SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.

Trends in leadership at shoulder and elbow fellowships: a cross-sectional demographic review.

OBJECTIVE: To determine educational characteristics, trends, and demographics among shoulder and elbow fellowship leaders (FLs). BACKGROUND: Fellowship leaders in shoulder and elbow impart lasting impact on trainees and field development. Four previous studies have analyzed the characteristics and career path trends among orthopedic surgery subspecialty FLs (spine, adult reconstruction, trauma, and sports medicine). We characterized the educational backgrounds and demographic composition of all 40 FLs including fellowship directors (FD), fellowship co-directors (co-FD), and associate fellowship directors (associate FD) of 31 American Shoulder and Elbow Surgeons (ASES)-accredited shoulder and elbow fellowships in the United States. We additionally compiled the residency and fellowship institutions that trained FLs as framework for aspiring leaders in orthopedic surgery. METHODS: Using the American Shoulder and Elbow Surgeons (ASES) directory website page "ASES-Recognized Shoulder and Elbow Fellowship Programs," we identified all active shoulder and elbow fellowships within the United States as well as associated FL identifiers. Compiled data points include age, sex, ethnicity, residency/fellowship training location, time since education completion until FL appointment, length in FL role, personal research Scopus H-index, and major society and journal leadership position history. RESULTS: We analyzed data from all 40 active FLs across 31 ASES-accredited shoulder and elbow fellowships, encompassing 26 FDs, 13 co-FDs, and 1 associate FD. The majority of FLs (97.5%) were male whereas 2.5% were female, with racial/ethnic identification of 80.0% Caucasian, 10.0% Asian/Pacific Islander, and 10.0% Middle Eastern. The mean Scopus H-index of the FLs was 24.63 ± 16.43. The top residency programs for producing future FLs were the University of Pittsburgh, University of Pennsylvania, University of Nebraska/Creighton, Hospital for Special Surgery, and Brown University (all n = 2). The top fellowship programs for producing future FLs were Mayo Clinic (n = 6), Columbia University (n = 6), San Francisco/California Pacific (n = 4), and Washington University in St Louis (n = 4). CONCLUSION: Shoulder and elbow fellowship leaders graduate with increased frequency from certain fellowship programs with lesser correlation to residency institutions. Programs demonstrate high retention of prior trainees as future FLs. All FLs are distinguished by high indices of research productivity; however, demographic diversity remains limited, which is comparable to prior orthopedic subspecialty FL investigations.

Vocabulary in dialogic reading: implications for AAC.

Shared reading is an important context for the development of communication, language, and literacy skills in young children. Research conducted with children who require augmentative and alternative communication has indicated that dialogic reading techniques utilized in shared reading can aid in the development of communication skills. One area that has not been investigated is which words children should have access to when engaging in these types of activities. This study reports the results of an investigation focused on the words 5-year-old children without disabilities said during a dialogic reading procedure that occurred with two books, Corduroy and Whistle for Willie. When reading Corduroy and Whistle for Willie, 59 common words said when reading each book accounted for 62.45% and 64.83% of the total words said, respectively. Many of these words were similar to those identified in studies of core vocabulary across a variety of contexts. For Corduroy and Whistle for Willie, 13 and 11 of these 59 words were directly related to the book, respectively. This accounted for approximately 10% of the most commonly used words for each book. The implications of this finding are discussed relative to vocabulary selection for children with complex communication needs during shared reading experiences.

The impact of image resolution on power, bias, and confounding: A simulation study of ambient light at night exposure.

Studies of the impact of environmental pollutants on health outcomes can be compromised by mismeasured exposures or unmeasured confounding with other environmental exposures. Both problems can be exacerbated by measuring exposure from data sources with low spatial resolution. Artificial light at night, for example, is often estimated from low-resolution satellite images, which may result in substantial measurement error and increased correlation with air or noise pollution. METHODS: Light at night exposure was considered in simulated epidemiologic studies in Vancouver, British Columbia. First, we assessed statistical power and bias for hypothetical studies that replaced true light exposure with estimates from sources with low resolution. Next, health status was simulated based on pollutants other than light exposure, and we assessed the frequency with which studies might incorrectly attribute negative health impacts to light exposure as a result of unmeasured confounding by the other environmental exposures. RESULTS: When light was simulated to be the causal agent, studies relying on low-resolution data suffered from lower statistical power and biased estimates. Additionally, correlations between light and other pollutants increased as the spatial resolution of the light exposure map decreased, so studies estimating light exposure from images with lower spatial resolution were more prone to confounding. CONCLUSIONS: Studies estimating exposure to pollutants from data with lower spatial resolution are prone to increased bias, increased confounding, and reduced power. Studies examining effects of light at night should avoid using exposure estimates based on low-resolution maps, and should consider potential confounding with other environmental pollutants.

Incorporating partial adherence into the principal stratification analysis framework.

Participants in pragmatic clinical trials often partially adhere to treatment. However, to simplify the analysis, most studies dichotomize adherence (supposing that subjects received either full or no treatment), which can introduce biases in the results. For example, the popular approach of principal stratification is based on the concept that the population can be separated into strata based on how they will react to treatment assignment, but this framework does not include strata in which a partially adhering participant would belong. We expanded the principal stratification framework to allow partial adherers to have their own principal stratum and treatment level. The expanded approach is feasible in pragmatic settings. We have designed a Monte Carlo posterior sampling method to obtain the relevant parameter estimates. Simulations were completed under a range of settings where participants partially adhered to treatment, including a hypothetical setting from a published simulation trial on the topic of partial adherence. The inference method is additionally applied to data from a real randomized clinical trial that features partial adherence. Comparison of the simulation results indicated that our method is superior in most cases to the biased estimators obtained through standard principal stratification. Simulation results further suggest that our proposed method may lead to increased accuracy of inference in settings where study participants only partially adhere to assigned treatment.

School-Based Speech-Language Pathologists: Confidence in Augmentative and Alternative Communication Assessment.

Purpose The purpose of this study was to examine confidence levels and identify predictors of increased confidence of school-based speech-language pathologists (SLPs) relative to different aspects of the augmentative and alternative communication (AAC) assessment process. Method Surveys were completed by 272 school-based SLPs. Questions were designed to capture demographic information and confidence in areas of assessment such as student capabilities, participation, and feature matching. Results There were variable levels of confidence across aspects of assessment. Respondents were less confident in tasks related to assessing students with severe physical impairments and incorporating aspects related to cultural and linguistic diversity in their assessment. SLPs were more confident assessing student participation and unaided communication. Additionally, respondents had less confidence in matching the features of high-tech speech-generating devices to their students. Self-identification as an AAC specialist, years of experience, percentage of caseload of students with complex communication needs, and length of longest continuing education experiences all contributed to predicting confidence in most areas of assessment. However, years of experience did not contribute to predicting confidence in feature matching. Conclusions Results from this study acknowledge that SLPs are likely to have varied degrees of confidence in aspects of assessment related to preparation, clinical experience, and self-identification of specialty. Findings from this study support increasing training opportunities in AAC assessment. As specialization was the strongest predictor of confidence, further research should investigate the characteristics and preparation of self-identified AAC specialists. This is an important first step in pinpointing ways to increase confidence in school-based SLPs.

Outdoor light at night at residences and breast cancer risk in Canada.

Experimental and epidemiologic studies suggest that light at night (LAN) exposure disrupts circadian rhythm, and this disruption may increase breast cancer risk. We investigated the potential association between residential outdoor LAN and breast cancer risk. A population-based case-control study was conducted in Vancouver, British Columbia and Kingston, Ontario, Canada with incident breast cancer cases, and controls frequency matched by age in the same region. This analysis was restricted to 844 cases and 905 controls who provided lifetime residential histories. Using time-weighted average duration at each home 5-20 years prior to study entry, two measures of cumulative average outdoor LAN were calculated using two satellite data sources. Logistic regression was used to estimate the relationship between outdoor LAN and breast cancer risk, considering interactions for menopausal status and night shift work. We found no association between residential outdoor LAN and breast cancer for either measure of LAN [OR comparing highest vs. lowest tertile (DNB) = 0.95, 95% CI 0.70-1.27]. We also found no association when considering interactions for menopausal status and past/current night work status. These findings were robust to changes to years of residential data considered, residential mobility, and longer exposure windows. Our findings are consistent with studies reporting that outdoor LAN has a small effect or no effect on breast cancer risk.

TARGETED RESEQUENCING OF WETLAND SEDIMENT AS A TOOL FOR AVIAN INFLUENZA VIRUS SURVEILLANCE.

Surveillance methods for avian influenza virus (AIV) based upon collecting and testing samples from individual wild birds have several significant limitations primarily related to the difficulties associated with obtaining samples. Because AIVs are shed in waterfowl feces, the use of environmental substrates where waterfowl feces accumulate may overcome some of these limitations. However, these substrates are difficult to analyze using traditional diagnostic techniques, such as virus culture and PCR, because of virus inactivation, RNA degradation, low concentration of target RNA, microbial complexity, presence of inhibitory substances, and other factors. We investigated the use of a genomics-based approach called targeted resequencing to detect and characterize AIVs in wetland sediments during the 2014-15 North American highly pathogenic avian influenza outbreak. We identified AIV in 20.6% (71/345) sediment samples obtained from wetlands (n=15) and outdoor waterbodies on AIV-infected poultry farms (n=10) in British Columbia, Canada (the first area affected during the outbreak). Thirteen hemagglutinin (HA) and nine neuraminidase (NA) subtypes were detected, including H5, N1, and N8 sequences that clustered with other sequences associated with the North American outbreak. Additionally, as many as eight HA and eight NA subtypes could be detected in a single sediment sample. This proof-of-concept study shows the potential utility of sediment sampling coupled with genomics-based analysis as a tool for AIV surveillance.

Wh - Question answering in children with intellectual disability.

This study investigated the ability of students with intellectual disability (ID) (n = 39) to answer questions beginning with different wh- question words presented in two referential conditions (i.e., with and without a picture). It also investigated participants' ability to answer questions that were more concrete (i.e., who, what, where) or abstract (i.e., when, why, how). Across conditions, the rank ordering of correct responses for each question word was: what, who, where, how, why, when. Logistic regression analysis revealed no overall statistical significance between the probability of answering questions correctly across referential conditions. Participants answered 89% of concrete and 56% of abstract questions correctly across both referential conditions, and logistic regression analysis revealed a statistically significant difference between the probability of answering concrete and abstract questions. The results of this study point to the importance of learning more about ways to support students with ID with answering wh- questions.

Influence of Pedaling Cadence and Incremental Protocol on the Estimation of EMGFT.

Duff, TM, Fournier, H, Hopp, OB, Ochshorn, E, Sanders, ES, Stevens, RE, and Malek, MH. Influence of pedaling cadence and incremental protocol on the estimation of EMGFT. J Strength Cond Res 30(8): 2206-2211, 2016-Theoretically, the electromyographic fatigue threshold (EMGFT) is the highest exercise intensity that an individual can exercise at indefinitely without an increase in electromyography (EMG) amplitude. This index is estimated from a single incremental test. There are, however, factors that may influence EMG amplitude such as pedaling cadence or the incremental protocol used. The purposes of this study were to determine whether different pedaling cadences and/or incremental protocols influence the estimation of the EMGFT. Eight healthy college-aged men performed incremental cycle ergometry on three separate visits. The participants exercised using the following combinations of pedaling cadences and incremental protocols in random order: 25 W at 70 RPM; 13 W at 70 RPM; and 25 W at 100 RPM. The EMGFT value was determined from the vastus lateralis muscle of each participant for each of the three conditions. Separate 1-way repeated measures analysis of variances were performed to determine mean differences for various outcome indices. The mean maximal power output for the 13 W at 70 RPM condition was significantly lower than the two other conditions. There were, however, no significant mean differences (F (2,14) = 2.03; p = 0.169) for EMGFT between the three conditions. The findings of this study indicated that different pedaling cadences and incremental protocols did not influence the estimation of the EMGFT.

The questions verbal children with autism spectrum disorder encounter in the inclusive preschool classroom.

This study investigated questions adults asked to children with autism spectrum disorder in inclusive pre-kindergarten classrooms, and whether child (e.g. autism severity) and setting (i.e. adult-to-child ratio) characteristics were related to questions asked during center-time. Videos of verbal children with autism spectrum disorder (n = 42) were coded based on the following question categories adapted from the work of Massey et al.: management, low cognitive challenging, or cognitively challenging. Results indicated that management questions (mean = 19.97, standard deviation = 12.71) were asked more than less cognitively challenging questions (mean = 14.22, standard deviation = 8.98) and less cognitively challenging questions were asked more than cognitively challenging questions (mean = 10.00, standard deviation = 6.9). Children with higher language levels had a greater likelihood of receiving cognitively challenging questions (odds ratio = 1.025; p = 0.007). Cognitively challenging questions had a greater likelihood of being asked in classrooms with more adults relative to children (odds ratio = 1.176; p = 0.037). The findings present a first step in identifying the questions directed at preschoolers with autism spectrum disorder in inclusive classrooms.

Arthroscopic Excision of a Symptomatic Os Trigonum.

PURPOSE: To report the clinical outcomes of arthroscopic excision for a symptomatic os trigonum initially viewing through the posteromedial ankle portal with the motorized instrument in the posterolateral portal. METHODS: A retrospective review of a consecutive series of patients with symptomatic os trigonum failing nonoperative management and treated with arthroscopic excision was performed. Demographic data, clinical data, American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot scores, and Single Assessment Numeric Evaluation scores were obtained. Any complications and the time required to return to sports or full activities were recorded. RESULTS: Twenty-four patients with an arthroscopic excision of a symptomatic os trigonum were included. There were 13 male and 11 female patients. The average age was 36.7 ± 17 years. Twenty-one isolated os trigonum excisions and 3 excisions combined with other procedures were studied. At a mean follow-up of 26 months (range, 24 to 31 months), average preoperative AOFAS scores significantly improved from 55.3 to 92.3 postoperatively (P < .0001). The preoperative AOFAS function component improved from 17.1 to 33.8 (P < .0001). The mean postoperative Single Assessment Numeric Evaluation score was 90. Patients reported full activity at an average of 1.5 months with no limitations at an average of 7.8 months after surgery. The only complication was a posterior tibial nerve calcaneal branch neurapraxia. CONCLUSIONS: Arthroscopic excision in the prone position without traction of a symptomatic os trigonum viewing initially through the posteromedial portal with a high-speed burr in the posterolateral portal resulted in significantly improved AOFAS scores with a single transient neurapraxia in 24 patients. Patients returned to their normal daily activities without limitations at an average of 1.5 months. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Subtle lisfranc subluxation: results of operative and nonoperative treatment.

Subtle Lisfranc instability is typically a low-energy, twisting, axial-loading injury. The present study evaluated the operative treatment of subtle Lisfranc injuries after nonoperative failure. The data from consecutive patients with subtle Lisfranc instabilities were reviewed. Those in whom initial nonoperative treatment had failed underwent surgery. The American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score was obtained initially, after nonoperative treatment, and, for those in whom nonoperative treatment had failed, after operative treatment. Of 36 patients enrolled, 16 (44.44%) were successfully treated nonoperatively, and 20 (55.56%) required surgery after nonoperative treatment had failed. Of those treated operatively, 9 (45%) were stabilized with dual screws and 11 (55%) with dual suture buttons. The mean follow-up period was 36 ± 12.2 months. The AOFAS scores significantly improved from the pre- to final post-treatment values. The overall mean pretreatment AOFAS score (62.8 ± 8.84) was significantly lower statistically than the mean overall post-treatment AOFAS score (91.3 ± 8.34; p < .0001). The mean AOFAS score before nonoperative treatment (61.9 ± 9.5) improved to a mean AOFAS score of 75.3 ± 15.8 after nonoperative treatment (p = .0029). The mean preoperative AOFAS score (63.5 ± 8.46) improved to a postoperative AOFAS score of 92.3 ± 8.43 (p < .0001). The mean AOFAS score before nonoperative treatment (61.9 ± 9.5) was not significantly different statistically from the mean preoperative AOFAS score (63.5 ± 8.46; p = .62). The mean AOFAS score after nonoperative treatment (75.3 ± 15.8) was lower than the mean postoperative AOFAS score (92.3 ± 8.43; p < .0001). Of the 9 feet stabilized with dual screws, 7 (77.78%) required screw removal during the observation period. Subtle Lisfranc injuries failing nonoperative treatment were successfully stabilized using either a dual screw or suture button technique.

