Detection of trait donors and QTL boundaries for early blight resistance using local ancestry inference in a library of genomic sequences for tomato.

By conducting hierarchical clustering along a sliding window, we generated haplotypes across hundreds of re-sequenced genomes in a few hours. We leveraged our method to define cryptic introgressions underlying disease resistance in tomato (Solanum lycopersicum L.) and to discover resistant germplasm in the tomato seed bank. The genomes of 9 accessions with early blight (Alternaria linariae) disease resistance were newly sequenced and analyzed together with published sequences for 770 tomato and wild species accessions, most of which are available in germplasm collections. Identification of common ancestral haplotypes among resistant germplasm enabled rapid fine mapping of recently discovered quantitative trait loci (QTL) conferring resistance and the identification of possible causal variants. The source of the early blight QTL EB-9 was traced to a vintage tomato named 'Devon Surprise'. Another QTL, EB-5, as well as resistance to bacterial spot disease (Xanthomonas spp.), was traced to Hawaii 7998. A genomic survey of all accessions forecasted EB-9-derived resistance in several heirloom tomatoes, accessions of S. lycopersicum var. cerasiforme, and S. pimpinellifolium PI 37009. Our haplotype-based predictions were validated by screening the accessions against the causal pathogen. There was little evidence of EB-5 prevalence in surveyed contemporary germplasm, presenting an opportunity to bolster tomato disease resistance by adding this rare locus. Our work demonstrates practical insights that can be derived from the efficient processing of large genome-scale datasets, including rapid functional prediction of disease resistance QTL in diverse genetic backgrounds. Finally, our work finds more efficient ways to leverage public genetic resources for crop improvement.

Phylodynamic Insights into Global Emergence and Diversification of the Tomato Pathogen Xanthomonas hortorum pv. gardneri.

The emergence of plant pathogens is often associated with waves of unique evolutionary and epidemiological events. Xanthomonas hortorum pv. gardneri is one of the major pathogens causing bacterial spot disease of tomatoes. After its first report in the 1950s, there were no formal reports on this pathogen until the 1990s, despite active global research on the pathogens that cause tomato and pepper bacterial spot disease. Given the recently documented global distribution of X. hortorum pv. gardneri, our objective was to examine genomic diversification associated with its emergence. We sequenced the genomes of X. hortorum pv. gardneri strains collected in eight countries to examine global population structure and pathways of emergence using phylodynamic analysis. We found that strains isolated post-1990 group by region of collection and show minimal impact of recombination on genetic variation. A period of rapid geographic expansion in X. hortorum pv. gardneri is associated with acquisition of a large plasmid conferring copper tolerance by horizontal transfer and coincides with the burgeoning hybrid tomato seed industry through the 1980s. The ancestry of X. hortorum pv. gardneri is consistent with introduction to hybrid tomato seed production and dissemination during the rapid increase in trade of hybrid seeds.

De novo enhancer deletion of LMX1B produces a mild nail-patella clinical phenotype.

Critical genes involved in embryonic development are often transcription factors, regulating many downstream genes. LMX1B is a homeobox gene that is involved in formation of the limbs, eyes and kidneys, heterozygous loss-of-function sequence variants and deletions cause Nail-Patella syndrome. Most of the reported variants are localised within the gene's coding sequence, however, approximately 5%-10% of affected individuals do not have a pathogenic variant identified within this region. In this study, we present a family with four affected individuals across two generations with a deletion spanning a conserved upstream LMX1B-binding sequence. This deletion is de novo in the mother of three affected children. Furthermore, in this family, the manifestations appear limited to the nails and limbs, and therefore may reflect an attenuated phenotype of the classic Nail-Patella phenotype that includes ophthalmological and renal manifestations.

Modeling Thyroid Cancer Epidemiology in the United States Using Papillary Thyroid Carcinoma Microsimulation Model.

OBJECTIVES: Thyroid cancer incidence increased over 200% from 1992 to 2018, whereas mortality rates had not increased proportionately. The increased incidence has been attributed primarily to the detection of subclinical disease, raising important questions related to thyroid cancer control. We developed the Papillary Thyroid Carcinoma Microsimulation model (PATCAM) to answer them, including the impact of overdiagnosis on thyroid cancer incidence. METHODS: PATCAM simulates individuals from age 15 until death in birth cohorts starting from 1975 using 4 inter-related components, including natural history, detection, post-diagnosis, and other-cause mortality. PATCAM was built using high-quality data and calibrated against observed age-, sex-, and stage-specific incidence in the United States as reported by the Surveillance, Epidemiology, and End Results database. PATCAM was validated against US thyroid cancer mortality and 3 active surveillance studies, including the largest and longest running thyroid cancer active surveillance cohort in the world (from Japan) and 2 from the United States. RESULTS: PATCAM successfully replicated age- and stage-specific papillary thyroid cancers (PTC) incidence and mean tumor size at diagnosis and PTC mortality in the United States between 1975 and 2015. PATCAM accurately predicted the proportion of tumors that grew more than 3 mm and 5 mm in 5 years and 10 years, aligning with the 95% confidence intervals of the reported rates from active surveillance studies in most cases. CONCLUSIONS: PATCAM successfully reproduced observed US thyroid cancer incidence and mortality over time and was externally validated. PATCAM can be used to identify factors that influence the detection of subclinical PTCs.

Growth performance and feed utilisation of Australian hybrid abalone (Haliotis rubra × Haliotis laevigata) fed increasing dietary protein levels at three water temperatures.

Determining the macronutrient requirements for commercially valuable aquaculture species remains crucial for maximising production efficiency. Yet, such information is lacking for Australian hybrid abalone (Haliotis rubra × Haliotis laevigata), particularly with respect to life stage and water temperatures. The present study aimed to evaluate the effect of dietary protein inclusion level on the growth performance, nutrient utilisation and nutritional quality of juvenile (3·3 g) Australian hybrid abalone reared at three different temperatures representative of winter (12°C), average annual (17°C) and summer (22°C) grow-out periods and fed five diets containing graded dietary protein levels of 35, 38, 41, 44 and 47 %. Abalone growth increased with increasing water temperature with weight gains of approximately 100, 280 and 380 % of their initial weight at 12, 17 and 22°C, respectively. Furthermore, the present study clearly demonstrated that higher dietary protein inclusion levels (41 %) than those currently used commercially (35 %) would significantly improve the growth performance when water temperatures are ≥17°C without any adverse impacts on nutrient utilisation, nutrient deposition or nutritional quality of the abalone soft tissue. For example, at 22°C abalone fed a diet containing 41 % protein obtained a significantly higher weight gain percentage (421 %) compared with those fed a diet containing 35 % protein (356 %). Lastly, it is suggested that maintaining a dietary protein inclusion level of 35 % or implementing a 'least cost' feeding approach during cooler seasons, or where water temperatures are ∼12°C, may be beneficial, considering only marginal growth improvements were observed during these periods of slow growth.

Insect meal in aquafeeds: A sustainable path to enhanced mucosal immunity in fish.

The mucosal surfaces of fish, including their intestines, gills, and skin, are constantly exposed to various environmental threats, such as water quality fluctuations, pollutants, and pathogens. However, various cells and microbiota closely associated with these surfaces work in tandem to create a functional protective barrier against these conditions. Recent research has shown that incorporating specific feed ingredients into fish diets can significantly boost their mucosal and general immune response. Among the various ingredients being investigated, insect meal has emerged as one of the most promising options, owing to its high protein content and immunomodulatory properties. By positively influencing the structure and function of mucosal surfaces, insect meal (IM) has the potential to enhance the overall immune status of fish. This review provides a comprehensive overview of the potential benefits of incorporating IM into aquafeed as a feed ingredient for augmenting the mucosal immune response of fish.

The syndemic effect of COVID-19 and racial discrimination on suicide risk for Black emerging adults: Examining a model of radical healing.

Suicide is a leading cause of death among Black emerging adults. The concurrent effect of the COVID-19 pandemic and racial discrimination were projected to exacerbate suicide vulnerability for Black Americans. The purpose of the present study was to utilize a risk-resilience model to examine the effects of racial discrimination and COVID-related stress on suicide risk for Black emerging adults, as well as the moderating effect of three central components of radical healing: critical consciousness, resilience, and cultural authenticity. Study participants included 521 Black emerging adults between the ages of 18 and 29 (51.6% male; Mage = 24.6, SD = 2.6) who completed measures evaluating symptoms of racial discrimination, COVID-related stress, suicide risk, and psychological well-being. After controlling for age, gender, socioeconomic status, and general stress, structural equation modeling analyses revealed unique and interactive effects of racial discrimination, COVID-related stress, and culturally relevant protective factors on suicide risk for Black emerging adults. These findings provide preliminary insight into novel risk and protective factors that influence suicide risk for Black emerging adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinicodemographic Predictors of Tracheotomy Tube Size and Decannulation: A Multiinstitutional Retrospective Cohort Study on Tracheotomy.

OBJECTIVE: We aimed to discern clinico-demographic predictors of large (≥8) tracheostomy tube size placement, and, secondarily, to assess the effect of large tracheostomy tube size and other parameters on odds of decannulation before hospital discharge. SUMMARY OF BACKGROUND DATA: Factors determining choice of tracheostomy tube size are not well-characterized in the current literature, despite evidence linking large tracheostomy tube size with posttracheotomy tracheal stenosis. The effect of tracheostomy tube size on timing of decannulation is also unknown, an important consideration given reported associations between endotracheal tube size and probability of failed extubation. METHODS: We collected information pertaining to patients who underwent tracheotomy at 1 of 10 U.S. health care institutions between 2010 and 2019. Tracheostomy tube size was dichotomized (≥8 and <8). Multivariable logistic regression models were fit to identify predictors of (1) large tracheostomy tube size, and (2) decannulation before hospital discharge. RESULTS: The study included 5307 patients, including 2797 (52.7%) in the large tracheostomy cohort. Patient height (odds ratio [OR] = 1.060 per inch; 95% confidence interval [CI] 1.041-1.070) and obesity (1.37; 95% CI 1.1891.579) were associated with greater odds of large tracheostomy tube; otolaryngology performing the tracheotomy was associated with significantly lower odds of large tracheostomy tube (OR = 0.155; 95% CI 0.131-0.184). Large tracheostomy tube size (OR = 1.036; 95% CI 0.885-1.213) did not affect odds of decannulation. CONCLUSIONS: Obesity was linked with increased likelihood of large tracheostomy tube size, independent of patient height. Probability of decannulation before hospital discharge is influenced by multiple patient-centric factors, but not by size of tracheostomy tube.

Tissue mosaicism, FMR1 expression and intellectual functioning in males with fragile X syndrome.

Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.89-43.17 years of age). Methylation sensitive Southern blot (mSB) and Methylation Specific-Quantitative Melt Aanalysis (MS-QMA) were used to examine FMR1 methylation. FMR1 mRNA levels in blood showed strong relationships with FMR1 methylation assessed using MS-QMA in blood (n = 68; R2  = 0.597; p = 1.4 × 10-10 ) and buccal epithelial cells (BEC) (n = 62; R2  = 0.24; p = 0.003), with these measures also showing relationships with intellectual functioning scores (p < 0.01). However, these relationships were not as strong for mSB, with ~40% of males with only FM alleles that were 100% methylated and non-mosaic by mSB, showing methylation mosaicism by MS-QMA. This was confirmed through presence of detectable levels of FMR1 mRNA in blood. In summary, FMR1 methylation levels in blood and BEC examined by MS-QMA were significantly associated with FMR1 mRNA levels and intellectual functioning in males with FXS. These relationships were not as strong for mSB, which underestimated prevalence of mosaicism.

WWOX developmental and epileptic encephalopathy: Understanding the epileptology and the mortality risk.

OBJECTIVE: WWOX is an autosomal recessive cause of early infantile developmental and epileptic encephalopathy (WWOX-DEE), also known as WOREE (WWOX-related epileptic encephalopathy). We analyzed the epileptology and imaging features of WWOX-DEE, and investigated genotype-phenotype correlations, particularly with regard to survival. METHODS: We studied 13 patients from 12 families with WWOX-DEE. Information regarding seizure semiology, comorbidities, facial dysmorphisms, and disease outcome were collected. Electroencephalographic (EEG) and brain magnetic resonance imaging (MRI) data were analyzed. Pathogenic WWOX variants from our cohort and the literature were coded as either null or missense, allowing individuals to be classified into one of three genotype classes: (1) null/null, (2) null/missense, (3) missense/missense. Differences in survival outcome were estimated using the Kaplan-Meier method. RESULTS: All patients experienced multiple seizure types (median onset = 5 weeks, range = 1 day-10 months), the most frequent being focal (85%), epileptic spasms (77%), and tonic seizures (69%). Ictal EEG recordings in six of 13 patients showed tonic (n = 5), myoclonic (n = 2), epileptic spasms (n = 2), focal (n = 1), and migrating focal (n = 1) seizures. Interictal EEGs demonstrated slow background activity with multifocal discharges, predominantly over frontal or temporo-occipital regions. Eleven of 13 patients had a movement disorder, most frequently dystonia. Brain MRIs revealed severe frontotemporal, hippocampal, and optic atrophy, thin corpus callosum, and white matter signal abnormalities. Pathogenic variants were located throughout WWOX and comprised both missense and null changes including five copy number variants (four deletions, one duplication). Survival analyses showed that patients with two null variants are at higher mortality risk (p-value = .0085, log-rank test). SIGNIFICANCE: Biallelic WWOX pathogenic variants cause an early infantile developmental and epileptic encephalopathy syndrome. The most common seizure types are focal seizures and epileptic spasms. Mortality risk is associated with mutation type; patients with biallelic null WWOX pathogenic variants have significantly lower survival probability compared to those carrying at least one presumed hypomorphic missense pathogenic variant.

Lessons learnt from multifaceted diagnostic approaches to the first 150 families in Victoria's Undiagnosed Diseases Program.

BACKGROUND: Clinical exome sequencing typically achieves diagnostic yields of 30%-57.5% in individuals with monogenic rare diseases. Undiagnosed diseases programmes implement strategies to improve diagnostic outcomes for these individuals. AIM: We share the lessons learnt from the first 3 years of the Undiagnosed Diseases Program-Victoria, an Australian programme embedded within a clinical genetics service in the state of Victoria with a focus on paediatric rare diseases. METHODS: We enrolled families who remained without a diagnosis after clinical genomic (panel, exome or genome) sequencing between 2016 and 2018. We used family-based exome sequencing (family ES), family-based genome sequencing (family GS), RNA sequencing (RNA-seq) and high-resolution chromosomal microarray (CMA) with research-based analysis. RESULTS: In 150 families, we achieved a diagnosis or strong candidate in 64 (42.7%) (37 in known genes with a consistent phenotype, 3 in known genes with a novel phenotype and 24 in novel disease genes). Fifty-four diagnoses or strong candidates were made by family ES, six by family GS with RNA-seq, two by high-resolution CMA and two by data reanalysis. CONCLUSION: We share our lessons learnt from the programme. Flexible implementation of multiple strategies allowed for scalability and response to the availability of new technologies. Broad implementation of family ES with research-based analysis showed promising yields post a negative clinical singleton ES. RNA-seq offered multiple benefits in family ES-negative populations. International data sharing strategies were critical in facilitating collaborations to establish novel disease-gene associations. Finally, the integrated approach of a multiskilled, multidisciplinary team was fundamental to having diverse perspectives and strategic decision-making.

Efficacy of secondary intention healing for scalp defects-Case series from a single institution.

BACKGROUND/OBJECTIVES: As surgical techniques evolve, there remains underutilisation of secondary intention healing as a valid reconstruction option. This is largely due to concerns regarding inferiority of wound cosmesis, increased downtime with wound healing and infection risk (Dermatol Surg. 2020; 46(12): 1492-97). METHODS: We sought to look at the outcome of secondary intention healing in a cohort of patients seen at a private dermatology practice with small to medium sized scalp defects. All patients completed a satisfaction survey that further evaluated its feasibility. RESULTS: Excellent cosmetic outcome was noted with secondary intention healing for small to medium scalp defects, specifically in patients with thinning scalps that allowed healing without patchy alopecia. CONCLUSIONS: Secondary intention healing should be considered as a reconstructive option for scalp defects, especially in the right patient cohort.

Defining the 3'Epigenetic Boundary of the FMR1 Promoter and Its Loss in Individuals with Fragile X Syndrome.

This study characterizes the DNA methylation patterns specific to fragile X syndrome (FXS) with a full mutation (FM > 200 CGGs), premutation (PM 55-199 CGGs), and X inactivation in blood and brain tissues at the 3' boundary of the FMR1 promoter. Blood was analyzed from 95 controls and 462 individuals (32% males) with FM and PM alleles. Brain tissues (62% males) were analyzed from 12 controls and 4 with FXS. There was a significant increase in intron 1 methylation, extending to a newly defined 3' epigenetic boundary in the FM compared with that in the control and PM groups (p < 0.0001), and this was consistent between the blood and brain tissues. A distinct intron 2 site showed a significant decrease in methylation for the FXS groups compared with the controls in both sexes (p < 0.01). In all female groups, most intron 1 (but not intron 2 sites) were sensitive to X inactivation. In all PM groups, methylation at the 3' epigenetic boundary and the proximal sites was significantly decreased compared with that in the control and FM groups (p < 0.0001). In conclusion, abnormal FMR1 intron 1 and 2 methylation that was sensitive to X inactivation in the blood and brain tissues provided a novel avenue for the detection of PM and FM alleles through DNA methylation analysis.

Paternal retraction of a fragile X allele to normal size, showing normal function over two generations.

The FMR1 premutation (PM:55-199 CGG) is associated with fragile X-associated tremor/ataxia syndrome (FXTAS) and when maternally transmitted is at risk of expansion to a hypermethylated full mutation (FM: ≥ 200 CGG) that causes fragile X syndrome (FXS). We describe a maternally transmitted PM (77 CGG) that was passed to a son (103 CGG), and to a daughter (220-1822 CGG), who were affected with FXTAS and FXS, respectively. The male with the PM showed low-level mosaicism for normal size of 30 and 37 CGG. This male had two offspring: one female mosaic for PM and FM (56, 157, >200 CGG) and another with only a 37 CGG allele detected in multiple tissues, neither with a clinical phenotype. The female with the 37 CGG allele showed normal levels of FMR1 methylation and mRNA and passed this 37 CGG allele to one of her daughters, who was also unaffected. These findings show that post-zygotic paternal retraction can lead to low-level mosaicism for normal size alleles, with these normal alleles being functional when passed over two generations.

Seaweed Phenolics as Natural Antioxidants, Aquafeed Additives, Veterinary Treatments and Cross-Linkers for Microencapsulation.

Driven by consumer demand and government policies, synthetic additives in aquafeed require substitution with sustainable and natural alternatives. Seaweeds have been shown to be a sustainable marine source of novel bioactive phenolic compounds that can be used in food, animal and aqua feeds, or microencapsulation applications. For example, phlorotannins are a structurally unique polymeric phenolic group exclusively found in brown seaweed that act through multiple antioxidant mechanisms. Seaweed phenolics show high affinities for binding proteins via covalent and non-covalent bonds and can have specific bioactivities due to their structures and associated physicochemical properties. Their ability to act as protein cross-linkers means they can be used to enhance the rheological and mechanical properties of food-grade delivery systems, such as microencapsulation, which is a new area of investigation illustrating the versatility of seaweed phenolics. Here we review how seaweed phenolics can be used in a range of applications, with reference to their bioactivity and structural properties.

Association of Patient Characteristics With Postoperative Mortality in Children Undergoing Tonsillectomy in 5 US States.

Importance: The rate of postoperative death in children undergoing tonsillectomy is uncertain. Mortality rates are not separately available for children at increased risk of complications, including young children (aged <3 y) and those with sleep-disordered breathing or complex chronic conditions. Objective: To estimate postoperative mortality following tonsillectomy in US children, both overall and in relation to recognized risk factors for complications. Design, Setting, and Participants: Retrospective cohort study based on longitudinal analysis of linked records in state ambulatory surgery, inpatient, and emergency department discharge data sets distributed by the Healthcare Cost and Utilization Project for 5 states covering 2005 to 2017. Participants included 504 262 persons younger than 21 years for whom discharge records were available to link outpatient or inpatient tonsillectomy with at least 90 days of follow-up. Exposures: Tonsillectomy with or without adenoidectomy. Main Outcome and Measures: Postoperative death within 30 days or during a surgical stay lasting more than 30 days. Modified Poisson regression with sample weighting was used to estimate postoperative mortality per 100 000 operations, both overall and in relation to age group, sleep-disordered breathing, and complex chronic conditions. Results: The 504 262 children in the cohort underwent a total of 505 182 tonsillectomies (median [IQR] patient age, 7 [4-12] years; 50.6% females), of which 10.1% were performed in young children, 28.9% in those with sleep-disordered breathing, and 2.8% in those with complex chronic conditions. There were 36 linked postoperative deaths, which occurred a median (IQR) of 4.5 (2-20.5) days after surgical admission, and most of which (19/36 [53%]) occurred after surgical discharge. The unadjusted mortality rate was 7.04 (95% CI, 4.97-9.98) deaths per 100 000 operations. In multivariable models, neither age younger than 3 years nor sleep-disordered breathing was significantly associated with mortality, but children with complex chronic conditions had significantly higher mortality (16 deaths/14 299 operations) than children without these conditions (20 deaths/490 883 operations) (117.22 vs 3.87 deaths per 100 000 operations; adjusted rate difference, 113.55 [95% CI, 51.45-175.64] deaths per 100 000 operations; adjusted rate ratio, 29.39 [95% CI, 13.37-64.62]). Children with complex chronic conditions accounted for 2.8% of tonsillectomies but 44% of postoperative deaths. Most deaths associated with complex chronic conditions occurred in children with neurologic/neuromuscular or congenital/genetic disorders. Conclusions and Relevance: Among children undergoing tonsillectomy, the rate of postoperative death was 7 per 100 000 operations overall and 117 per 100 000 operations among children with complex chronic conditions. These findings may inform decision-making for pediatric tonsillectomy.

Nutrients dynamics in water and sediment of the Bonny Estuary, Niger Delta, Nigeria.

Surface water and sediment from Bonny Estuary, Nigeria, were assessed to determine the nutrient dynamics. Nutrients (nitrates, phosphates, and total organic carbon (TOC)) and some physicochemical parameters of water samples are collected from three sampling stations along the Bonny Estuary during wet seasons (April 2017, 2018, and 2019) and dry seasons (November 2017, 2018, and 2019). Physicochemical parameters analyses were conducted in situ using Horiba water checker (Model U-10). Surface water nitrate and phosphate were analysed by APHA 4500-NO3-B Colorimetric method, while sediment nitrates and phosphate by Chemical Analysis for Ecological Matter CAEM/APHA 4500-NO3-E Colorimetric method and TOC by CAEM-Wet-Oxidation Titration method. There was no significant seasonal variation in pH, temperature, dissolved oxygen, biological oxygen demand, conductivity, and turbidity nor across the sampling stations. TDS values showed significant seasonal variation with higher values in the wet seasons. Surface water nitrate and phosphate had higher concentrations in wet seasons though within recommended limits. Conversely, nitrate, phosphate, and TOC in the sediments were quite high, with higher values in wet seasons, especially the downstream of the estuary. The high levels of nutrients in the sediments as opposed to surface water could be a result of rapid deposition of nutrients which could lead to possible nutrient enrichment of the sediment. Nutrient levels in the sediment have increased fourfold over the study period. This suggests an influx of nutrients into the estuary, due to human activities. Nutrient enrichment could result in deterioration in aquatic water quality and pose a threat to the ecology of the estuary.

Is the treatment weak or the test insensitive: Interrogating item difficulties to elucidate the nature of reading intervention effects.

Intervention research in education is sometimes criticized for the use of experimenter developed assessments, especially when these are over aligned with treatment. At the same time, intervention researchers sometimes prefer locally developed assessments because they appear to be more sensitive to treatment effects even when the test is not subject to the criticism of over alignment. This paper examines the question of test sensitivity to treatment effects for experimenter developed and standardized tests for the specific case of reading in grade 8. We examine similarities and differences between a specific experimenter developed test and widely used standardized reading assessment. Analyses show these particular tests to be quite comparable. The paper concludes with an examination of test sensitivity by simulating treatment effects of different magnitudes. These analyses highlight some potential limitations of the standardized test for detecting small to moderate effects depending on the ability range of the students participating in intervention. The implications for intervention research and identification of students under response to intervention are discussed.

What Promotes Surgeon Practice Change? A Scoping Review of Innovation Adoption in Surgical Practice.

OBJECTIVE: The goal of this scoping review was to summarize the literature on facilitators and barriers to surgical practice change. This information can inform research to implement best practices and evaluate new surgical innovations. BACKGROUND: In an era of accelerated innovations, surgeons face the difficult decision to either acknowledge and implement or forgo new advances. Although changing surgical practice to align with evidence is an imperative of health systems, evidence-based guidelines have not translated into consistent change. The literature on practice change is limited and has largely focused on synthesizing information on methods and trials to evaluate innovative surgical interventions. No reviews to date have grounded their analysis within an implementation science framework. METHODS: A systematic review of the literature on surgical practice change was performed. Abstracts and full-text articles were reviewed for relevance using inclusion and exclusion criteria and data were extracted from each article. Cited facilitators and barriers were then mapped across domains within the implementation science Theoretical Domains Framework and expanded to the Capability, Opportunity, Motivation, and Behavior model. RESULTS: Components of the Capability, Opportunity, Motivation, and Behavior model were represented across the Theoretical Domains Framework domains and acted as both facilitators and barriers to practice change depending on the circumstances. Domains that most affected surgical practice change, in order, were: opportunity (environmental context and resources and social influences), capability (knowledge and skills), and motivation (beliefs about consequences and reinforcement). CONCLUSIONS: Practice change is predicated on a conducive environment with adequate resources, but once that is established, the surgeon's individual characteristics, including skills, motivation, and reinforcement determine the likelihood of successful change. Deficiencies in the literature underscore the need for further study of resource interventions and the role of surgical team dynamics in the adoption of innovation. A better understanding of these areas is needed to optimize our ability to disseminate and implement best practices in surgery.

Fragile X syndrome full mutation in cognitively normal male identified as part of an Australian reproductive carrier screening program.

Fragile X syndrome (FXS) is caused by CGG expansions of ≥200 repeats (full mutation: FM). Typically, FM causes abnormal methylation of the FMR1 promoter and silencing of FMR1, leading to reduction of FMRP, a protein essential for normal neurodevelopment. However, if unmethylated, these alleles cause over-expression of FMR1 mRNA which has been associated with Fragile X Tremor and Ataxia Syndrome (FXTAS), a late onset disorder. This report details the molecular and clinical profile of an asymptomatic male (29 years) identified as a result of cascade testing who was found to have a rare unmethylated FM (UFM) allele, as well as premutation (PM: 55-199 CGG) size alleles in multiple tissues. Full-scale IQ was within the normal range and minimal features of autism were observed. Southern blot analysis identified FM smears in blood (220-380 CGG) and saliva (212-378 CGG). A PM of 159 CGG was identified in blood and saliva. FMR1 promoter methylation analysis showed all alleles to be unmethylated. FMR1 mRNA levels were greater than fivefold of median levels in typically developing controls and males with FXS mosaic for PM and FM alleles. Issues raised during genetic counseling related to risk for FXTAS associated with UFM and elevated FMR1 mRNA levels, as well as, reproductive options, with implications for future practice.