An Operatic Tradition

Adrienne Simpson's recent seminar at the Stout Centre on the Simonsen Opera Company gave striking evidence of the popularity of opera in 19th-century New Zealand, not only in cities but in the many small towns which the travelling companies included in their schedules. Today, opera is the cinderella of the arts, rebuilding in regional form after the fateful decision of the QEII to withdraw national funding from the New Zealand Opera Company and its successor, the New Zealand National Opera. In this interview, J.M. Thomson asks Adrienne Simpson why opera is such a potent force in a country where, in the view of today's policy makers, it is often considered irrelevant to cultural aspirations. In other words, how meaningful is opera to present-day New Zealand

An Operatic Tradition

Adrienne Simpson's recent seminar at the Stout Centre on the Simonsen Opera Company gave striking evidence of the popularity of opera in 19th-century New Zealand, not only in cities but in the many small towns which the travelling companies included in their schedules. Today, opera is the cinderella of the arts, rebuilding in regional form after the fateful decision of the QEII to withdraw national funding from the New Zealand Opera Company and its successor, the New Zealand National Opera. In this interview, J.M. Thomson asks Adrienne Simpson why opera is such a potent force in a country where, in the view of today's policy makers, it is often considered irrelevant to cultural aspirations. In other words, how meaningful is opera to present-day New Zealand

Tributes to Jim Collinge: Retiring Director of the Stout Research Centre

A tribute to Jim Colling

Tributes to Jim Collinge: Retiring Director of the Stout Research Centre

A tribute to Jim Colling

IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress

IRE1β is an ER stress sensor uniquely expressed in epithelial cells lining mucosal surfaces. Here, we show that intestinal epithelial cells expressing IRE1β have an attenuated unfolded protein response to ER stress. When modeled in HEK293 cells and with purified protein, IRE1β diminishes expression and inhibits signaling by the closely related stress sensor IRE1α. IRE1β can assemble with and inhibit IRE1α to suppress stress-induced XBP1 splicing, a key mediator of the unfolded protein response. In comparison to IRE1α, IRE1β has relatively weak XBP1 splicing activity, largely explained by a nonconserved amino acid in the kinase domain active site that impairs its phosphorylation and restricts oligomerization. This enables IRE1β to act as a dominant-negative suppressor of IRE1α and affect how barrier epithelial cells manage the response to stress at the host–environment interface

Definition and Characteristics of Behavioral Medicine, and Main Tasks and Goals of the International Society of Behavioral Medicine—an International Delphi Study

© 2020, The Author(s). Background: In the past decades, behavioral medicine has attained global recognition. Due to its global reach, a critical need has emerged to consider whether the original definition of behavioral medicine is still valid, comprehensive, and inclusive, and to reconsider the main tasks and goals of the International Society of Behavioral Medicine (ISBM), as the umbrella organization in the field. The purpose of the present study was to (i) update the definition and scope of behavioral medicine and its defining characteristics; and (ii) develop a proposal on ISBM’s main tasks and goals. Method: Our study used the Delphi method. A core group prepared a discussion paper. An international Delphi panel rated questions and provided comments. The panel intended to reach an a priori defined level of consensus (i.e., 70%). Results: The international panel reached consensus on an updated definition and scope of behavioral medicine as a field of research and practice that builds on collaboration among multiple disciplines. These disciplines are concerned with development and application of behavioral and biomedical evidence across the disease continuum in clinical and public health domains. Consensus was reached on a proposal for ISBM’s main tasks and goals focused on supporting communication and collaboration across disciplines and participating organizations; stimulating research, education, and practice; and supporting individuals and organizations in the field. Conclusion: The consensus on definition and scope of behavioral medicine and ISBM’s tasks and goals provides a foundational step toward achieving these goals

Undoing violent masculinity: Lynne Ramsay’s You were never really here (2018)

Reviewers described Lynne Ramsay’s You Were Never Really Here (2018) as a “Taxi Driver for a new century.” Certainly, its narrative of an inarticulate killer who is also the would-be saviour of a lost and damaged “little white girl” recalls that of Scorsese’s 1976 film., and the two films share a fragmented, hallucinatory quality. Yet what such comparisons miss is both the devastating critique of this culturally powerful narrative to be found in Ramsay’s film, and the connections it makes between this paradigmatic story of a failed and violent but ultimately sympathetic white masculinity and another: that of the traumatising mother who is responsible for the violence of her psychotic son. In this article, I explore the nature of Ramsay’s critique, arguing that her film both refuses and interrogates both of these readings of gender. Ramsay’s protagonist, like Scorsese’s, is a traumatised war veteran, but his identification is not with a fantasised and recuperative ideal masculinity but with its feminised victims: girl and mother. His tragedy is not that he fails in his rescue attempt, or that he is in thrall to the “death mother”, but that he believes that the means of this rescue might be masculinity

Credible knowledge: A pilot evaluation of a modified GRADE method using parent-implemented interventions for children with autism

Abstract Background Decision-making in child and youth mental health (CYMH) care requires recommendations that are developed through an efficient and effective method and are based on credible knowledge. Credible knowledge is informed by two sources: scientific evidence, and practice-based evidence, that reflects the "real world" experience of service providers. Current approaches to developing these recommendations in relation to CYMH will typically include evidence from one source or the other but do not have an objective method to combine the two. To this end, a modified version of the Grading Recommendations Assessment, Development and Evaluation (GRADE) approach was pilot-tested, a novel method for the CYMH field. Methods GRADE has an explicit methodology that relies on input from scientific evidence as well as a panel of experts. The panel established the quality of evidence and derived detailed recommendations regarding the organization and delivery of mental health care for children and youth or their caregivers. In this study a modified GRADE method was used to provide precise recommendations based on a specific CYMH question (i.e. What is the current credible knowledge concerning the effects of parent-implemented, early intervention with their autistic children?). Results Overall, it appeared that early, parent-implemented interventions for autism result in positive effects that outweigh any undesirable effects. However, as opposed to overall recommendations, the heterogeneity of the evidence required that recommendations be specific to particular interventions, based on the questions of whether the benefits of a particular intervention outweighs its harms. Conclusions This pilot project provided evidence that a modified GRADE method may be an effective and practical approach to making recommendations in CYMH, based on credible knowledge. Key strengths of the process included separating the assessments of the quality of the evidence and the strength of recommendations, transparency in decision-making, and the objectivity of the methods. Most importantly, this method combined the evidence and clinical experience in a more timely, explicit and simple process as compared to previous approaches. The strengths, limitations and modifications of the approach as they pertain to CYMH, are discussed

Processed pseudogenes acquired somatically during cancer development

Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5′ truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context

Homologous recombination DNA repair defects in PALB2- associated breast cancers

Abstract: Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD