rnaCrosslinkOO: an object-oriented R package for the analysis of RNA structural data generated by RNA crosslinking experiments.

SUMMARY: RNA (ribonucleic acid) molecules have secondary and tertiary structures in vivo which play a crucial role in cellular processes such as the regulation of gene expression, RNA processing and localization. The ability to investigate these structures will enhance our understanding of their function and contribute to the diagnosis and treatment of diseases caused by RNA dysregulation. However, there are no mature pipelines or packages for processing and analyzing complex in vivo RNA structural data. Here, we present rnaCrosslinkOO (RNA Crosslink Object-Oriented), a novel software package for the comprehensive analysis of data derived from the COMRADES (Crosslinking of Matched RNA and Deep Sequencing) method. rnaCrosslinkOO offers a comprehensive pipeline from raw sequencing reads to the identification and comparison of RNA structural features. It includes read processing and alignment, clustering of duplexes, data exploration, folding and comparisons of RNA structures. rnaCrosslinkOO also enables comparisons between conditions, the identification of inter-RNA interactions, and the incorporation of reactivity data to improve structure prediction. AVAILABILITY AND IMPLEMENTATION: rnaCrosslinkOO is freely available to noncommercial users and implemented in R, with the source code and documentation accessible at https://CRAN.R-project.org/package=rnaCrosslinkOO. The software is supported on Linux, macOS, and Windows platforms.

Dosimetric validation for prospective clinical trial on GRID collimator-based spatially fractionated radiation therapy: Dose metrics consistency and heterogeneous pattern reproducibility.

PURPOSE: The purpose of this study is to characterize the dosimetric properties of a commercial brass GRID collimator for high energy photon beams including 15 and 10 MV. Then, the difference in dosimetric parameters of GRID beams among different energies and linacs was evaluated. METHOD: A water tank scanning system was used to acquire the dosimetric parameters, including the percentage depth dose (PDD), beam profiles, peak to valley dose ratios (PVDRs), and output factors (OFs). The profiles at various depths were measured at 100 cm source to surface distance (SSD), and field sizes of 10 × 10 cm2 and 20 × 20 cm2 on three linacs. The PVDRs and OFs were measured and compared with the treatment planning system (TPS) calculations. RESULTS: Compared with the open beam data, there were noticeable changes in PDDs of GRID fields across all the energies. The GRID fields demonstrated a maximal of 3 mm shift in dmax (Truebeam STX, 15MV, 10 × 10 cm2). The PVDR decreased as beam energy increases. The difference in PVDRs between Trilogy and Truebeam STx using 6MV and 15MV was 1.5% ± 4.0% and 2.1% ± 4.3%, respectively. However, two Truebeam linacs demonstrated less than 2% difference in PVDRs. The OF of the GRID field was dependent on the energy and field size. The measured PDDs, PVDRs, and OFs agreed with the TPS calculations within 3% difference. The TPS calculations agreed with the measurements when using 1 mm calculation resolution. CONCLUSION: The dosimetric characteristics of high-energy GRID fields, especially PVDR, significantly differ from those of low-energy GRID fields. Two Truebeam machines are interchangeable for GRID therapy, while a pronounced difference was observed between Truebeam and Trilogy. A series of empirical equations and reference look-up tables for GRID therapy can be generated to facilitate clinical applications.

Health Care Professional Education on Cancer Screening of SGM Individuals: An Integrative Review.

