Genetic aetiologies for childhood speech disorder: Novel pathways co-expressed during brain development

Childhood apraxia of speech (CAS), the prototypic severe childhood speech disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in a third of cases, implicating around 20 single genes to date. Here we aimed to identify molecular causation in 70 unrelated probands ascertained with CAS. We performed trio genome sequencing. Our bioinformatic analysis examined single nucleotide, indel, copy number, structural and short tandem repeat variants. We prioritised appropriate variants arising de novo or inherited that were expected to be damaging based on in silico predictions. We identified high confidence variants in 18/70 (26%) probands, almost doubling the current number of candidate genes for CAS. Three of the 18 variants affected SETBP1, SETD1A and DDX3X, thus confirming their roles in CAS, while the remaining 15 occurred in genes not previously associated with this disorder. Fifteen variants arose de novo and three were inherited. We provide further novel insights into the biology of child speech disorder, highlighting the roles of chromatin organization and gene regulation in CAS, and confirm that genes involved in CAS are co-expressed during brain development. Our findings confirm a diagnostic yield comparable to, or even higher, than other neurodevelopmental disorders with substantial de novo variant burden. Data also support the increasingly recognised overlaps between genes conferring risk for a range of neurodevelopmental disorders. Understanding the aetiological basis of CAS is critical to end the diagnostic odyssey and ensure affected individuals are poised for precision medicine trials

Fixing it for PFA Scotland: building union influence out of a transnational project to tackle match-fixing in football

This article deploys frameworks from the fields of trade union theory and professional football governance theory to gain an understanding of the tactics deployed by the Professional Footballers’ Association, Scotland (PFAS) for collectively representing the interests of its members. The article explores how the union used the advantages gained through participation in a counter match-fixing project managed by FIFPro to establish itself as a member of an array of committees, task groups and panels so that it might become the collective ‘voice’ of players at the institutional level in football. The article commences with a review of the industrial relations landscape of professional football and the ‘peculiarities’ of the labour market that have produced equally unique trade union strategies that seek to individualise rather than collectivise wage bargaining. The implications of such a strategy are felt in the lack of appropriate contemporary theories of trade union power that might act as explanatory frameworks to aid an understanding of the tactics deployed by PFAS. The article proposes a return to a political institutional model of trade union power popularised by Sidney and Beatrice Webb in the late nineteenth-century. An analysis of interview data collected from a small cohort of expert informants shows that PFAS has taken advantage of a new body in Scottish professional football, the integrity forum, to establish itself as a credible and trustworthy voice of players within broader governing structures, while acknowledging that its sphere of influence remains constrained within a system dominated by more established institutions

Probability of Major Depression Classification Based on the SCID, CIDI and MINI Diagnostic Interviews : A Synthesis of Three Individual Participant Data Meta-Analyses

Three previous individual participant data meta-analyses (IPDMAs) reported that, compared to the Structured Clinical Interview for the DSM (SCID), alternative reference standards, primarily the Composite International Diagnostic Interview (CIDI) and the Mini International Neuropsychiatric Interview (MINI), tended to misclassify major depression status, when controlling for depression symptom severity. However, there was an important lack of precision in the results.To compare the odds of the major depression classification based on the SCID, CIDI, and MINI.We included and standardized data from 3 IPDMA databases. For each IPDMA, separately, we fitted binomial generalized linear mixed models to compare the adjusted odds ratios (aORs) of major depression classification, controlling for symptom severity and characteristics of participants, and the interaction between interview and symptom severity. Next, we synthesized results using a DerSimonian-Laird random-effects meta-analysis.In total, 69,405 participants (7,574 [11%] with major depression) from 212 studies were included. Controlling for symptom severity and participant characteristics, the MINI (74 studies; 25,749 participants) classified major depression more often than the SCID (108 studies; 21,953 participants; aOR 1.46; 95% confidence interval [CI] 1.11-1.92]). Classification odds for the CIDI (30 studies; 21,703 participants) and the SCID did not differ overall (aOR 1.19; 95% CI 0.79-1.75); however, as screening scores increased, the aOR increased less for the CIDI than the SCID (interaction aOR 0.64; 95% CI 0.52-0.80).Compared to the SCID, the MINI classified major depression more often. The odds of the depression classification with the CIDI increased less as symptom levels increased. Interpretation of research that uses diagnostic interviews to classify depression should consider the interview characteristics

Not a Super Decision: The 1986 Wage Case

This paper examines the June 1986 National Wage Case decision of the Australian Conciliation and Arbitration Commission. After providing information on the context in which the case occurred, in particular, Australia’s worsening economic situation in 1985 and 1986, the paper proceeds to examine the Commission’s decision with respect to the adjustment for changes in the Consumer Price Index, the productivity/superannuation claim, and a new set of wage determination principles. The paper argues that the Commission’s handling of the productivity/superannuation claim is confused and inconsistent, which can be explained in terms of a disagreement amongst those who sat on the case on how to respond to the claim in the context of a worsening economy.