When medical assistance in dying is not a last resort option: survey of the Canadian public.

OBJECTIVES: What are the Canadian public's understanding of and views toward medical assistance in dying (MAID) in persons refusing recommended treatment or lacking access to standard treatment or resources? DESIGN/SETTING: An online survey assessed knowledge of and support for Canadian MAID law, and views about four specific scenarios in a two (medical or psychiatric) by two (treatment refusal or lack of access) design. PARTICIPANTS: A quota sample (N=2140) matched to the 2021 Canadian census by age, gender, income, education and province. MAIN OUTCOMES: Participants' level of support for MAID in general and in the four specific scenarios. RESULTS: Only 12.1% correctly answered ≥4 of 5 knowledge questions about the MAID law; only 19.2% knew terminal illness is not required and 20.2% knew treatment refusal is compatible with eligibility. 73.3% of participants expressed support for the MAID law in general, matching a nationally representative poll that used the same question. 40.4% of respondents supported MAID for mental illnesses. Support for MAID in the scenarios depicting refusal or lack of access to treatment ranged from 23.2% (lack of access in medical condition) to 32.0% (treatment refusal in medical illness). Older age, more education, higher income, lower religious attendance or being white was associated with greater support for MAID in general but was either negatively associated or not associated with support for MAID in the four refusal or lack of access scenarios. CONCLUSIONS: Most Canadians support the current MAID law but appear unaware that MAID cases they do not support are compatible with that law. The lower support for MAID in the four scenarios cuts across sociodemographics. The gap between current policy and public opinion warrants further study. For jurisdictions debating MAID, opinion surveys may need to go beyond assessing general attitudes, and target knowledge and views regarding implications of legalisation.

The conceptual injustice of the brain death standard.

Family disputes over the diagnosis of brain death have caused much controversy in the bioethics literature over the conceptual validity of the brain death standard. Given the tenuous status of brain death as death, it is pragmatically fruitful to reframe intractable debates about the metaphysical nature of brain death as metalinguistic disputes about its conceptual deployment. This new framework leaves the metaphysical debate open and brings into focus the social functions that are served by deploying the concept of brain death. In doing so, it highlights the epistemic injustice of medicolegal authorities that force people to uniformly accept brain death as a diagnosis of death based on normative considerations of institutional interests, such as saving hospital resources and organ supplies, rather than empirical evidence of brain death as death, which is insufficient at best and nonexistent at worst. In light of this injustice, I propose the rejection of the uniform standard of brain death in favor of a choice-based system that respects families' individualized views of death.

Teaching respect for body donors: A US medical student perspective.

Recent controversies over the mismanagement of body donors in US medical schools have raised public concerns over the ethical treatment of bodies in "anatomical gift" programs. Despite widespread moral outrage at such cases, medical students may still make seemingly inconsequential mistakes or jokes that in fact constitute acts of disrespect. This may partially be attributed to the process of desensitization in working with human remains, and indicates a further need to inculcate into medical students the ethical responsibilities of working with body donors. Donation agreement statements that lack specific information about the respectful treatment of bodies in the anatomy laboratory may serve as an additional point of concern for potential donors seeking reassurance about the future treatment of their bodies. This viewpoint draws from the anecdotal experiences of medical students to portray two scenarios of medical students' disrespectful conduct toward body donors, and constructs an account of moral respect for human remains based on respect for posthumous autonomy and respect in attitude. It then provides suggestions for US medical schools to incorporate this ethical framework into their anatomy curricula to instill respectful dispositions in its students and facilitate a more robust informed consent process for potential donors who entrust their bodies to medical students.

Does musicianship influence the perceptual integrality of tones and segmental information?

This study investigated the effect of musicianship on the perceptual integrality of tones and segmental information in non-native speech perception. We tested 112 Cantonese musicians, Cantonese non-musicians, English musicians, and English non-musicians with a modified Thai tone AX discrimination task. In the tone discrimination task, the control block only contained tonal variations, whereas the orthogonal block contained both tonal and task-irrelevant segmental variations. Relative to their own performance in the control block, the Cantonese listeners showed decreased sensitivity index (d') and increased response time in the orthogonal block, reflecting integral perception of tones and segmental information. By contrast, the English listeners performed similarly across the two blocks, indicating independent perception. Bayesian analysis revealed that the Cantonese musicians and the Cantonese non-musicians perceived Thai tones and segmental information equally integrally. Moreover, the English musicians and the English non-musicians showed similar degrees of independent perception. Based on the above results, musicianship does not seem to influence tone-segmental perceptual integrality. While musicianship apparently enhances tone sensitivity, not all musical advantages are transferrable to the language domain.

Why Aren't All Cantonese Tones Equally Confusing to English Listeners?

English listeners often struggle to perceive tones, but some are easier than others. This study examined these phenomena grounded in the feature weighing perspective (FWP) and the Perceptual Assimilation Model for Suprasegmentals (PAM-S). Forty-seven English and Cantonese listeners completed 4,212 trials of Cantonese tone discrimination and sequence recall tasks. The English listeners showed asymmetrical perceptual patterns of discrimination but not sequence recall. Specifically, these English listeners discriminated T1-T5, T3-T5, and T4-T5 more accurately than T1-T4, T3-T4, and T1-T3. However, they recalled the contour tone and level tone sequences with similar accuracies. Results of the discrimination task aligned with the predictions of PAM-S but not FWP. However, results of the sequence recall task did not support PAM-S. Together, these results suggest that PAM-S only applies to simple discrimination, not abstract phonological processing with a high memory load.

What Is "Music" in Music-to-Language Transfer? Musical Ability But Not Musicianship Supports Cantonese Listeners' English Stress Perception.

PURPOSE: This study investigates how Cantonese language experience influences the potential effects of (a) musicianship and (b) musical ability on English stress perception. METHOD: The sample contained 124 participants, evenly split into Cantonese musician, Cantonese nonmusician, English musician, and English nonmusician groups. They completed the English stress discrimination task, English stress sequence recall task, Musical Ear Test, and nonverbal intelligence task. Following the musicianship-based analysis, 44 Cantonese and English listeners were reassigned to four groups based on their musical ability-Cantonese high musical ability, Cantonese low musical ability, English high musical ability, and English low musical ability groups. RESULTS: Musicianship-based analysis on English stress perception revealed a significant interaction between musicianship and language. Specifically, musicians outperformed nonmusicians only among the English but not the Cantonese listeners. By contrast, ability-based analysis showed significant main effects of musical ability and language. For both Cantonese and English listeners, those with a high musical ability outperformed those with a low musical ability. Regardless of musical ability, Cantonese listeners outperformed English listeners. Correlational analyses yielded consistent findings. CONCLUSIONS: This study has found cross-sectional evidence that musical ability, but not musicianship, facilitates Cantonese English as a second language (ESL) listeners' English stress perception. From a theoretical perspective, the current findings motivate two potential additions to the OPERA (Overlap, Precision, Emotion, Repetition, and Attention) hypothesis for music-to-language transfer-unsaturation and utilization. Practically, the findings cast doubt on the application of nonperceptual based instrumental music training to enhance Cantonese ESL learners' perceptual learning of English stress. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21266478.

Ethics of care challenge to advance directives for dementia patients.

Advance directives for withholding life-saving treatment are controversial for dementia patients whose previously expressed wishes conflict with their currently expressed desires. To illustrate this ethical dilemma, McMahan conceives a hypothetical case in which an intellectually proud creative woman signs an advance directive stipulating her refusal to receive life-saving treatment if she contracts a fatal condition with dementia. However, when she develops dementia and forgets this advance directive, she contracts pneumonia and now expresses a desire to live. In response to such dilemmas, scholars like Norman Cantor have defended the moral authority of advance directives by giving credence to one's prior competent wishes over one's current incompetent preferences. I argue that their arguments, which are rooted in the principle of respect for autonomy, operate under ableist assumptions about incompetent persons and exclude other important features of respect. I propose an ethics of care model as an alternative moral approach that reconceptualises respect as a matter of caring about people's contemporaneous interests, even if they are not competently conceived. It fosters the virtues of care by encouraging healthcare providers to recognise dementia patients as legitimate narrative agents capable of authoring their own evolving life story. I argue that the ethics of care model not only provides an ethical defence of the creative woman's current incompetent desire to live despite her advance directive, but also vindicates our moral intuitions about what it means to demonstrate respect to dementia patients.

Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis.

Neural stem cells, the source of newborn neurons in the adult hippocampus, are intimately involved in learning and memory, mood, and stress response. Despite considerable progress in understanding the biology of neural stem cells and neurogenesis, regulating the neural stem cell population precisely has remained elusive because we have lacked the specific targets to stimulate their proliferation and neurogenesis. The orphan nuclear receptor TLX/NR2E1 governs neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is not well understood because its endogenous ligand is not known. Here, we identify oleic acid (18:1ω9 monounsaturated fatty acid) as such a ligand. We first show that oleic acid is critical for neural stem cell survival. Next, we demonstrate that it binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes, which in turn increases neural stem cell mitotic activity and drives hippocampal neurogenesis in mice. Interestingly, oleic acid-activated TLX strongly up-regulates cell cycle genes while only modestly up-regulating neurogenic genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation and drive the progeny toward neuronal lineage. Oleic acid thus serves as a metabolic regulator of TLX activity that can be used to selectively target neural stem cells, paving the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis.

Towards a Native OPERA Hypothesis: Musicianship and English Stress Perception.

Musical experience facilitates speech perception. French musicians, to whom stress is foreign, have been found to perceive English stress more accurately than French non-musicians. This study investigated whether this musical advantage also applies to native listeners. English musicians and non-musicians completed an English stress discrimination task and two control tasks. With age, non-verbal intelligence and short-term memory controlled, the musicians exhibited a perceptual advantage relative to the non-musicians. This perceptual advantage was equally potent to both trochaic and iambic stress patterns. In terms of perceptual strategy, the two groups showed differential use of acoustic cues for iambic but not trochaic stress. Collectively, the results could be taken to suggest that musical experience enhances stress discrimination even among native listeners. Remarkably, this musical advantage is highly consistent and does not particularly favour either stress pattern. For iambic stress, the musical advantage appears to stem from the differential use of acoustic cues by musicians. For trochaic stress, the musical advantage may be rooted in enhanced durational sensitivity.

Musicianship Influences Language Effect on Musical Pitch Perception.

Given its practical implications, the effect of musicianship on language learning has been vastly researched. Interestingly, growing evidence also suggests that language experience can facilitate music perception. However, the precise nature of this facilitation is not fully understood. To address this research gap, I investigated the interactive effect of language and musicianship on musical pitch and rhythmic perception. Cantonese and English listeners, each divided into musician and non-musician groups, completed the Musical Ear Test and the Raven's 2 Progressive Matrices. Essentially, an interactive effect of language and musicianship was found on musical pitch but not rhythmic perception. Consistent with previous studies, Cantonese language experience appeared to facilitate musical pitch perception. However, this facilitatory effect was only present among the non-musicians. Among the musicians, Cantonese language experience did not offer any perceptual advantage. The above findings reflect that musicianship influences the effect of language on musical pitch perception. Together with the previous findings, the new findings offer two theoretical implications for the OPERA hypothesis-bi-directionality and mechanisms through which language experience and musicianship interact in different domains.

Cardiovascular Toxicity of Androgen Deprivation Therapy.

PURPOSE OF REVIEW: Androgen deprivation therapy (ADT) is the standard of care for the treatment of advanced prostate cancer (PC). ADT, particularly with GnRH agonists, leads to increased risk of cardiovascular disease, including myocardial infarction, hypertension, and stroke. This review discusses the options of ADT, the mechanism of ADT-associated cardiovascular side effects, and potential benefit by using GnRH antagonists. RECENT FINDINGS: GnRH antagonists have relatively less cardiovascular adverse effects compared to GnRH agonists. We highlight on a recently published phase III clinical trial on the oral GnRH antagonist, relugolix, and its comparative benefit to traditional GnRH agonist regarding development of cardiovascular disease. Recent data reinforces that GnRH antagonists have a more favorable cardiovascular outcomes compared to GnRH agonists yet maintain a similar efficacy profile. From the data we reviewed, GnRH antagonists may be the preferred method of ADT for PC, but further data with primary cardiovascular outcomes are warranted.