Sexual and gender minority (SGM) individuals are disproportionately affected by cancer. Health care professional (HCP) and health sciences education rarely includes content on cancer screening in this population. This article aims to synthesize literature on educational programs for HCPs and health sciences students related to cancer screening for SGM individuals. An integrative review methodology guided a systematic search of five databases: CINAHL, PubMed, Embase, PsycInfo, and ERIC. Articles were included if they were empirically-based and described educational programs targeted at HCPs and health sciences students with content of cancer screening for SGM people. Eleven studies met the inclusion criteria. Of these, three were pilot studies and the majority of the articles (n = 9) used pre- and post-test designs. All of the interventions showed efficacy in increasing knowledge, attitudes, skills, and behavior. However, the vastly different programs and the fact that most of the cancer screening content was embedded in programs with broad SGM issues content limit the ability to make firm recommendations for any one particular program. In-person didactic content delivered multiple times incorporating modalities such as standardized patient encounters, case studies, and guest speakers increased knowledge, attitude, and skills of participants. Future studies should incorporate behavioral theories, develop more consistent aspects of educational programs, report demographic and pertinent data on participants, and utilize established instruments to measure outcomes when conducting educational interventions on HCPs and students in this area.

Combination of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release for patellofemoral instability provides good middle- to long-term outcomes in adolescents.

PURPOSE: There are limited studies that have reported the middle- to long-term outcomes of combined procedures consisting of more than two procedures for patellofemoral instability. The current study aims to investigate and report the middle- to long-term outcomes of a combination procedure of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release for patellofemoral instability in patients aged 18 years and below. METHODS: In the cohort study, all patients aged 18 years old or younger who underwent a combination procedure of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release for recurrent patellofemoral instability were included. RESULTS: A total of 21 patients were included in the study. All patients had no further patellofemoral dislocation, pain and apprehension following the 4-in-1 surgery (p < 0.01). There was a significant improvement in the Kujala score from 36.1 (SD 12.9) pre-operatively to 93.1 (SD 3.6) post-operatively (p < 0.001). The patients also had a statistically significant improvement in their radiological factors, including the patellar tilt angle (p < 0.001), sulcus angle (p = 0.001), trochlear groove depth (p = 0.041), tibial tubercle-trochlear groove distance (p < 0.001) and Caton-Deschamps index (p = 0.001). CONCLUSION: A combination procedure of tibial tubercle transfer, medial patellofemoral ligament reconstruction, trochleoplasty and lateral release leads to good middle- to long-term subjective, functional and radiographic outcomes for patients with recurrent patellofemoral instability and underlying predisposing factors of increased TT-TG distance of more than 20 mm, Dejour B or D trochlear dysplasia and medial patellofemoral ligament rupture. LEVEL OF EVIDENCE: IV.

Predictors and outcomes of dose reduction of methotrexate and cyclosporin graft-versus-host disease prophylaxis following allogeneic haemopoietic cell transplantation.

BACKGROUND: Concern regarding dose-related toxicities of methotrexate (MTX) and cyclosporin (CYA) graft-versus-host disease (GVHD) prophylaxis occasionally leads to dose alterations post allogeneic haemopoietic cell transplant (alloHCT). AIMS: To clarify causes of MTX and CYA dose alteration and assess impact on patient outcomes, including GVHD, relapse, non-relapse mortality (NRM) and overall survival (OS). METHODS: Analysis of retrospective data was performed in a single tertiary centre of patients who underwent alloHCT for any indication and who received GVHD prophylaxis with CYA and MTX between the years 2011 and 2015. Univariate analysis was conducted using the log-rank test for OS and using competing risk regression for NRM, relapse and GVHD. Fisher exact tests were used to determine if an association existed between each of the pre-transplant variables and MTX alteration. Multivariate models for OS and NRM were constructed using Cox proportional hazards modelling and competing risk regression respectively. RESULTS: Fifty-four (28%) of 196 had MTX alterations and 61/187 (33%) had CYA alterations. Reasons for MTX alteration included mucositis, renal or liver impairment, fluid overload and sepsis. Causes of CYA alteration were numerous, but most commonly due to acute kidney impairment. MTX alteration was associated with inferior OS (hazard ratio 2.4; P = <0.001) and higher NRM (odds ratio (OR) 4.6; P < 0.001) at 6 years post-landmark. CYA alteration was associated with greater NRM (OR 2.7; P = 0.0137) at 6 years. GVHD rates were unaffected by dose alteration. CONCLUSIONS: Our findings suggest dose alteration in MTX and CYA GVHD prophylaxis is associated with adverse survival outcomes in alloHCT, without a significant impact on GVHD rates.

Correlates of Person-Specific Rates of Change in Sensor-Derived Physical Activity Metrics of Daily Living in the Rush Memory and Aging Project.

This study characterized person-specific rates of change of total daily physical activity (TDPA) and identified correlates of this change. TDPA metrics were extracted from multiday wrist-sensor recordings from 1083 older adults (average age 81 years; 76% female). Thirty-two covariates were collected at baseline. A series of linear mixed-effect models were used to identify covariates independently associated with the level and annual rate of change of TDPA. Though, person-specific rates of change varied during a mean follow-up of 5 years, 1079 of 1083 showed declining TDPA. The average decline was 16%/year, with a 4% increased rate of decline for every 10 years of age older at baseline. Following variable selection using multivariate modeling with forward and then backward elimination, age, sex, education, and 3 of 27 non-demographic covariates including motor abilities, a fractal metric, and IADL disability remained significantly associated with declining TDPA accounting for 21% of its variance (9% non-demographic and 12% demographics covariates). These results show that declining TDPA occurs in many very old adults. Few covariates remained correlated with this decline and the majority of its variance remained unexplained. Further work is needed to elucidate the biology underlying TDPA and to identify other factors that account for its decline.

Fragmentation of rest periods, astrocyte activation, and cognitive decline in older adults with and without Alzheimer's disease.

INTRODUCTION: Sleep disruption is associated with astrocyte activation and impaired cognition in model organisms. However, the relationship among sleep, astrocyte activation, and cognition in humans is uncertain. METHODS: We used RNA-seq to quantify the prefrontal cortex expression of a panel of human activated astrocyte marker genes in 1076 older adults in the Religious Orders Study and Rush Memory and Aging Project, 411 of whom had multi-day actigraphy prior to death. We related this to rest fragmentation, a proxy for sleep fragmentation, and to longitudinal cognitive function. RESULTS: Fragmentation of rest periods was associated with higher expression of activated astrocyte marker genes, which was associated with a lower level and faster decline of cognitive function. DISCUSSION: Astrocyte activation and fragmented rest are associated with each other and with accelerated cognitive decline. If experimental studies confirm a causal relationship, targeting sleep fragmentation and astrocyte activation may benefit cognition in older adults. HIGHLIGHTS: Greater fragmentation of rest periods, a proxy for sleep fragmentation, is associated with higher composite expression of a panel of genes characteristic of activated astrocytes. Increased expression of genes characteristic of activated astrocytes was associated with a lower level and more rapid decline of cognitive function, beyond that accounted for by the burden of amyloid and neurofibrillary tangle pathology. Longitudinal and experimental studies are needed to delineate the causal relationships among sleep, astrocyte activation, and cognition.

Sex differences in associations between APOE ε2 and longitudinal cognitive decline.

INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. HIGHLIGHTS: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

Changes in the time of COVID-19: a quality improvement initiative to maintain services at a youth sexual health clinic.

OBJECTIVES: Adolescents and young adults (AYAs) face difficulties accessing sexual and reproductive health services. These difficulties were exacerbated for a variety of reasons by the COVID-19 pandemic. We document strategies and outcomes implemented at an urban youth sexual health clinic in Florida that allowed uninterrupted provision of services while protecting against spread of COVID-19. METHODS: The plan-do-study-act (PDSA) model was used to implement COVID-19 interventions designed to allow continued service delivery while protecting the health and safety of staff and patients. This method was applied to clinic operations, community referral systems and community outreach to assess and refine interventions within a quick-paced feedback loop. RESULTS: During the COVID-19 pandemic, changes made via PDSA cycles to clinical/navigation services, health communications and youth outreach/engagement effectively responded to AYA needs. Although overall numbers of youth served decreased, all youth contacting the clinic for services were able to be accommodated. Case finding rates for chlamydia, gonorrhoea, syphilis and HIV were similar to pre-pandemic levels. CONCLUSIONS: Quality improvement PDSA initiatives at AYA sexual health clinics, particularly those for underserved youth, can be used to adapt service delivery when normal operating models are disrupted. The ability for youth sexual health clinics to adapt to a changing healthcare landscape will be crucial in ensuring that under-resourced youth are able to receive needed services and ambitious Ending the HIV Epidemic goals are achieved.

Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in elderly patients with relapsed multiple myeloma: IKEMA subgroup analysis.

In this subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285), we evaluated efficacy and safety of the anti-CD38 monoclonal antibody isatuximab (Isa) in combination with carfilzomib-dexamethasone (Isa-Kd) versus Kd in older (≥70 years of age, n = 86) and younger (<70 years, n = 216) patients with relapsed multiple myeloma (MM). Patients received Isa 10 mg/kg intravenously weekly for 4 weeks, then every 2 weeks in the Isa-Kd arm, and approved schedule of carfilzomib (twice weekly) and dexamethasone in both study arms. Primary endpoint was progression-free survival (PFS); key secondary efficacy endpoints included rates of overall response (ORR), very good partial response or better (≥VGPR), minimal residual disease negativity (MRD-), and complete response (CR). Addition of Isa to Kd resulted in improved PFS in elderly patients (hazard ratio, 0.36 [95% CI, 0.18-0.75]) consistent with the significant PFS improvement observed in the overall IKEMA population. Treatment with Isa-Kd improved depth of response versus Kd, with higher rates of ≥VGPR (73.1% vs. 55.9%), MRD- (23.1% vs. 11.8%), and CR (38.5% vs. 23.5%). Although the incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was higher in Isa-Kd, the incidence of serious TEAEs was similar between arms. Fewer elderly patients definitively discontinued treatment due to TEAEs in Isa-Kd than Kd: 11.8% versus 23.5%. In conclusion, Isa-Kd provides a consistent benefit versus Kd in elderly patients, with a manageable safety profile, and represents a new treatment option for patients with relapsed MM, independent of age.

The effects of napping on night-time sleep in healthy young adults.

The discrepancies in the effects of napping on sleep quality may be due to differences in methodologies, napping behaviours, and daytime activity levels across studies. We determined whether napping behaviours and daytime activity levels are associated with night-time sleep fragmentation and sleep quality in young adults. A total of 62 healthy adults (mean [SD] age 23.5 [4.2] years) completed screening questionnaires for sleep habits, physical activity, medical and psychological history. Actigraphy was used to record sleep including naps. The fragmentation algorithm (KRA ) was applied to the actigraphic data to measure night-time sleep fragmentation. We classified participants' nap frequency as "non-nappers" (0 naps/8 days), "moderate nappers" (1-2 naps/8 days) or "frequent nappers" (≥3 naps/8 days) naps. Nap duration was defined as "short" (≤60 min) or "long" (>60 min). Naps' proximity to the night sleep episode was defined as "early" (≥7 h) and "late" (<7 h) naps. Outcome variables were night-time KRA and actigraphic sleep variables. Frequent nappers had a significantly higher KRA than moderate nappers (p < 0.01) and non-nappers (p < 0.02). Late naps were associated with poorer measures of night sleep quality versus early naps (all p ≤ 0.02). Nap duration and daytime activity were not associated with significant differences in the outcome variables (all p > 0.05). KRA correlated with sleep duration, sleep efficiency, and awakenings (r = -0.32, -0.32, and 0.53, respectively; all p < 0.05). Frequent napping and late naps may be associated with increased sleep fragmentation and poorer sleep quality, reflected in longer sleep onsets and increased awakenings. These findings have implications for public health sleep hygiene recommendations.

Isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma patients with high-risk cytogenetics: IKEMA subgroup analysis.

