, or syndromic. The mode of inheritance is mostly autosomal dominant with incomplete penetrance, but can be X-linked or autosomal recessive. Seven loci are currently known: SHFM1 at 7q21.2q22.1 (DLX5 gene), SHFM2 at Xq26, SHFM3 at 10q24q25, SHFM4 at 3q27 (TP63 gene), SHFM5 at 2q31 and SHFM6 as a result of variants in WNT10B (chromosome 12q13). Duplications at 17p13.3 are seen in SHFM when isolated or associated with long bone deficiency. Tandem genomic duplications at chromosome 10q24 involving at least the DACTYLIN gene are associated with SHFM3. No point variant in any of the genes residing within the region has been identified so far, but duplication of exon 1 of the BTRC gene may explain the phenotype, with likely complex alterations of gene regulation mechanisms that would impair limb morphogenesis. We report on 32 new index cases identified by array-CGH and/or by qPCR, including some prenatal ones, leading to termination for the most severe. Twenty-two cases were presenting with SHFM and 7 with monodactyly only. Three had an overlapping phenotype. Additional findings were identified in 5 (renal dysplasia, cutis aplasia, hypogonadism and agenesis of corpus callosum with hydrocephalus). We present their clinical and radiological findings and review the literature on this rearrangement that seems to be one of the most frequent cause of SHFM.

Infant Male Circumcision: A Catholic Theological and Bioethical Analysis.

Infant male circumcision (IMC) has become controversial among Catholics, and many have criticized the practice of routine IMC, still widely performed in the United States. Others have gone further, claiming that circumcision has been condemned explicitly by the Church and criticizing IMC as "mutilation" and, hence, prohibited implicitly by Catholic moral principles. However, closer examination of the Catholic tradition shows that the Church regards IMC as having been a means of grace under the Old Covenant and, more importantly, in the flesh of Jesus. This positive theological account of IMC cannot be evaded by invoking a supposed historical distinction between milah (a token cut) and periah (the complete removal of the foreskin). The Church has never condemned IMC as mutilation, and while IMC carries some risk, there is no evidence that it inflicts per se disabling mutilation. A reasonable body of medical opinion regards IMC as conferring net health benefits. Summary: This paper concerns the ethics of infant male circumcision especially, though not only, as this is practiced within contemporary Judaism. This topic is examined from a Catholic ethical and theological perspective. It is found that the Church has never sought to restrict Jews from practicing circumcision and has never condemned circumcision as "mutilation." Current evidence suggests that infant male circumcision confers net health benefits. Catholic theology since the Second Vatican Council has increasingly emphasized that God's covenant with the Jewish people remains valid. It has never been revoked. This covenant includes infant male circumcision.

Further delineation of the MECP2 duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features.

The Xq28 duplication involving the MECP2 gene (MECP2 duplication) has been mainly described in male patients with severe developmental delay (DD) associated with spasticity, stereotypic movements and recurrent infections. Nevertheless, only a few series have been published. We aimed to better describe the phenotype of this condition, with a focus on morphological and neurological features. Through a national collaborative study, we report a large French series of 59 affected males with interstitial MECP2 duplication. Most of the patients (93%) shared similar facial features, which evolved with age (midface hypoplasia, narrow and prominent nasal bridge, thick lower lip, large prominent ears), thick hair, livedo of the limbs, tapered fingers, small feet and vasomotor troubles. Early hypotonia and global DD were constant, with 21% of patients unable to walk. In patients able to stand, lower limbs weakness and spasticity led to a singular standing habitus: flexion of the knees, broad-based stance with pseudo-ataxic gait. Scoliosis was frequent (53%), such as divergent strabismus (76%) and hypermetropia (54%), stereotypic movements (89%), without obvious social withdrawal and decreased pain sensitivity (78%). Most of the patients did not develop expressive language, 35% saying few words. Epilepsy was frequent (59%), with a mean onset around 7.4 years of age, and often (62%) drug-resistant. Other medical issues were frequent: constipation (78%), and recurrent infections (89%), mainly lung. We delineate the clinical phenotype of MECP2 duplication syndrome in a large series of 59 males. Pulmonary hypertension appeared as a cause of early death in these patients, advocating its screening early in life.

Familial autosomal dominant severe ankyloglossia with tooth abnormalities.

Ankyloglossia is a congenital oral anomaly characterized by the presence of a hypertrophic and short lingual frenulum. Mutations in the gene encoding the transcription factor TBX22 have been involved in isolated ankyloglossia and X-linked cleft palate. The knockout of Lgr5 in mice results in ankyloglossia. Here, we report a five-generation family including patients with severe ankyloglossia and missing lower central incisors. Two members of this family also exhibited congenital anorectal malformations. In this report, male-to-male transmission was in favor of an autosomal dominant inheritance, which allowed us to exclude the X-linked TBX22 gene. Linkage analysis using short tandem repeat markers located in the vicinity of LGR5 excluded this gene as a potential candidate. These results indicate genetic heterogeneity for ankyloglossia. Further investigations with additional families are required in order to identify novel candidate genes.

A framework to identify contributing genes in patients with Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is characterized by a variety of clinical symptoms with heterogeneous degrees of severity, including intellectual disability (ID), absent or delayed speech, and autism spectrum disorders (ASD). It results from a deletion of the distal part of chromosome 22q13 that in most cases includes the SHANK3 gene. SHANK3 is considered a major gene for PMS, but the factors that modulate the severity of the syndrome remain largely unknown. In this study, we investigated 85 patients with different 22q13 rearrangements (78 deletions and 7 duplications). We first explored the clinical features associated with PMS, and provide evidence for frequent corpus callosum abnormalities in 28% of 35 patients with brain imaging data. We then mapped several candidate genomic regions at the 22q13 region associated with high risk of clinical features, and suggest a second locus at 22q13 associated with absence of speech. Finally, in some cases, we identified additional clinically relevant copy-number variants (CNVs) at loci associated with ASD, such as 16p11.2 and 15q11q13, which could modulate the severity of the syndrome. We also report an inherited SHANK3 deletion transmitted to five affected daughters by a mother without ID nor ASD, suggesting that some individuals could compensate for such mutations. In summary, we shed light on the genotype-phenotype relationship of patients with PMS, a step towards the identification of compensatory mechanisms for a better prognosis and possibly treatments of patients with neurodevelopmental disorders.

Barber-Say Syndrome and Ablepharon-Macrostomia Syndrome: A Patient's View.

Barber-Say syndrome (BSS) and ablepharon-macrostomia syndrome (AMS) are infrequently reported congenital malformation disorders caused by mutations in the TWIST2 gene. Both are characterized by abnormalities in ectoderm-derived structures and cause a very unusual morphology of mainly the face in individuals with otherwise normal cognition and normal physical functioning. We studied the impact that the presence of BSS and AMS has on psychosocial functioning of affected individuals and their families, using their point of view to start with. We tabulated frequently asked questions from affected individuals and families, and a parent of an affected child and an affected adult woman offered personal testimonies. We focused on perception of illness, body satisfaction, and the consequences for an otherwise normal individual who has a disorder that interferes with body image. The importance of paying particular attention to the management of both the physical appearance and the consequences of these entities on the quality of life is stressed by the affected individuals themselves.