Summary
An ageing population and rising healthcare costs are challenging cost‐efficient hospital systems wanting to adapt, employing novel organisational structures designed to merge diverse skill ...sets. This needs not only physician and nursing leadership but also new models of care. Anaesthetists have expanded their role into the broader multidisciplinary field of peri‐operative medicine, emphasising collaboration and safety in health teams. A greater focus on patient‐centred care and shared decision making, along with validated metrics to quantify quality improvement activities, have emphasised the importance of comfort, patient satisfaction and quality of life after surgery. Shared decision‐making is more likely to be manifest in a flat hierarchy in which each member of the team brings their own experience and skills to optimise patient care. Successful surgery is best achieved by a coordinated, multidisciplinary team, embedded in a culture of collaboration and safety.
Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits—specifically reading disability (RD) and ...language impairment (LI)—are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co‐occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome‐wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10−7) and COL4A2 (OR = 1.71, P = 7.59 × 10−7). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10−7). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.
ZNF385D associates with comorbid reading disability and language impairment, as well as overall fiber tract and brain volumes.
Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships ...between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age. Income was logarithmically associated with brain surface area. Among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data imply that income relates most strongly to brain structure among the most disadvantaged children.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Reading disability (RD) and language impairment (LI) are common learning disabilities that make acquisition and utilization of reading and verbal language skills, respectively, difficult for affected ...individuals. Both disorders have a substantial genetic component with complex inheritance. Despite decades of study, reading and language, like many other complex traits, consistently evade identification of causative and functional variants. We previously identified a putative functional risk variant, named BV677278 for its GenBank accession number, for RD in DCDC2. This variant consists of an intronic microdeletion and a highly polymorphic short tandem repeat (STR) within its breakpoints. We have also shown this STR to bind to an unknown nuclear protein with high specificity. Here, we replicate BV677278’s association with RD, expand its association to LI, identify the BV677278-binding protein as the transcription factor ETV6, and provide compelling genetic evidence that BV677278 is a regulatory element that influences reading and language skills. We also provide evidence that BV677278 interacts nonadditively with KIAA0319, an RD-associated gene, to adversely affect several reading and cognitive phenotypes. On the basis of these data, we propose a new name for BV677278: “READ1” or “regulatory element associated with dyslexia 1.”
There have been many conflicting reports concerning the association of the DRD2 locus with alcohol dependence (AD). To investigate whether these findings could be reconciled by considering the ...genomic region of DRD2 in greater detail, we conducted two separate association studies of AD in 1220 European-American subjects using family-based (488 subjects) and case–control (318 cases and 414 controls) designs, and 43 single nucleotide polymorphisms mapped to the gene cluster of NCAM1, TTC12, ANKK1 and DRD2. We used a generalized linear model and haplotype score tests for the case–control sample, and the family-based association test for the family sample. Haplotype associations centered on TTC12 exon 3 rs1893699–rs723077; optimal individual haplotype simulated P-value (Poihs) = 0.00021 in both independent samples (family and case–control). Additional AD-associated haplotypes centered around NCAM1 exon 12 in the family sample (Poihs = 0.0032), and at exons 2 and 5 of ANKK1 in the case–control sample (Poihs = 0.00058). LD contrasts between cases and controls support selection at TTC12 exon 3 and ANKK1 exon 2. The armadillo repeat domains encoded by TTC12 and dopamine interact in the Wnt pathway and may have effects on dopamine cell development in the ventral midbrain. We conclude that risk for AD is attributable in part to variants in four regions within this cluster: exon 3 of TTC12, exon 12/intron13 of NCAM1 and exons 2 and 5 of ANKK1. The complexity of these relationships, many of which replicate between our independent samples, may explain prior inconsistent results.
DYX2 on 6p22 is the most replicated reading disability (RD) locus. By saturating a previously identified peak of association with single nucleotide polymorphism markers, we identified a large ...polymorphic deletion that encodes tandem repeats of putative brain-related transcription factor binding sites in intron 2 of DCDC2. Alleles of this compound repeat are in significant disequilibrium with multiple reading traits. RT-PCR data show that DCDC2 localizes to the regions of the brain where fluent reading occurs, and RNA interference studies show that down-regulation alters neuronal migration. The statistical and functional studies are complementary and are consistent with the latest clinical imaging data for RD. Thus, we propose that DCDC2 is a candidate gene for RD.
The goals were to isolate and to estimate the genetic susceptibility to retinopathy of prematurity.
A retrospective study (1994-2004) from 3 centers was performed with zygosity data for premature ...twins who were born at a gestational age of < or = 32 weeks and survived beyond a postmenstrual age of 36 weeks. Retinopathy of prematurity was diagnosed and staged by pediatric ophthalmologists at each center. Data analyses were performed with mixed-effects logistic regression analysis and latent variable probit modeling.
A total of 63 monozygotic and 137 dizygotic twin pairs were identified and analyzed. Data on gestational age, birth weight, gender, respiratory distress syndrome, retinopathy of prematurity, bronchopulmonary dysplasia, duration of ventilation and supplemental oxygen use, and length of stay were comparable between monozygotic and dizygotic twins. In the mixed-effects logistic regression analysis for retinopathy of prematurity, gestational age and duration of supplemental oxygen use were significant covariates. After controlling for known and unknown nongenetic factors, genetic factors accounted for 70.1% of the variance in liability for retinopathy of prematurity.
In addition to prematurity and environmental factors, there is a strong genetic predisposition to retinopathy of prematurity.
Developmental dyslexia is a heritable condition, with genetic factors accounting for 44-75% of the variance in performance tests of reading component subphenotypes. Compelling genetic linkage and ...association evidence supports a quantitative trait locus in the 6p21.3 region that encodes a gene called DCDC2. In this study, we explored the contribution of two DCDC2 markers to dyslexia, related reading and memory phenotypes in nuclear families of Italian origin.
The 303 nuclear families recruited on the basis of having a proband with developmental dyslexia have been studied with 6p21.3 markers, BV677278 and rs793862. Marker-trait association was investigated by the quantitative transmission disequilibrium test (version 2.5.1) that allows for the analyses of quantitative traits. Seven phenotypes were used in association analyses, that is, word and nonword reading, word and nonword spelling, orthographic choice, memory, and the affected status based on inclusion criteria.
Quantitative transmission disequilibrium test analyses yielded evidence for association between reading skills and the BV677278 deletion (empirical P-values=0.025-0.029) and between memory and BV677278 allele 10 (empirical P-value=0.0001).
Our result adds further evidence in support of DCDC2 contributing to the deficits in developmental dyslexia. More specifically, our data support the view that DCDC2 influences both reading and memory impairments thus shedding further light into the etiologic basis and the phenotypic complexity of developmental dyslexia.
•This was a prospective before-and-after study in four major trauma centres in India over more than one year.•Data was collected at 68 Trauma Quality Improvement Meetings and the intervention was a ...Trauma Quality Improvement Meeting Checklist.•The introduction of the Trauma Quality Improvement Meeting Checklist led to more structured Meetings.•For cases brought to the Meetings, there was an increase in the discussion and agreement on preventability of death and plans for loop closure.•A Trauma Quality Improvement Meeting Checklist should be considered for all centres managing trauma patients.
Each year approximately five million people die from injuries. In countries where systems of trauma care have been introduced, death and disability have decreased. A major component of developed trauma systems is a trauma quality improvement (TQI) program and trauma quality improvement meeting (TQIM). Effective TQIMs improve trauma care by identifying and fixing problems. But globally, TQIMs are absent or unstructured in most hospitals providing trauma care. The aim of this study was to implement and evaluate a checklist for a structured TQIM.
This project was conducted as a prospective before-and-after study in four major trauma centres in India. The intervention was the introduction of a structured TQIM using a checklist, introduced with a workshop. This workshop was based on the World Health Organization (WHO) TQI Programs short course and resources, plus the developed TQIM checklist. Pre- and post-intervention data collection occurred at all meetings in which cases of trauma death were discussed. The primary outcome was TQIM Checklist compliance, defined by the discussion of, and agreement upon each of the following: preventability of death, identification of opportunities to improve care and corrective actions and a plan for closing the loop.
There were 34 meetings in each phase, with 99 cases brought to the pre-intervention phase and 125 cases brought to the post-intervention phase. There was an increase in the proportion of cases brought to the meeting for which preventability of death was discussed (from 94% to 100%, p = 0.007) and agreed (from 7 to 19%, OR 3.7; 95% CI:1.4–9.4, p = 0.004) and for which a plan for closing the loop was discussed (from 2% to 18%, OR 10.9; 95% CI:2.5–47.6, p < 0.001) and agreed (from 2% to 18%, OR 10.9; 95% CI:2.5–47.6, p < 0.001).
This study developed, implemented and evaluated a TQIM Checklist for improving TQIM processes. The introduction of a TQIM Checklist, with training, into four Indian trauma centres, led to more structured TQIMs, including increased discussion and agreement on preventability of death and plans for loop closure. A TQIM Checklist should be considered for all centres managing trauma patients.
Abstract Individuals with schizophrenia show a broad range of language impairments, including reading difficulties. A recent structural MRI (sMRI) study linked these difficulties to structural ...abnormalities in language-related regions ( Leonard et al., 2008 ). Similar regions have been implicated in primary reading disability (RD). Major hypotheses of RD implicate abnormal embryonic neuronal migration in the cortex, and genetic linkage and association studies have identified a number of candidate RD genes that are associated with neuronal migration ( Paracchini et al., 2007 ). Interestingly, evidence suggests at least some individuals with schizophrenia also show impaired neuronal migration in the cortex ( Akbarian et al., 1996 ). Thus the aim of this study was to examine the link between RD-related genes and gray matter volumes in healthy controls and schizophrenia. We used parallel independent component analysis (parallel-ICA) to examine the relationship between gray matter volumes extracted using voxel-based morphometry (VBM) and 16 single nucleotide polymorphisms (SNPs) spanning FOXP2 and four RD-related genes, DCDC2 , DYX1C1 , KIAA0319 and TTRAP . Parallel-ICA identified five sMRI–SNP relationships. Superior and inferior cerebellar networks were related to DYX1C1 and DCDC2/KIAA0319 respectively in both groups. The superior prefrontal, temporal and occipital networks were positively related to DCDC2 in the schizophrenia, but not the control group. The identified networks closely correspond to the known distribution of language processes in the cortex. Thus, reading and language difficulties in schizophrenia may be related to distributed cortical structural abnormalities associated with RD-related genes.
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