INTRODUCTION: The presence of high-risk chromosomal abnormalities [t(4;14), del(17p), and t(14;16)] has been linked with inferior outcomes in patients with multiple myeloma (MM). A prespecified interim analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d; Isa-Kd) significantly improved progression-free survival (PFS) versus Kd in patients with relapsed MM. This prespecified subgroup analysis of IKEMA examined efficacy and safety in patients with high-risk cytogenetics. METHODS: High-risk cytogenetics was assessed by central laboratory and patients were classified as high risk if abnormalities were present in ≥1 of the following: del(17p): 50% cutoff; t(4;14), and/or t(14;16): 30% cutoff. RESULTS: Of the randomized patients, 23.5% (Isa-Kd) and 25.2% (Kd) had ≥1 high-risk chromosomal abnormality. A PFS benefit was seen in favor of Isa-Kd for patients with standard-risk (HR 0.440; 95% CI 0.266-0.728) and high-risk cytogenetics (HR 0.724; 95% CI 0.361-1.451). Grade ≥3 treatment-emergent adverse events (TEAEs) were more common with Isa-Kd (85.7%) versus Kd (63.3%) in patients with high-risk cytogenetics; however, the incidence of serious TEAEs (64.3% vs. 66.7%) was similar. CONCLUSIONS: Isa-Kd is a new treatment option for the difficult-to-treat subgroup of patients with relapsed MM and high-risk cytogenetics.

A multicentre validation study of a smartphone application to screen hand arthritis.

BACKGROUND: Arthritis is a common condition, and the prompt and accurate assessment of hand arthritis in primary care is an area of unmet clinical need. We have previously developed and tested a screening tool combining machine-learning algorithms, to help primary care physicians assess patients presenting with arthritis affecting the hands. The aim of this study was to assess the validity of the screening tool among a number of different Rheumatologists. METHODS: Two hundred and forty-eight consecutive new patients presenting to 7 private Rheumatology practices across Australia were enrolled. Using a smartphone application, each patient had photographs taken of their hands, completed a brief 9-part questionnaire, and had a single examination result (wrist irritability) recorded. The Rheumatologist diagnosis was entered following a 45-minute consultation. Multiple machine learning models were applied to both the photographic and survey/examination results, to generate a screening outcome for the primary diagnoses of osteoarthritis, rheumatoid and psoriatic arthritis. RESULTS: The combined algorithms in the application performed well in identifying and discriminating between different forms of hand arthritis. The algorithms were able to predict rheumatoid arthritis with accuracy, precision, recall and specificity of 85.1, 80.0, 88.1 and 82.7% respectively. The corresponding results for psoriatic arthritis were 95.2, 76.9, 90.9 and 95.8%, and for osteoarthritis were 77.4, 78.3, 80.6 and 73.7%. The results were maintained when each contributor was excluded from the analysis. The median time to capture all data across the group was 2 minutes and 59 seconds. CONCLUSIONS: This multicentre study confirms the results of the pilot study, and indicates that the performance of the screening tool is maintained across a group of different Rheumatologists. The smartphone application can provide a screening result from a combination of machine-learning algorithms applied to hand images and patient symptom responses. This could be used to assist primary care physicians in the assessment of patients presenting with hand arthritis, and has the potential to improve the clinical assessment and management of such patients.

Predictive Scoring for Recurrent Patellar Instability After a First-time Patellar Dislocation.

PURPOSE: Patellofemoral instability is a common acute knee injury seen in the pediatric population. First-time patellar dislocations usually undergo conservative management, but ~15% to 80% of patients experience recurrent instability. This study aims to develop a prediction model using radiographic parameters of the patellofemoral joint seen on computed tomography scans in different degrees of knee flexion, to determine the risk of recurrence after the first episode of patellofemoral instability. METHODS: A 12-year retrospective case-control study was performed. All patients in a single institution aged 18 years or younger who had a computed tomography patellar tracking scan performed for patellar instability were included. Predictors included in the score were determined through backward logistic regression and compared using receiver operating characteristic curve analysis. RESULTS: This study revealed that recurrent dislocation in first-time patellofemoral dislocation could be accurately predicted using the prediction score that consisted of age, tibial tubercle-trochlear groove distance and congruence angle at 10- and 20-degree flexion. The sensitivity of the score was 100% and specificity was 73.3%. Three diagnostic zones were identified and used to categorize patients into low-, intermediate-, and high-probability groups. CONCLUSION: This study presented a scoring system that incorporated radiographic knee kinematics in the risk assessment for recurrent patellofemoral instability for patient stratification. The scoring system could guide the decision for early surgical intervention after the first-episode patellofemoral dislocation for patients at high risk of recurrent patellofemoral dislocation.

