A Systematic Review of Advanced Sensor Technologies for Non-Destructive Testing and Structural Health Monitoring.

This paper reviews recent advances in sensor technologies for non-destructive testing (NDT) and structural health monitoring (SHM) of civil structures. The article is motivated by the rapid developments in sensor technologies and data analytics leading to ever-advancing systems for assessing and monitoring structures. Conventional and advanced sensor technologies are systematically reviewed and evaluated in the context of providing input parameters for NDT and SHM systems and for their suitability to determine the health state of structures. The presented sensing technologies and monitoring systems are selected based on their capabilities, reliability, maturity, affordability, popularity, ease of use, resilience, and innovation. A significant focus is placed on evaluating the selected technologies and associated data analytics, highlighting limitations, advantages, and disadvantages. The paper presents sensing techniques such as fiber optics, laser vibrometry, acoustic emission, ultrasonics, thermography, drones, microelectromechanical systems (MEMS), magnetostrictive sensors, and next-generation technologies.

A Systematic Review of Optimization Algorithms for Structural Health Monitoring and Optimal Sensor Placement.

In recent decades, structural health monitoring (SHM) has gained increased importance for ensuring the sustainability and serviceability of large and complex structures. To design an SHM system that delivers optimal monitoring outcomes, engineers must make decisions on numerous system specifications, including the sensor types, numbers, and placements, as well as data transfer, storage, and data analysis techniques. Optimization algorithms are employed to optimize the system settings, such as the sensor configuration, that significantly impact the quality and information density of the captured data and, hence, the system performance. Optimal sensor placement (OSP) is defined as the placement of sensors that results in the least amount of monitoring cost while meeting predefined performance requirements. An optimization algorithm generally finds the "best available" values of an objective function, given a specific input (or domain). Various optimization algorithms, from random search to heuristic algorithms, have been developed by researchers for different SHM purposes, including OSP. This paper comprehensively reviews the most recent optimization algorithms for SHM and OSP. The article focuses on the following: (I) the definition of SHM and all its components, including sensor systems and damage detection methods, (II) the problem formulation of OSP and all current methods, (III) the introduction of optimization algorithms and their types, and (IV) how various existing optimization methodologies can be applied to SHM systems and OSP methods. Our comprehensive comparative review revealed that applying optimization algorithms in SHM systems, including their use for OSP, to derive an optimal solution, has become increasingly common and has resulted in the development of sophisticated methods tailored to SHM. This article also demonstrates that these sophisticated methods, using artificial intelligence (AI), are highly accurate and fast at solving complex problems.

Structural Health Monitoring in Composite Structures: A Comprehensive Review.

This study presents a comprehensive review of the history of research and development of different damage-detection methods in the realm of composite structures. Different fields of engineering, such as mechanical, architectural, civil, and aerospace engineering, benefit excellent mechanical properties of composite materials. Due to their heterogeneous nature, composite materials can suffer from several complex nonlinear damage modes, including impact damage, delamination, matrix crack, fiber breakage, and voids. Therefore, early damage detection of composite structures can help avoid catastrophic events and tragic consequences, such as airplane crashes, further demanding the development of robust structural health monitoring (SHM) algorithms. This study first reviews different non-destructive damage testing techniques, then investigates vibration-based damage-detection methods along with their respective pros and cons, and concludes with a thorough discussion of a nonlinear hybrid method termed the Vibro-Acoustic Modulation technique. Advanced signal processing, machine learning, and deep learning have been widely employed for solving damage-detection problems of composite structures. Therefore, all of these methods have been fully studied. Considering the wide use of a new generation of smart composites in different applications, a section is dedicated to these materials. At the end of this paper, some final remarks and suggestions for future work are presented.

Quality of life, satisfaction with life, and functional mobility of young adults with arthrogryposis after leaving pediatric care.

The aim of this study was to describe satisfaction and quality of life (QOL) of young adults with arthrogryposis after leaving pediatric care. Twenty-three adults with arthrogryposis multiplex congenital (AMC) followed at a single pediatric orthopedic hospital (average age 23.6 years; range 18-36 years; 9 males, 14 females) completed questionnaires related to demographics, mobility, and activities of daily living. The Patient Reported Outcomes Measure Information System and Satisfaction with Life Scale were utilized to evaluate QOL and life satisfaction. Eighty-three percent reported general health as good/excellent, 30% lived independently, 69% were ambulatory in the community, and 57% were employed. QOL scores for physical function were lower, but other QOL scores were consistent with the general U.S. population. Average pain intensity was mild at 2.6 out of 10, with pain frequently reported in the legs and feet. Fifty-six percent were satisfied to extremely satisfied with life. Five individuals who were dissatisfied with life also reported lower physical function, higher anxiety, depression and fatigue, and pain in multiple joints. Although most young adults with AMC presented with mild pain and limitations in physical function; overall, they reported good QOL. Findings from the current study will help clinicians anticipate the needs of individuals with AMC as they transition from pediatric to adult care.

A Long-term Follow-up of Young Adults With Idiopathic Clubfoot: Does Foot Morphology Relate to Pain?

BACKGROUND: Individuals with clubfoot, treated in infancy with either the Ponseti method or comprehensive clubfoot release, often encounter pain as adults. Multiple studies have characterized residual deformity after Ponseti or surgical correction using physical exam, radiographs and pedobarography; however, the relationship between residual foot deformity and pain is not well defined. The purpose of the current study was 2-fold: (1) to evaluate the relationship between foot morphology and pain for young adults treated as infants for idiopathic clubfoot and (2) to describe and compare pedobarographic measures and outcome measures of pain and morphology among surgically treated, Ponseti treated, and typically developing feet. METHODS: We performed a case-control study of individuals treated for clubfoot at 2 separate institutions with either the Ponseti method or comprehensive clubfoot release between 1983 and 1987. All subjects (24 treated with comprehensive clubfoot release, 18 with Ponseti method, and 48 controls) were evaluated using the International Clubfoot Study Group (ICFSG) morphology scoring, dynamic pedobarography, and foot function index surveys. During pedobarography, we collected the subarch angle and arch index as well as the center of pressure progression (COPP) on all subjects. RESULTS: Foot morphology (ICFSG) scores were highly correlated with foot function index pain scores (r=0.43; P<0.001), although the difference in pain scores between the surgical and Ponseti group did not reach significance. The surgical group exhibited greater subarch angle and arch indexes than the Ponseti group, demonstrating a significant difference in morphology, a flatter foot. Finally, we found more abnormalities in foot progression, decreased COPP in the forefoot and increased COPP in the midfoot and hindfoot, in the surgical group compared with controls. CONCLUSIONS: Measures of foot morphology were correlated with pain among all treated for clubfoot. Compared with Ponseti method, comprehensive surgical release lead to greater long-term foot deformity, flatter feet and greater hindfoot loading time. LEVEL OF EVIDENCE: Level III-Therapeutic.

Variation in kinematic and spatiotemporal gait parameters by Gross Motor Function Classification System level in children and adolescents with cerebral palsy.

AIM: The aim of this study was to examine differences in gait kinematics and spatiotemporal parameters in ambulatory children and adolescents with bilateral spastic cerebral palsy (BSCP) among Gross Motor Function Classification System (GMFCS) levels I-III. METHOD: A retrospective review was conducted of individuals with BSCP who had three-dimensional motion analysis (3DGA) at one of seven pediatric hospitals. Means and standard deviations of each gait parameter were stratified by GMFCS levels (I-III) and for a typically developing comparison group. RESULTS: Data from 292 children and adolescents with BSCP (189 males, 103 females; mean age 13 y) were compared to a typically developing comparison group (24 male, 26 female; mean age 10 y 6 mo). Gait patterns differed from typically developing in all GMFCS levels, with increasing deviation as GMFCS level increased in 21 out of 28 parameters. Despite significant differences in selected mean kinematic parameters among GMFCS levels such as knee angle at initial contact of 24°, 29°, and 41° in GMFCS levels I, II and III respectively, there was also substantial overlap among GMFCS levels. INTERPRETATION: GMFCS levels cannot be identified using specific gait kinematics. Treatment decisions should be guided by comprehensive 3DGA that allows measurement of gait impairments at the joint level for each individual.

Accuracy of skinfold and bioelectrical impedance assessments of body fat percentage in ambulatory individuals with cerebral palsy.

AIM: This study assessed the accuracy of measurements of body fat percentage in ambulatory individuals with cerebral palsy (CP) from bioelectrical impedance analysis (BIA) and skinfold equations. METHOD: One hundred and twenty-eight individuals (65 males, 63 females; mean age 12y, SD 3, range 6-18y) with CP (Gross Motor Function Classification System [GMFCS] levels I (n=6), II (n=46), and III (n=19) participated. Body fat percentage was estimated from (1) BIA using standing height and estimated heights (knee height and tibial length) and (2) triceps and subscapular skinfolds using standard and CP-specific equations. All estimates of body fat percentage were compared with body fat percentage from dual-energy X-ray absorptiometry (DXA) scans. Differences between DXA, BIA, and skinfold body fat percentage were analyzed by comparing mean differences. Agreement was assessed by Bland-Altman plots and concordance correlation coefficients (CCC). RESULTS: BMI was moderately correlated with DXA (Pearson's r=0.53). BIA body fat percentage was significantly different from DXA when using estimated heights (95% confidence intervals [CIs] do not contain 0) but not standing height (95% CI -1.9 to 0.4). CCCs for all BIA comparisons indicated good to excellent agreement (0.75-0.82) with DXA. Body fat percentage from skinfold measurements and CP-specific equations was not significantly different from DXA (mean 0.8%; SD 5.3%; 95% CI -0.2 to 1.7) and demonstrated strong agreement with DXA (CCC 0.86). INTERPRETATION: Accurate measures of body fat percentage can be obtained using BIA and two skinfold measurements (CP-specific equations) in ambulatory individuals with CP. These findings should encourage assessments of body fat in clinical and research practices.

One-Minute Walk and modified Timed Up and Go tests in children with cerebral palsy: performance and minimum clinically important differences.

AIM This prospective multicenter study assessed performance and changes over time, with and without surgical intervention, in the modified Timed Up and Go (mTUG) and One-Minute Walk tests (1MWT) in children with bilateral cerebral palsy (CP). Minimum clinically important differences (MCIDs) were established for these tools. METHOD Two hundred and nineteen participants with bilateral spastic CP (Gross Motor Function Classification System [GMFCS] levels I­III) were evaluated at baseline and 12 months follow-up. The non-surgical group (n=168; 54 females, 114 males; mean age 12y 11mo, [SD 2y 7mo], range 8y 1mo­19y) had no surgical interventions during the study. The surgical group (n=51; 19 females, 32 males; mean age 12y 10mo [SD 2y 8mo] range 8y 2mo­17y 5mo) underwent soft-tissue and/or bony procedures within 12 months from baseline. The mTUG and 1MWT were collected and MCIDs were established from the change scores of the non-surgical group. RESULTS Dependent walkers (GMFCS level III) required more time to complete the mTUG (p≤0.01) than independent walkers (GMFCS levels I and II). For the 1MWT, distance walked decreased with increasing impairment (p≤0.01). 1MWT and mTUG change scores were not significantly different at any GMFCS level for either the surgical or non-surgical groups (p≤0.01). INTERPRETATION Children with varying levels of function (GMFCS level) perform differently on the 1MWT and mTUG. The data and MCID values can assist clinicians in interpreting changes over time and in assessing interventions.

Variability explained by strength, body composition and gait impairment in activity and participation measures for children with cerebral palsy: a multicentre study.