Revision rates after anterior cruciate ligament reconstruction using bone-patellar tendon-bone allograft or autograft in a population 25 years old and younger.

PURPOSE: To compare clinical outcomes and revision rates for anterior cruciate ligament (ACL) reconstructions using bone-patellar tendon-bone (BPTB) allografts versus BPTB autografts in a population of patients aged 25 years and younger. METHODS: A consecutive series of patients 25 years or younger undergoing ACL reconstruction with either a patient-selected BPTB allograft or BPTB autograft fixed with biocomposite interference screws was retrospectively reviewed. Multiligamentous and posterior cruciate ligament tears were excluded. All allografts were from a single source and not chemically processed or irradiated. Two graft-specific rehabilitation programs were used. The primary outcome measure was graft failure. Failure was defined as a subsequent ACL revision surgery, 2+ Lachman test, positive pivot-shift, or side-to-side KT difference of greater than 5 mm. Secondary outcome measures included Cincinnati, Lysholm, and International Knee Documentation Committee (IKDC) activity scores. RESULTS: In 81 patients at least 24 months after surgery (28 allografts; 53 autografts), 7 failures were identified: 2 of 28 (7.1%) allografts and 5 of 53 (9.4%) autografts. Mean Cincinnati scores improved from 54.6 and 39.5 (allografts and autografts, respectively) to 86.2 and 85.1. Mean Lysholm scores improved from 60.3 and 44.8 (allografts and autografts, respectively) to 89.9 and 87.0. Average KT differences were 0.59 mm (allograft) and 0.34 mm (autograft group) (P = .58). IKDC activity scores were 2.9 (allografts) and 3.1 (autografts) postoperatively (P = .32). CONCLUSIONS: Using a patient-choice ACL graft selection program after appropriate counseling and using graft-specific rehabilitation programs, not chemically processed or irradiated BPTB allograft reconstructions have no greater failure rate than autografts in patients aged 25 years and younger at a minimum 2-year follow-up. No significant differences in Cincinnati, Lysholm, and IKDC activity scores were found between these 2 groups. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Adverse events associated with biodegradable lactide-containing suture anchors.

PURPOSE: To evaluate the occurrence of adverse events and inflammatory reactions related to the use of biodegradable anchors. METHODS: A retrospective review of a consecutive series of arthroscopic shoulder procedures using biodegradable suture anchors performed by a single surgeon was undertaken. The database was purged of patient identifiers. The blinded data were analyzed for procedure type, anchor type and composition, associated procedures, and general demographic data. Anchor composition and number were recorded. A shoulder procedure after the index operation was considered an adverse event. The nature of these procedures was evaluated using medical records, operative images, and video, looking specifically for inflammatory reactions. Any anchor-related issues were documented. RESULTS: Three hundred sixty cases met the inclusion criteria. The procedure was a tendon repair (rotator cuff or biceps) in 265 cases and a labral repair (instability or SLAP) in 97, 2 of which were combined instability and tendon repairs. Nine different biodegradable anchors were identified, possessing 4 different polymer combinations. Adverse events (reoperations) were identified in 18 of 360 patients (5%): 13 tendon repairs and 5 labral/instability repairs. Only 2 were anchor related. In 1 tendon repair case, the anchor broke and an anchor fragment required removal. In 1 labral repair case, the anchor eyelet (a suture) loosened from the anchor body and eroded the humeral head. No cases of inflammatory synovitis were observed. No statistical difference in adverse event rates existed between tendon and labral repairs (P > .05). CONCLUSIONS: Anchor-specific adverse events occurred in 2 of 360 procedures (0.5%). One was anchor design related (the prominent head containing the suture eyelet broke off) in a poly-L-lactic acid (PLLA) anchor. One was anchor material related and occurred when the poly-levo (70%)/dextro (30%)-lactide anchor body reabsorbed, loosening the encased eyelet suture and allowing this suture to migrate into the joint. No inflammatory reactions were documented in the slowly degrading pure PLLA or more rapidly degrading biocomposite PLLA/ß-tricalcium phosphate-based anchors. LEVEL OF EVIDENCE: Level IV, retrospective review, therapeutic study.