Interobserver Variability of Hip Dysplasia Indices on Sweep Ultrasound for Novices, Experts, and Artificial Intelligence.

BACKGROUND: Ultrasound for developmental dysplasia of the hip (DDH) is challenging for nonexperts to perform and interpret. Recording "sweep" images allows more complete hip assessment, suitable for automation by artificial intelligence (AI), but reliability has not been established. We assessed agreement between readers of varying experience and a commercial AI algorithm, in DDH detection from infant hip ultrasound sweeps. METHODS: We selected a full spectrum of poor-to-excellent quality images and normal to severe dysplasia, in 240 hips (120 single 2-dimensional images, 120 sweeps). For 12 readers (radiologists, sonographers, clinicians and researchers; 3 were DDH subspecialists), and a ultrasound-FDA-cleared AI software package (Medo Hip), we calculated interobserver reliability for alpha angle measurements by intraclass correlation coefficient (ICC2,1) and for DDH classification by Randolph Kappa. RESULTS: Alpha angle reliability was high for AI versus subspecialists (ICC=0.87 for sweeps, 0.90 for single images). For DDH diagnosis from sweeps, agreement was high between subspecialists (kappa=0.72), and moderate for nonsubspecialists (0.54) and AI (0.47). Agreement was higher for single images (kappa=0.80, 0.66, 0.49). AI reliability deteriorated more than human readers for the poorest-quality images. The agreement of radiologists and clinicians with the accepted standard, while still high, was significantly poorer for sweeps than 2D images (P<0.05). CONCLUSIONS: In a challenging exercise representing the wide spectrum of image quality and reader experience seen in real-world hip ultrasound, agreement on DDH diagnosis from easily obtained sweeps was only slightly lower than from single images, likely because of the additional step of selecting the best image. AI performed similarly to a nonsubspecialist human reader but was more affected by low-quality images.

Accuracy of biplanar linear radiography versus conventional radiographs when used for lower limb and implant measurements.

INTRODUCTION: The current standard of care for measuring lower extremity length and angular discrepancies is using a full-length standing anteroposterior radiograph. However, there has been increasing interest to use biplanar linear EOS imaging as an alternative. This study aims to compare lower extremity length and implant measurements between biplanar linear and conventional radiographs. MATERIALS AND METHODS: In this 5-year retrospective study, all patients who had a standing full-length anteroposterior and biplanar linear radiographs (EOS®) that include the lower extremities done within one year of each other were included. Patients who underwent surgery in between the imaging, underwent surgeries that could result in graduated length or angulated corrections and inadequate exposure of the lower extremity were excluded. Four radiographic segments were measured to assess lower limb alignment and length measurements. Height and width measurements of implants were performed for patients who had implants in both imaging. RESULTS: When comparing imaging and actual implant dimensions, biplanar linear radiographs were accurate in measuring actual implant height (median difference = - 0.14 cm, p = 0.66), and width (median difference = - 0.13 cm, p = 0.71). However, conventional radiographs were inaccurate in measuring actual implant height (median difference = 0.19 cm, p = 0.01) and width (median difference = 0.61 cm, p < 0.01). When comparing conventional and biplanar linear radiographs, there was statistically significant difference in all measurements. This includes anatomical femoral length (median difference = 3.53 cm, p < 0.01), mechanical femoral length (median difference = 3.89 cm, p < 0.01), anatomical tibial length (median difference = 2.34 cm, p < 0.01) and mechanical tibial length (median difference = 2.20 cm, p < 0.01). CONCLUSION: First, there is a significant difference in the lower extremity length when comparing conventional and biplanar linear radiographs. Second, biplanar linear radiographs are found to be accurate while conventional radiographs are not as accurate in implant measurements of length and width in the lower extremity.

Disrupted Rest-Activity Rhythms and Cerebral Small Vessel Disease Pathology in Older Adults.

BACKGROUND AND PURPOSE: The pathogenesis of cerebral small vessel disease remains incompletely understood. The relationship between circadian rhythm disturbances and histopathologic measures of cerebral small vessel disease has not been studied. We hypothesized that disrupted circadian rest-activity rhythms would be associated with a higher burden of cerebral small vessel disease pathology. METHODS: We studied 561 community-dwelling older adults (mean age at death, 91.2, 27.4% male) from the Rush Memory and Aging Project. We used actigraphy to quantify several measures of 24-hour rest-activity rhythmicity, including interdaily stability, intradaily variability, and amplitude, and used ordinal logistic regression models to relate these measures to the severity of cerebral arteriolosclerosis, atherosclerosis, macroinfarcts, and microinfarcts, assessed at autopsy. RESULTS: Lower interdaily stability was associated with a higher burden of arteriolosclerosis, higher intradaily variability was associated with a higher burden of atherosclerosis and subcortical infarcts, and lower amplitude was associated with a higher burden of arteriosclerosis, atherosclerosis and subcortical macroinfarcts. Moreover, the associations between interdaily stability and arteriolosclerosis and intradaily variability and subcortical infarcts were independent of cardiovascular risk factors, sleep fragmentation, and medical comorbidities. CONCLUSIONS: Disrupted rest-activity rhythms are associated with a greater burden of cerebral small vessel disease in older adults.

Association of accelerometer-derived sleep measures with lifetime psychiatric diagnoses: A cross-sectional study of 89,205 participants from the UK Biobank.

BACKGROUND: Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the association of accelerometer-derived sleep measures with psychiatric diagnoses and polygenic risk scores in a large community-based cohort. METHODS AND FINDINGS: In this post hoc cross-sectional analysis of the UK Biobank cohort, 10 interpretable sleep measures-bedtime, wake-up time, sleep duration, wake after sleep onset, sleep efficiency, number of awakenings, duration of longest sleep bout, number of naps, and variability in bedtime and sleep duration-were derived from 7-day accelerometry recordings across 89,205 participants (aged 43 to 79, 56% female, 97% self-reported white) taken between 2013 and 2015. These measures were examined for association with lifetime inpatient diagnoses of major depressive disorder, anxiety disorders, bipolar disorder/mania, and schizophrenia spectrum disorders from any time before the date of accelerometry, as well as polygenic risk scores for major depression, bipolar disorder, and schizophrenia. Covariates consisted of age and season at the time of the accelerometry recording, sex, Townsend deprivation index (an indicator of socioeconomic status), and the top 10 genotype principal components. We found that sleep pattern differences were ubiquitous across diagnoses: each diagnosis was associated with a median of 8.5 of the 10 accelerometer-derived sleep measures, with measures of sleep quality (for instance, sleep efficiency) generally more affected than mere sleep duration. Effect sizes were generally small: for instance, the largest magnitude effect size across the 4 diagnoses was ß = -0.11 (95% confidence interval -0.13 to -0.10, p = 3 × 10-56, FDR = 6 × 10-55) for the association between lifetime inpatient major depressive disorder diagnosis and sleep efficiency. Associations largely replicated across ancestries and sexes, and accelerometry-derived measures were concordant with self-reported sleep properties. Limitations include the use of accelerometer-based sleep measurement and the time lag between psychiatric diagnoses and accelerometry. CONCLUSIONS: In this study, we observed that sleep pattern differences are a transdiagnostic feature of individuals with lifetime mental illness, suggesting that they should be considered regardless of diagnosis. Accelerometry provides a scalable way to objectively measure sleep properties in psychiatric clinical research and practice, even across tens of thousands of individuals.

A Novel Composite Biomarker Panel For Detection Of Early Stage Non-small Cell Lung Cancer.

PURPOSE: To investigate a novel composite methodology of using targeted serum microRNAs (micro ribonucleic acid; miRNA) and urine metabolites for the accurate detection of early stage non-small cell lung cancer (NSCLC). METHODS: Consecutively consenting NSCLC patients and matched control subjects were recruited to provide samples of serum for miRNA and/or urine for metabolite analyses. Serum miRNA levels were measured using quantitative real-time reverse-transcription with exogenous control, and the comparative delta cycle threshold (CT) method was used to calculate relative miRNA expression of two targeted miRNAs (miR-21 and miR-223). The concentrations of six targeted urinary metabolites in patients and healthy controls were measured using proton nuclear magnetic resonance (1H NMR) spectroscopy. A composite methodology of using the 35 accruals with both serum and urine biomarkers was then established with binary logistic regression, receiver operating characteristic (ROC) models with or without artificial intelligence (AI). RESULTS: The ROC analysis of miRNA expression yielded a sensitivity of 96.4% and a specificity of 88.2% for the detection of early stage NSCLC, with area under the curve (AUC) = 0.91 (CI 95%: 0.80-1.0). Relative urinary concentrations of 4-methoxyphenylacetic acid (4MPLA) were significantly different between NSCLC and healthy control (p=0.008). The ROC analysis of 4MPLA yielded a sensitivity of 82.1% and a specificity of 88.2%, with AUC = 0.85. The composite process combining miRNA and metabolite expression demonstrated a sensitivity and specificity of nearly 100% and AUC=1. CONCLUSIONS: A highly specific, sensitive and non-invasive detection method for NSCLC was developed. Pending validation, this can potentially improve the early detection and, hence, the treatment and survival outcomes of patients.

Meniscoplasty leads to good mid-term to long-term outcomes for children and adolescents with discoid lateral meniscus.

PURPOSE: To date, there have been limited studies reporting the mid- to long-term outcomes of meniscoplasties for discoid lateral meniscus. The current study aims to evaluate the mid- to long-term outcomes of arthroscopic meniscoplasty for discoid lateral meniscus in children and adolescents. METHODS: In the study, all patients under the age of 21 years who had undergone arthroscopic meniscoplasty with or without meniscal repair or partial meniscectomy for symptomatic lateral discoid meniscus were included. All patients were then followed up for a minimum of 5 years (median 84 months; range 68-110 months). The Lysholm scores and Ikeuchi scores were collected pre-operatively and at final follow-up and were compared. RESULTS: A total of 24 knees were included in the study. The median duration of follow-up was 84.0 months (range 68-110 months). The Lysholm score improved from 53 (range 11-95) pre-operatively to 100.0 (range 60-100) at final follow-up (p < 0.001). Based on the Ikeuchi score pre-operatively, 15 knees were rated as poor (62.5%), 7 knees were rated as fair (29.2%), and 2 knees were rated as good (8.4%). The Ikeuchi score improved significantly at the final follow-up, such that 1 knee was rated as good (4.2%) and 23 knees were rated as excellent (95.8%) (p < 0.001). When analysing the effect of concomitant meniscal repair or partial meniscectomy on the outcomes at final follow-up, there was no apparent difference in the improvement in Lysholm score or Ikeuchi score when comparing between patients who had meniscoplasty alone and patients who had concomitant meniscal repair, as well as when comparing between patients who had meniscoplasty alone and patients who had concomitant partial meniscectomy. CONCLUSION: Meniscoplasty leads to good mid-term to long-term outcomes for children and adolescents with discoid lateral meniscus. Concomitant procedures such as meniscal repair or partial meniscectomy do not improve or worsen the mid- to long-term outcomes in these patients. LEVEL OF EVIDENCE: IV.