Inflation dynamics with labour market matching : assessing alternative specifications

This paper reviews recent approaches to modeling the labour market, and assesses their implications for inflation dynamics through both their effect on marginal cost and on price-setting behavior. In a search and matching environment, we consider the following modeling setups: right-to-manage bargaining vs. efficient bargaining, wage stickiness in new and existing matches, interactions at the firm level between price and wage-setting, alternative forms of hiring frictions, search on-the-job and endogenous job separation. We find that most specifications imply too little real rigidity and, so, too volatile inflation. Models with wage stickiness and right-to-manage bargaining or with firm-specific labour emerge as the most promising candidatesInflation Dynamics, Labour Market, Business Cycle, Real Rigidities

Inflation dynamics with labour market matching: assessing alternative specifcations

This paper reviews recent approaches to modeling the labour market and assesses their implications for inflation dynamics through both their effect on marginal cost and on price-setting behavior. In a search and matching environment, we consider the following modeling setups: right-to-manage bargaining vs. efficient bargaining, wage stickiness in new and existing matches, interactions at the firm level between price and wage-setting, alternative forms of hiring frictions, search on-the-job and endogenous job separation. We find that most specifications imply too little real rigidity and, so, too volatile inflation. Models with wage stickiness and right-to-manage bargaining or with firm-specific labour emerge as the most promising candidates.Inflation Dynamics, Labour Market, Business Cycle, Real Rigidities

Inflation dynamics with labour market matching: assessing alternative specifications

This paper reviews recent approaches to modeling the labour market and assesses their implications for inflation dynamics through both their effect on marginal cost and on price-setting behaviour. In a search and matching environment, we consider the following modeling setups: right-to-manage bargaining vs. efficient bargaining, wage stickiness in new and existing matches, interactions at the firm level between price and wage-setting, alternative forms of hiring frictions, search on-the-job and endogenous job separation. We find that most specifications imply too little real rigidity and, so, too volatile inflation. Models with wage stickiness and right-to-manage bargaining or with firm-specific labour emerge as the most promising candidates. JEL Classification: E31, E32, E24, J64business cycle, Inflation Dynamics, labour market, real rigidities

Inflation dynamics with labour market matching: assessing alternative specifications

This paper reviews recent approaches to modeling the labour market and assesses their implications for inflation dynamics through both their effect on marginal cost and on price-setting behavior. In a search and matching environment, we consider the following modeling setups: right-to-manage bargaining vs. efficient bargaining, wage stickiness in new and existing matches, interactions at the firm level between price and wage-setting, alternative forms of hiring frictions, search on-the-job and endogenous job separation. We find that most specifications imply too little real rigidity and, so, too volatile inflation. Models with wage stickiness and right-to-manage bargaining or with firm-specific labour emerge as the most promising candidates.Labor market ; Business cycles

Chromosomal microarray analysis-a routine clinical genetic test for patients with schizophrenia.

Aetiological diagnosis for patients with schizophrenia was long thought to be impossible. However, genomic abnormalities with clear causal relevance can now be identified in a consistent minority of cases using chromosomal microarray analysis (CMA; also known as array Comparative Genomic Hybridization or array-CGH). Analogous to a karyotype but with dramatically improved genome-wide resolution, CMA can inform diagnosis and clinical management by identifying sub-microscopic segments of missing (deleted) or additional (duplicated) chromosomal material known as copy number variants (CNVs). CMA is sensitive, reliable, and widely available in clinical laboratories around the world, including major medical centres in the developing world. Costs are competitive with other investigations such as neuroimaging. CMA is now a standard first-line diagnostic test for intellectual disability and autism where 10-20% of affected individuals have a clinically-relevant deletion or duplication (1). Widespread application of CMA testing in these populations has increased confidence in diagnostic interpretation, enhanced the prognostic evidence base, and facilitated research progress (2). In our view, the time has come to translate replicated research findings with proven clinical utility into routine diagnostic practice for patients with schizophrenia

Multicenter Consensus Approach to Evaluation of Neonatal Hypotonia in the Genomic Era: A Review

IMPORTANCE: Infants with hypotonia can present with a variety of potentially severe clinical signs and symptoms and often require invasive testing and multiple procedures. The wide range of clinical presentations and potential etiologies leaves diagnosis and prognosis uncertain, underscoring the need for rapid elucidation of the underlying genetic cause of disease. OBSERVATIONS: The clinical application of exome sequencing or genome sequencing has dramatically improved the timely yield of diagnostic testing for neonatal hypotonia, with diagnostic rates of greater than 50% in academic neonatal intensive care units (NICUs) across Australia, Canada, the UK, and the US, which compose the International Precision Child Health Partnership (IPCHiP). A total of 74% (17 of 23) of patients had a change in clinical care in response to genetic diagnosis, including 2 patients who received targeted therapy. This narrative review discusses the common causes of neonatal hypotonia, the relative benefits and limitations of available testing modalities used in NICUs, and hypotonia management recommendations. CONCLUSIONS AND RELEVANCE: This narrative review summarizes the causes of neonatal hypotonia and the benefits of prompt genetic diagnosis, including improved prognostication and identification of targeted treatments which can improve the short-term and long-term outcomes. Institutional resources can vary among different NICUs; as a result, consideration should be given to rule out a small number of relatively unique conditions for which rapid targeted genetic testing is available. Nevertheless, the consensus recommendation is to use rapid genome or exome sequencing as a first-line testing option for NICU patients with unexplained hypotonia. As part of the IPCHiP, this diagnostic experience will be collected in a central database with the goal of advancing knowledge of neonatal hypotonia and improving evidence-based practice

Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model

Background Genotype-first and within-family studies can elucidate factors that contribute to psychiatric illness. Combining these approaches, we investigated the patterns of influence of parental scores, a high-impact variant, and schizophrenia on dimensional neurobehavioral phenotypes implicated in major psychiatric disorders. Methods We quantitatively assessed cognitive (FSIQ, VIQ, PIQ), social, and motor functioning in 82 adult individuals with a de novo 22q11.2 deletion (22 with schizophrenia), and 148 of their unaffected parents. We calculated within-family correlations and effect sizes of the 22q11.2 deletion and schizophrenia, and used linear regressions to assess contributions to neurobehavioral measures. Results Proband-parent intra-class correlations (ICC) were significant for cognitive measures (e.g. FSIQ ICC = 0.549, p < 0.0001), but not for social or motor measures. Compared to biparental scores, the 22q11.2 deletion conferred significant impairments for all phenotypes assessed (effect sizes -1.39 to -2.07 s.d.), strongest for PIQ. There were further decrements in those with schizophrenia. Regression models explained up to 37.7% of the variance in IQ and indicated that for proband IQ, parental IQ had larger effects than schizophrenia. Conclusions This study, for the first time, disentangles the impact of a high-impact variant from the modifying effects of parental scores and schizophrenia on relevant neurobehavioral phenotypes. The robust proband-parent correlations for cognitive measures, independent of the impact of the 22q11.2 deletion and of schizophrenia, suggest that, for certain phenotypes, shared genetic variation plays a significant role in expression. Molecular genetic and predictor studies are needed to elucidate shared factors and their contribution to psychiatric illness in this and other high-risk groups

Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor

Multiple TREX mRNA export complex subunits (e.g., THOC1, THOC2, THOC5, THOC6, THOC7) have now been implicated in neurodevelopmental disorders (NDDs), neurodegeneration and cancer. We previously implicated missense and splicing-defective THOC2 variants in NDDs and a broad range of other clinical features. Here we report 10 individuals from nine families with rare missense THOC2 variants including the first case of a recurrent variant (p.Arg77Cys), and an additional individual with an intragenic THOC2 microdeletion (Del-Ex37-38). Ex vivo missense variant testing and patient-derived cell line data from current and published studies show 9 of the 14 missense THOC2 variants result in

Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study

BACKGROUND: Most neonatal and infantile-onset epilepsies have presumed genetic aetiologies, and early genetic diagnoses have the potential to inform clinical management and improve outcomes. We therefore aimed to determine the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in this population. METHODS: We conducted an international, multicentre, cohort study (Gene-STEPS), which is a pilot study of the International Precision Child Health Partnership (IPCHiP). IPCHiP is a consortium of four paediatric centres with tertiary-level subspecialty services in Australia, Canada, the UK, and the USA. We recruited infants with new-onset epilepsy or complex febrile seizures from IPCHiP centres, who were younger than 12 months at seizure onset. We excluded infants with simple febrile seizures, acute provoked seizures, known acquired cause, or known genetic cause. Blood samples were collected from probands and available biological parents. Clinical data were collected from medical records, treating clinicians, and parents. Trio genome sequencing was done when both parents were available, and duo or singleton genome sequencing was done when one or neither parent was available. Site-specific protocols were used for DNA extraction and library preparation. Rapid genome sequencing and analysis was done at clinically accredited laboratories, and results were returned to families. We analysed summary statistics for cohort demographic and clinical characteristics and the timing, diagnostic yield, and clinical impact of rapid genome sequencing. FINDINGS: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 100 infants with new-onset epilepsy, of whom 41 (41%) were girls and 59 (59%) were boys. Median age of seizure onset was 128 days (IQR 46-192). For 43 (43% [binomial distribution 95% CI 33-53]) of 100 infants, we identified genetic diagnoses, with a median time from seizure onset to rapid genome sequencing result of 37 days (IQR 25-59). Genetic diagnosis was associated with neonatal seizure onset versus infantile seizure onset (14 [74%] of 19 vs 29 [36%] of 81; p=0·0027), referral setting (12 [71%] of 17 for intensive care, 19 [44%] of 43 non-intensive care inpatient, and 12 [28%] of 40 outpatient; p=0·0178), and epilepsy syndrome (13 [87%] of 15 for self-limited epilepsies, 18 [35%] of 51 for developmental and epileptic encephalopathies, 12 [35%] of 34 for other syndromes; p=0·001). Rapid genome sequencing revealed genetic heterogeneity, with 34 unique genes or genomic regions implicated. Genetic diagnoses had immediate clinical utility, informing treatment (24 [56%] of 43), additional evaluation (28 [65%]), prognosis (37 [86%]), and recurrence risk counselling (all cases). INTERPRETATION: Our findings support the feasibility of implementation of rapid genome sequencing in the clinical care of infants with new-onset epilepsy. Longitudinal follow-up is needed to further assess the role of rapid genetic diagnosis in improving clinical, quality-of-life, and economic outcomes. FUNDING: American Academy of Pediatrics, Boston Children's Hospital Children's Rare Disease Cohorts Initiative, Canadian Institutes of Health Research, Epilepsy Canada, Feiga Bresver Academic Foundation, Great Ormond Street Hospital Charity, Medical Research Council, Murdoch Children's Research Institute, National Institute of Child Health and Human Development, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, One8 Foundation, Ontario Brain Institute, Robinson Family Initiative for Transformational Research, The Royal Children's Hospital Foundation, University of Toronto McLaughlin Centre