Cantonese advantage on English stress perception: Constraints and neural underpinnings.

A prevailing conception of cross-linguistic transfer is that first language experience poses perceptual interference, or at best null effect, on second language speech perception. Surprisingly, a recent study found that Cantonese listeners outperformed English listeners on English stress perception. The present study further evaluated whether segmental variations would constrain the Cantonese advantage on English stress perception. Cantonese and English listeners were tested with both active and passive oddball paradigms in which ERP responses to English stress deviations were elicited. Behaviorally, the Cantonese listeners exhibited a perceptual advantage relative to the English listeners, but this advantage disappeared upon the introduction of segmental variations. Neurophysiologically, segmental variations diminished the P3b amplitudes of the Cantonese but not the English listeners. Collectively, results suggest that segmental variations constrain the Cantonese advantage on English stress perception.

XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53.

The XPO1 inhibitor selinexor was recently approved in relapsed/refractory DLBCL patients but only demonstrated modest anti-DLBCL efficacy, prompting us to investigate the prognostic effect of XPO1 in DLBCL patients and the rational combination therapies in high-risk DLBCL. High XPO1 expression (XPO1high) showed significant adverse prognostic impact in 544 studied DLBCL patients, especially in those with BCL2 overexpression. Therapeutic study in 30 DLBCL cell lines with various molecular and genetic background found robust cytotoxicity of selinexor, especially in cells with BCL2-rearranged (BCL2-R+) DLBCL or high-grade B-cell lymphoma with MYC/BCL2 double-hit (HGBCL-DH). However, expression of mutant (Mut) p53 significantly reduced the cytotoxicity of selinexor in overall cell lines and the BCL2-R and HGBCL-DH subsets, consistent with the favorable impact of XPO1high observed in Mut-p53-expressing patients. The therapeutic effect of selinexor in HGBCL-DH cells was significantly enhanced when combined with a BET inhibitor INCB057643, overcoming the drug resistance in Mut-p53-expressing cells. Collectively, these data suggest that XPO1 worsens the survival of DLBCL patients with unfavorable prognostic factors such as BCL2 overexpression and double-hit, in line with the higher efficacy of selinexor demonstrated in BCL2-R+ DLBCL and HGBCL-DH cell lines. Expression of Mut-p53 confers resistance to selinexor treatment, which can be overcome by combined INCB057643 treatment in HGBCL-DH cells. This study provides insight into the XPO1 significance and selinexor efficacy in DLBCL, important for developing combination therapy for relapsed/refractory DLBCL and HGBCL-DH.

Habits and Attitudes of Video Gaming and Information Technology Use in People with Schizophrenia: Cross-Sectional Survey.

BACKGROUND: Information technology and video gaming have potential advantages in the treatment of schizophrenia. However, information regarding the habits and attitudes related to internet use and video gaming in people with schizophrenia is limited. OBJECTIVE: The aim of this study was to explore the habits and attitudes regarding video gaming and information technology usage and their associated factors in people with schizophrenia in Hong Kong. METHODS: In this cross-sectional survey, service users with schizophrenia were recruited from 6 halfway hostels and 7 integrated centers for mental wellness in Hong Kong. A 79-item self-report questionnaire was utilized to explore the habits of internet use and video gaming in these people with schizophrenia. The attitude toward video gaming was assessed using the Gaming Attitudes, Motivations, and Experiences Scales. Of the 148 individuals in a convenience sample who were invited to participate in this study, 110 willingly participated (a response rate of 74.3%). The data were analyzed using descriptive statistics, a two-tailed independent t test, Pearson correlation, and principal analysis with 3 methods of rotation (varimax, equimax, and promax). RESULTS: Most participants (100/110, 90.9%) had access to the internet and half of them (54/110, 49.1%) used the internet daily mostly to watch videos (66/110, 60.0%) or read news or books, etc (42/110, 38.2%). One-third of the participants (36/110, 32.7%) used the internet to play web-based games, and most of them (88/110, 80.0%) had played a video game in the past year. The most favorable gaming platforms were cellular phones (43/88, 49%) followed by computers (19/88, 22%) and arcade cabinets (6/88, 7%). The most favorable game genre was action games (34/145, 23.4%). Those who had a bachelor's degree or higher scored lower in social interaction than those with a lower education level (P=.03). Those who played video games daily scored higher in the category of story than those who did not play daily (t86=2.03, P=.05). The most popular gaming category was autonomy and the least popular categories were violent catharsis and violent reward. Two motives, "social playing" and "evasive playing," were formed to describe the characteristics of playing video games. CONCLUSIONS: Our data showed a high internet utilization rate among people with schizophrenia in Hong Kong. Only a few of them used the internet to search for health-related information. Our study also exemplified the unique habits of gaming among the participants. Health care professionals could utilize video games to engage people with schizophrenia and promote coping with stress and provide social skills training to such people with schizophrenia. Identification of the gaming attitudes can contribute to the development of serious games for the schizophrenic population. Further investigation is vital for the promotion of mental health through web-based platforms.

The whole-genome landscape of Burkitt lymphoma subtypes.

Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole-genome sequencing (WGS) of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations, highlighting the importance of WGS for identifying driver events. Our data implicate coding and non-coding mutations in IGLL5, BACH2, SIN3A, and DNMT1. Epstein-Barr virus (EBV) infection was associated with higher mutation load, with type 1 EBV showing a higher mutational burden than type 2 EBV. Although sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6 and fewer genetic alterations in DNMT1, SNTB2, and CTCF. Silencing mutations in ID3 were a common feature of all 3 subtypes of BL. In vitro, mass spectrometry-based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. In vivo knockout of ID3 potentiated the effects of MYC, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.

From Cantonese Lexical Tone Awareness to Second Language English Vocabulary: Cross-Language Mediation by Segmental Phonological Awareness.

Purpose Cantonese lexical tone awareness is closely associated with 1st language Cantonese vocabulary knowledge, but its role in 2nd language English vocabulary knowledge was unclear. We addressed this issue by investigating whether and, if so, how Cantonese lexical tone awareness contributes to English expressive vocabulary knowledge in Hong Kong Cantonese-English bilingual children. Method A sample of 112 Hong Kong Cantonese-English bilingual 2nd graders were tested on Cantonese lexical tone awareness, English lexical stress sensitivity, Cantonese- English segmental phonological awareness, and both Cantonese and English expressive vocabulary knowledge. Results Structural equation modeling analyses revealed that Cantonese lexical tone awareness contributed indirectly to English expressive vocabulary knowledge through English lexical stress sensitivity and Cantonese-English segmental phonological awareness. Conclusion These results demonstrate the role of Cantonese lexical tone awareness in Cantonese-English bilingual children's English vocabulary knowledge. This also underscores the importance of 1st language suprasegmental phonological awareness in 2nd language expressive vocabulary knowledge.

Bidirectional Cross-Linguistic Association of Phonological Skills and Reading Comprehension: Evidence From Hong Kong Chinese-English Bilingual Readers.

This study examined the roles of first-language (L1) Chinese and second-language (L2) English phonological skills in English and Chinese reading comprehension, respectively, and their association with reading comprehension difficulties among Hong Kong Chinese-English bilingual children. We tested 258 second graders on nonverbal intelligence, working memory, phonological skills, word reading, and reading comprehension, in both Chinese and English. Structural equation modeling analyses revealed that Chinese phonological skills contributed to English reading comprehension both directly and indirectly, through the mediation of English phonological skills and English word reading. In contrast, English phonological skills contributed only indirectly to Chinese reading comprehension through L1 Chinese phonological and word reading skills. Furthermore, poor Chinese readers, poor English readers, and poor readers in both Chinese and English exhibited lower levels of lexical tone awareness than average readers, even after controlling for nonverbal intelligence, word reading, and working memory. Poor Chinese readers outperformed poor English readers and poor readers in both Chinese and English on Chinese segmental phonological awareness, and their performance was comparable to average readers. These findings suggest that both suprasegmental and segmental phonological skills are critical to the development of reading comprehension across L1 Chinese and L2 English in Hong Kong Chinese-English bilingual children.