OBJECTIVE: To determine the amount of variability in scores on activity and participation measures used to assess ambulatory individuals with cerebral palsy explained by strength, body composition, gait impairment and participant characteristics. DESIGN: Multicentre prospective cross-sectional study. SETTING: Seven paediatric-orthopaedic specialty hospitals. PARTICIPANTS: Three hundred and seventy-seven ambulatory individuals (241 males, 136 females) with cerebral palsy, Gross Motor Function Classification System (GMFCS) levels I-III (I = 148, II = 153, III = 76), ages 8-18 years (mean 12 years 9 months, SD 2 years 8 months). METHODS: Participants completed assessments of GMFCS level, patient history, lower extremity muscle strength, Gross Motor Function Measure (GMFM-66), Pediatric Outcomes Data Collection Instrument (PODCI), instrumented gait analysis, 1 minute walk test, Timed Up-and-Go and body composition. Multiple linear regression and bootstrap analyses were performed for each outcome measure, stratified by GMFCS level. RESULTS: The amount of variability in outcome measures explained by participant characteristics, strength, and gait impairment ranged from 11% to 50%. Gait impairment was the most common predictor variable and frequently explained the greatest variance across all outcome measures and GMFCS levels. As gait impairment increased, scores on outcome measures decreased. Strength findings were inconsistent and not a primary factor. Body composition contributed minimally (<4%) in explaining variability. Participant characteristics (cerebral palsy type, gestational age and age at walking onset), were significant predictor variables in several models. CONCLUSIONS: Variability in outcome measure scores is multifaceted and only partially explained by strength and gait impairment illustrating the challenges of attempting to explain variation within this heterogeneous population. Clinicians treating individuals with cerebral palsy should consider this when developing treatment paradigms.

Long-term results of comprehensive clubfoot release versus the Ponseti method: which is better?

BACKGROUND: Clubfoot can be treated nonoperatively, most commonly using a Ponseti approach, or surgically, most often with a comprehensive clubfoot release. Little is known about how these approaches compare with one another at longer term, or how patients treated with these approaches differ in terms of foot function, foot biomechanics, or quality-of-life from individuals who did not have clubfoot as a child. QUESTIONS/PURPOSES: We compared (1) focused physical and radiographic examinations, (2) gait analysis, and (3) quality-of-life measures at long-term followup between groups of adult patients with clubfoot treated either with the Ponseti method of nonsurgical management or a comprehensive surgical release through a Cincinnati incision, and compared these two groups with a control group without clubfoot. METHODS: This was a case control study of individuals treated for clubfoot at two separate institutions with different methods of treatment between 1983 to 1987. One hospital used only the Ponseti method and the other mainly used a comprehensive clubfoot release. There were 42 adults (24 treated surgically, 18 treated with Ponseti method) with isolated clubfoot along with 48 healthy control subjects who agreed to participate in a detailed analysis of physical function, foot biomechanics, and quality-of-life metrics. RESULTS: Both treatment groups had diminished strength and motion compared with the control subjects on physical examination measures; however, the Ponseti group had significantly greater ankle plantar flexion ROM (p < 0.001), greater ankle plantar flexor (p = 0.031) and evertor (p = 0.012) strength, and a decreased incidence of osteoarthritis in the ankle and foot compared with the surgical group. During gait the surgical group had reduced peak ankle plantar flexion (p = 0.002), and reduced sagittal plane hindfoot (p = 0.009) and forefoot (p = 0.008) ROM during the preswing phase compared with the Ponseti group. The surgical group had the lowest overall ankle power generation during push off compared with the control subjects (p = 0.002). Outcome tools revealed elevated pain levels in the surgical group compared with the Ponseti group (p = 0.008) and lower scores for physical function and quality-of-life for both clubfoot groups compared with age-range matched control subjects (p = 0.01). CONCLUSIONS: Although individuals in each treatment group experienced pain, weakness, and reduced ROM, they were highly functional into early adulthood. As adults the Ponseti group fared better than the surgically treated group because of advantages including increased ROM observed at the physical examination and during gait, greater strength, and less arthritis. This study supports efforts to correct clubfoot with Ponseti casting and minimizing surgery to the joints, and highlights the need to improve methods that promote ROM and strength which are important for adult function. LEVEL OF EVIDENCE: Level III, prognostic study.

The SHOnet learning health system: Infrastructure for continuous learning in pediatric rehabilitation.

Introduction: To describe the development and implementation of learning health system (LHS) infrastructure for a pediatric specialty care health system to support LHS research in pediatric rehabilitation settings. Methods: An existing pediatric common data model (eg, PEDSnet) of standardized medical terminologies for research was expanded and leveraged for this stud, and applied to SHOnet, a clinical research data resource consisting of deidentified data extracted from the electronic health record (EHR) from the Shriners Hospitals for Children speacialty pediatric health care system. We mapped EHR data for laboratory, procedures, drugs, and conditions to standardized vocabularies including ICD-10, CPT, RxNorm, and LOINC to the common data model using an established extraction-transformation-loading process. Rigorous quality checks were conducted to ensure a high degree of data conformance, completeness, and plausibility. SHOnet data elements from all sources are de-identified and the server is managed by the SHC Information Systems Department. SHOnet data are refreshed monthly and data elements are continually expanded based on new research endeavors. Interventions: Not applicable. Results: The Shriners Health Outcomes Network (SHOnet) includes data for over 10 000 distinct observational data elements based on over two million patient encounters between 2011 and present. Conclusion: The systematic process to develop SHOnet is replicable and flexible for other pediatric rehabilitation research settings interested in building out their LHS capabilities. Challenges and facilitators may arise for building such LHS infrastructure for rehabilitation in areas of (a) data capture, curation, query, and governance, (b) generating knowledge from data, and (c) dissemination and implementation of new institutional knowledge. Further research studies are needed to evaluate these data resources for scalable system-learning endeavors.SHOnet is an exemplar of an LHS for rehabilitation and specialty care settings. The success of an LHS is dependent on engagement of multiple stakeholders, shared governance, effective knowledge translation, and deep commitment to long-term strategies for engaging clinicians, administration, and families in leveraging knowledge to improve clinical outcomes.

Kyphectomy in children with myelomeningocele.

BACKGROUND: Patients with myelomeningocele and rigid lumbar and thoracolumbar kyphosis face substantial functional difficulties with sitting and lying supine and are prone to skin breakdown over the gibbus and risk of infection. Kyphectomy, along with cordotomy and segmental spinal instrumentation down to the pelvis, is one alternative that can provide reliable correction of the deformity but also can maintain that correction over a period of time. QUESTIONS/PURPOSES: We determined the fusion rates, deformity correction and maintenance, and perioperative complications of kyphectomy with long segmental spinal instrumentation using the Warner and Fackler technique. METHODS: We retrospectively reviewed the charts and radiographs of 33 patients with myelomeningocele who had kyphectomy with segmental spinal instrumentation down to the pelvis between 1991 and 2006. The average age at surgery was 7.6 years (range, 3-19 years). Twenty-one patients had a minimum 2-year followup (average, 7.0 years; range, 2.4-15.7 years). RESULTS: The average preoperative kyphosis of 124° (range, 75°-210°) improved at last followup to 22° (range, 3°-55°) with an average correction of 81% (range, 59%-98%). We identified 17 postoperative complications. Wound and skin complications were most common; 11 secondary surgeries were performed in 10 patients. CONCLUSIONS: Surgery for myelomeningocele kyphosis is technically demanding and carries substantial risk. Kyphectomy and posterior spinal fusion and instrumentation with the Warner and Fackler technique allow correction and maintenance of sagittal alignment.

Activity level, functional health, and quality of life of children with myelomeningocele as perceived by parents.

BACKGROUND: To provide the best health care for individuals with myelomeningocele (MM), clinicians and researchers need to understand their health and functional status as well as quality of life. The literature is mixed regarding the relationship between motor level and health-related quality of life (HRQOL) for these individuals. QUESTIONS/PURPOSES: We compared the HRQOL of children with MM at the L2 and above and L3-5 motor level and to demonstrate how having a shunt, age, and body mass index affect HRQOL instruments for these two motor level groups. METHODS: We recruited 50 patients with MM (24 male, 26 female) with a mean age of 11.5 years (range, 5-18 years) and motor levels of L2 and above (n = 15) and L3-5 (n = 35). Guardians were interviewed using standardized functional and HRQOL tools (the Pediatric Quality of Life and the Pediatric Outcomes Data Collection Instrument); height, weight, presence of a shunt, ambulatory level, and body mass index were also collected. RESULTS: We found a decreased HRQOL score for children with MM in the L2 and above motor level compared with those in the L3-5 motor level group. HRQOL had no correlation with body mass index and limited correlation with age. The presence of a shunt correlated with a decreased HRQOL. CONCLUSIONS: Children with MM had deficits in HRQOL and that was associated with neurologic level and presence of a shunt.

Diet and Life Stage-Associated Lipidome Remodeling in Atlantic Salmon.

Salmon is an important source of long-chain highly unsaturated fatty acids (LC-HUFAs) such as 22:6n-3 [docosahexaenoic acid (DHA)]. In the present study, we conducted two identical experiments on salmon in freshwater (FW) and seawater (SW) stages, with a diet switch from fish oil (high in LC-HUFA) to vegetable oil (low in LC-HUFA) and vice versa. Our aim was to investigate the diet and life stage-specific features of lipid uptake (gut), processing (liver), and deposition (muscle). The lipid composition changed much faster in the gut of SW fish relative to FW fish, suggesting that the former had a higher rate of lipid absorption and transport. SW fish also had higher expression of phospholipid synthesis and lipoprotein formation genes in the gut, whereas FW fish had higher expression of lipid synthesis genes in the liver. All phospholipids except PC-44:12 and PE-44:12 were less abundant in SW, suggesting that SW fish have a higher requirement for DHA.

Long-term outcome evaluation in young adults following clubfoot surgical release.

BACKGROUND: The aim of this study was to evaluate the long-term outcome of a comprehensive surgical release for congenital talipes equinovarus (CTEV). METHODS: Gait, strength, segmental foot motion, and outcomes questionnaire data were collected on 24 adults (21.8+/-2.3 y) who were surgically treated for CTEV as infants. These data were statistically compared with of 48-age group matched controls (23.2+/-2.4 y). RESULTS: The clubfoot group was functional in activities of daily living, although most patients did experience foot pain after a day of typical activities, such as walking, standing, using stairs and doing exercise. Lower extremity gait kinematics was similar to the control group. There were differences in segmental foot motion with the hindfoot in a more plantarflexed position relative to the tibia and the forefoot dorsiflexed, and adducted relative to the hindfoot. Ankle plantarflexion and inversion strength and range of motion was reduced in the clubfoot group in association with an increase in hip power generation during the preswing and initial swing phases of the gait cycle. CONCLUSIONS: Surgical correction of CTEV was successful in providing a functional plantigrade foot as the patients reached adulthood. However, limitations included foot pain, limited foot range of motion, and weakness. LEVEL OF EVIDENCE: Level III.

Ankle strength and functional limitations in children and adolescents with type I osteogenesis imperfecta.

PURPOSE: To determine whether children with type I osteogenesis imperfecta (OI) exhibit ankle plantar flexor weakness and whether this correlates with physical function. METHODS: Twenty children and adolescents with type I OI and 20 age-matched controls (age 6-18 years) participated in a single evaluation session. Data included strength assessment, Gillette Functional Assessment Questionnaire, Pediatric Outcome Data Collection Instrument (PODCI), and Faces Pain Scale-Revised. RESULTS: Ankle plantar flexor weakness was evident in the OI group compared with the control group. Heel-rise strength correlated with ankle isometric plantar flexion strength. Limitations in PODCI subscales-sports and physical function and pain/comfort-are present in the OI group. CONCLUSION: Ankle plantar flexor weakness is present in children and adolescents with type I OI and correlates with function. Gillette Functional Assessment Questionnaire, PODCI, and strength assessment are valuable evaluation tools for children and adolescents with type I OI and can aid therapists in goal setting.

Postoperative wound dehiscence after laparotomy: a useful healthcare quality indicator? A cohort study based on Norwegian hospital administrative data.

OBJECTIVES: Postoperative wound dehiscence (PWD) is a serious complication to laparotomy, leading to higher mortality, readmissions and cost. The aims of the present study are to investigate whether risk adjusted PWD rates could reliably differentiate between Norwegian hospitals, and whether PWD rates were associated with hospital characteristics such as hospital type and laparotomy volume. DESIGN: Observational study using patient administrative data from all Norwegian hospitals, obtained from the Norwegian Patient Registry, for the period 2011-2015, and linked using the unique person identification number. PARTICIPANTS: All patients undergoing laparotomy, aged at least 15 years, with length of stay at least 2 days and no diagnosis code for immunocompromised state or relating to pregnancy, childbirth and puerperium. The final data set comprised 66 925 patients with 78 086 laparotomy episodes from 47 hospitals. OUTCOMES: The outcome was wound dehiscence, identified by the presence of a wound reclosure code, risk adjusted for patient characteristics and operation type. RESULTS: The final data set comprised 1477 wound dehiscences. Crude PWD rates varied from 0% to 5.1% among hospitals, with an overall rate of 1.89%. Three hospitals with statistically significantly higher PWD than average were identified, after case mix adjustment and correction for multiple comparisons. Hospital volume was not associated with PWD rate, except that hospitals with very few laparotomies had lower PWD rates. CONCLUSIONS: Among Norwegian hospitals, there is considerable variation in PWD rate that cannot be explained by operation type, age or comorbidity. This warrants further investigation into possible causes, such as surgical technique, perioperative procedures or handling of complications. The risk adjusted PWD rate after laparotomy is a candidate quality indicator for Norwegian hospitals.

