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Background and Purpose:Consistent measurement of respectful maternity care (RMC) is lacking. This Delphi study assessed consensus about indicators of RMC.Methods:A multidisciplinary panel assessed items (n= 201) drawn from global literature. Over two rounds, the panel rated importance, relevance, and clarity, and ranked priority within 17 domains including communication, autonomy, support, stigma, discrimination, and mistreatment. Qualitative feedback supported the analysis.Results:In Round One, 191 indicators exceeded a content validation index of 0.80. In Round Two, Kendall’sWranged from 0.081 (p= .209) to 0.425 (p< .001) across domains. Fourteen indicators received strong support. Changes in indicator assessment between rounds prevented agreement stability assessment.Conclusion:The indicators comprise a registry of items for use in perinatal care research.

Importance: Concussions are common among children and youth. To date, the pediatric concussion literature has focused on quantitative reports of the effects of concussion and return-to-activity guidelines. However, the subjective experiences of children and youth returning to occupations postconcussion have largely been ignored. An understanding of these experiences is critical to inform effective concussion management. Objective: To investigate the experiences of children and youth returning to occupations after sustaining a concussion and the impacts on their future engagement in occupation. Design: Qualitative interpretive description was used for data analysis and interpretation. Setting: Community. Participants: Children and youth ages 11 to 18 yr from a cohort study were recruited to be interviewed about their experiences of engaging in occupations postconcussion. Outcomes and Measures: Interviews were conducted 3 to 24 mo postconcussion, transcribed verbatim, and analyzed using interpretive description to identify themes. Results: Eight children and youth (5 male, 3 female) were included. Analyses revealed three themes of the experiences of children and youth returning to occupations after concussion: diverse experiences of concussion, knowledge is key to concussion management, and concussions affect occupational engagement. Conclusions and Relevance: This study highlights the importance of considering a person’s needs to enable effective concussion treatment plans. The results suggest the need for an occupation-based framework to guide interventions in pediatric concussion management. What This Article Adds: Our findings indicate that children and youth report variable recovery patterns, a lack of knowledge about concussion recovery, and a negative effect of concussion on occupational engagement.

Heterozygous KMT2B variants are a common cause of dystonia. A novel synonymous KMT2B variant, c.5073CT (p.Gly1691=) was identified in an individual with childhood-onset progressive dystonia.The splicing impact of c.5073CT was assessed using an in vitro exon-trapping assay. The genomic region of KMT2B exons 23-26 was cloned into the pSpliceExpress plasmid between exon 2 and 3 of the rat Ins2 gene. The c.5073CT variant was then introduced through site-directed mutagenesis. The KMT2B wild-type and c.5073CT plasmids were transfected separately into HeLa cells and RNA was extracted 48 hours after transfection. The RNA was reverse transcribed to produce cDNA, which was PCR amplified using primers annealing to the flanking rat Ins2 sequences.Sanger sequencing of the PCR products revealed that c.5073CT caused a novel splice donor site and therefore a 5-bp deletion of KMT2B exon 23 in mature mRNA, leading to a coding frameshift and premature stop codon (p.Lys1692AsnfsTer7).To our knowledge, this is the first report of a KMT2B synonymous variant associated with dystonia. Reassessment of synonymous variants may increase diagnostic yield for inherited disorders including monogenic dystonia. This is of clinical importance, given the generally favourable response to deep brain stimulation for KMT2B-related dystonia.

usc Refereed/Peer-reviewed Purpose: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy). Methods: A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases. Results: Informative RNA assay data were obtained for 96% of cases, enabling variant reclassification for 75% variants that can be used for genetic counseling (71%), to inform clinical care (32%) and prenatal counseling (41%). Variant-associated mis-splicing was highly reproducible for 28 cases with samples from ≥2 affected individuals or heterozygotes and 10 cases with ≥2 biospecimens. PCR amplicons encompassing another segregated heterozygous variant was vital for clinical interpretation of 22 of 79 variants to phase RNA splicing events and discern complete from partial mis-splicing. Conclusion: RNA diagnostics enabled provision of a genetic diagnosis for 64% of recruited cases. PCR-based RNA diagnostics has capacity to analyze 81.3% of clinically significant genes, with long amplicons providing an advantage over RNA sequencing to phase RNA splicing events. The Australasian Consortium for RNA Diagnostics (SpliceACORD) provide clinically-endorsed, standardized protocols and recommendations for interpreting RNA assay data.

Aims Pharmaco-invasive percutaneous coronary intervention (PI-PCI) is recommended for patients with ST-elevation myocardial infarction (STEMI)who are unable to undergo timely primary PCI (pPCI). The present study examined late outcomes after PI-PCI (successful reperfusion followed by scheduled PCI or failed reperfusion and rescue PCI)compared with timely and late pPCI (>120 min from first medical contact). Methods and results All patients with STEMI presenting within 12 h of symptom onset, who underwent PCI during their initial hospitalization at Liverpool Hospital (Sydney), from October 2003 to March 2014, were included. Amongst 2091 STEMI patients (80% male), 1077 (52%)underwent pPCI (68% timely, 32% late), and 1014 (48%)received PI-PCI (33% rescue, 67% scheduled). Mortality at 3 years was 11.1% after pPCI (6.7% timely, 20.2% late) and 6.2% after PI-PCI (9.4% rescue, 4.8% scheduled); P < 0.01. After propensity matching, the adjusted mortality hazard ratio (HR) for timely pPCI compared with scheduled PCI was 0.9 (95% CIs 0.4–2.0) and compared with rescue PCI was 0.5 (95% CIs 0.2–0.9). The adjusted mortality HR for late pPCI, compared with scheduled PCI was 2.2 (95% CIs 1.2–3.1)and compared with rescue PCI, it was 1.5 (95% CIs 0.7–2.0). Conclusion Patients who underwent late pPCI had higher mortality rates than those undergoing a pharmaco-invasive strategy. Despite rescue PCI being required in a third of patients, a pharmaco-invasive approach should be considered when delays to PCI are anticipated, as it achieves better outcomes than late pPCI.

Objectives To retrospectively review attendance and outcomes of a single centre, integrated multi-disciplinary (MDT) neurogenomics clinic at St Vincent’s Hospital, Sydney. Methods An audit of patients who attended the neurogenomics clinic was conducted over a 28-month period from 2017 to 2020. The clinic comprises of neurologists, clinical geneticists and genetic counsellors assessing each of the patients concurrently during the consultation. Results In the audit period 99 patients were referred spanning 45 different clinical diagnoses. Following MDT assessment, 23% (23/99) of referring diagnoses were revised. Seventy-nine patients (80%) underwent genetic testing. The type of genetic tests ordered includes 41 exome-based panels, 14 whole genome sequencing, 13 single gene tests, 30 repeat expansion disorders and 2 chromosomal microarrays. Molecular confirmation was achieved in 22 patients following testing a yield of 28% (22/79); of which, 2% had their clinical diagnosis revised following testing. Overall, a diagnosis was achieved in 29/99 patients (29%), of whom 7 patients‘ diagnosis was achieved without genetic testing. From referral to the results of genetic testing, 25% (25/99) of patients had their diagnosis revised as a result of MDT input. Conclusions Provision of an integrated multidisciplinary neurogenomics clinic in a tertiary setting provides an invaluable service with a diagnostic yield of 28%. This model provides a gold standard for diagnostic evaluation of patients with suspected neurogenetic disorders. Psychosocial benefits for patients, such as convenience/satisfaction of an MDT clinic, psychological closure for patients/families, and reproductive options enabled by achieving a genetic diagnosis, will be audited via patient survey.

Positive sense single-stranded RNA viruses undergo three mutually exclusive processes to replicate within a cell. These are translation to produce proteins, replication to produce RNA viral genomes, and packaging to form virions. The allocation of newly synthesised viral genomes to these processes, which can be regarded as life-history traits, may be subject to natural selection for efficient reproduction. Here, we develop a mathematical model of the process of intracellular viral replication to study alternative strategies for the allocation and reallocation of viral genomes to these processes. We explore four cases of the model: (1) Free Movement, in which viral genomes can freely be allocated and reallocated among translation, replication and packaging; (2) Unidirectional Reallocation, in which allocation occurs freely but reallocation can only proceed from translation to replication to packaging; (3) Conveyor Belt, in which viral genomes are first allocated to translation, then passed on to replication and finally to packaging; and (4) Permanent Allocation in which new genomes are allocated to the three processes but not reallocated between them. We apply this model to hepatitis C virus and study changes in the production of virus as the rates of allocation and reallocation are varied. We find that high viral production occurs when allocation and reallocation of the genome are weighted towards the translation and replication processes. The replication process in particular is favoured. The most productive strategy is a form of the Free Movement model in which genomes are allocated entirely to the replication-translation cycle while allowing some genomes to be packaged through reallocation.

The present UK criterion standard for assessing children with suspected inflammatory bowel disease (IBD) is upper endoscopy, ileocolonoscopy, and barium follow-through (BaFT). Significant doses of radiation, unpalatable contrast, and volume intolerance are involved with BaFT. Practice in investigating Crohn disease (CD) is changing with the increasing use of magnetic resonance imaging (MRI). The aim of the present study was to compare BaFT and a new abdominal MRI protocol in a paediatric IBD population.All consecutive patients with a new diagnosis of IBD or requiring reassessment from September 2008 to December 2010 were investigated with both abdominal MRI and BaFT in accordance with a specific local paediatric IBD protocol. The studies were reported by nonblinded radiologists with an interest in gastrointestinal imaging. The reports were compared in conjunction with case note review.Eighty-seven patients underwent both BaFT and MRI abdomen. Thirty-one percent of patients had additional pathology on MRI, not seen on the BaFT. Sixty-seven percent of patients (n=59) had an MRI finding equivalent to BaFT. Using histology as a criterion standard for detecting terminal ileal disease, BaFT had a sensitivity and specificity of 76% and 67%, and MRI had a sensitivity and specificity of 83% and 95%, respectively.This is the largest series of small bowel MRI in a paediatric population. MRI reports were at least equivalent to BaFT. MRI had higher sensitivity and, particularly, specificity in detecting terminal ileal pathology. These findings suggest that MRI should become the criterion standard investigation in children with IBD in centres with appropriate expertise, with zero radiation exposure being highly advantageous.

It has previously been demonstrated, using an ultracytochemical technique, that the photoreceptive microvilli of crab retinae contain a magnesium-dependent phosphatase that hydrolyses the artificial substrate 4-nitrophenylphosphate. Whilst many phosphatases hydrolyse 4-nitrophenylphosphate, the properties of the microvillar enzyme indicated that it is not a conventional acid or alkaline phosphatase. Using the same technique, it is now shown that a similar activity resides in the rhabdomeric microvilli of both the lateral compound eye and the ventral photoreceptors of Limulus polyphemus as well as in the compound eyes of the freshwater crayfish Cherax destructor and the fly Lucilia cuprina. Control cytochemical procedures performed on crayfish and fly showed that in these species too the activity is magnesium-dependent and is not due to a Na+/K+ ATPase.