Genetic Overlap Between Alzheimer's Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes.

Background: Alzheimer's disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer's Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect). Conclusion: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP.

Effects of Spinal Fusion for Idiopathic Scoliosis on Lower Body Kinematics During Gait.

STUDY DESIGN: Prospective. OBJECTIVES: The purpose of this study was to compare gait among patients with scoliosis undergoing posterior spinal fusion and instrumentation (PSFI) to typically developing subjects and determine if the location of the lowest instrumented vertebra impacted results. SUMMARY OF BACKGROUND DATA: PSFI is the standard of care for correcting spine deformities, allowing the preservation of body equilibrium while maintaining as many mobile spinal segments as possible. The effect of surgery on joint motion distal to the spine must also be considered. Very few studies have addressed the effect of PSFI on activities such as walking and even fewer address how surgical choice of the lowest instrumented vertebra (LIV) influences possible motion reduction. METHODS: Individuals with scoliosis undergoing PSFI (n = 38) completed gait analysis preoperatively and at postoperative years 1 and 2 along with a control group (n = 24). Comparisons were made with the control group at each time point and between patients fused at L2 and above (L2+) versus L3 and below (L3-). RESULTS: The kinematic results of the AIS group showed some differences when compared to the Control Group, most notably decreased range of motion (ROM) in pelvic tilt and trunk lateral bending. When comparing the LIV groups, only minor differences were observed, and the results showed decreased coronal trunk and pelvis ROM at the one-year visit and decreased hip rotation ROM at the two-year visit in the L3- group. CONCLUSIONS: Patients with AIS showed decreased ROM preoperatively with further decreases postoperatively. These changes remained relatively consistent following the two-year visit, indicating that most kinematic changes occurred in the first year following surgery. Limited functional differences between the two LIV groups may be due to the lack of full ROM used during normal gait, and future work could address tasks that use greater ROM. LEVEL OF EVIDENCE: Level II.

Elevated expression of a minor isoform of ANK3 is a risk factor for bipolar disorder.

Ankyrin-3 (ANK3) is one of the few genes that have been consistently identified as associated with bipolar disorder by multiple genome-wide association studies. However, the exact molecular basis of the association remains unknown. A rare loss-of-function splice-site SNP (rs41283526*G) in a minor isoform of ANK3 (incorporating exon ENSE00001786716) was recently identified as protective of bipolar disorder and schizophrenia. This suggests that an elevated expression of this isoform may be involved in the etiology of the disorders. In this study, we used novel approaches and data sets to test this hypothesis. First, we strengthen the statistical evidence supporting the allelic association by replicating the protective effect of the minor allele of rs41283526 in three additional large independent samples (meta-analysis p-values: 6.8E-05 for bipolar disorder and 8.2E-04 for schizophrenia). Second, we confirm the hypothesis that both bipolar and schizophrenia patients have a significantly higher expression of this isoform than controls (p-values: 3.3E-05 for schizophrenia and 9.8E-04 for bipolar type I). Third, we determine the transcription start site for this minor isoform by Pacific Biosciences sequencing of full-length cDNA and show that it is primarily expressed in the corpus callosum. Finally, we combine genotype and expression data from a large Norwegian sample of psychiatric patients and controls, and show that the risk alleles in ANK3 identified by bipolar disorder GWAS are located near the transcription start site of this isoform and are significantly associated with its elevated expression. Together, these results point to the likely molecular mechanism underlying ANK3´s association with bipolar disorder.