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We aimed to report the trajectory of self‐reported outcomes up to 11 years post‐ACLR. We also explored the relationship between hop performance at 1 year and: (i) future self‐reported knee outcomes; and (ii) risk of subsequent knee events. 124 participants (43 women, mean age 31 ± 8 years) were recruited at 1 year following hamstring‐autograft ACLR. Hop performance was assessed with single‐forward and side‐hop tests. Follow‐up was completed at 3 (n = 114), 5 (n = 89) and 11 years (n = 72) post‐ACLR. Self‐reported outcomes were assessed at each follow‐up with the Knee injury Osteoarthritis Outcome Score (KOOS) pain and quality of life (QOL) subscales. Generalized linear mixed models estimated the relationship between hop performance and self‐reported outcomes. Subsequent knee events (new injury/surgery) to either knee were recorded, with the relationship between hop performance and risk of subsequent knee events analyzed with Cox proportional hazards. Self‐reported knee outcomes were stable (mean change < 10 points) across all timepoints but with major within‐sample variability. There was a modest relationship between greater hop performance at 1 year and better future KOOS‐pain (average marginal effect [AME] % improvement with + 1 cm single forward hop = 0.06% [95% CI 0.02–0.10]). A nonlinear spline relationship showed better single‐forward hop performance was associated with better KOOS‐QOL for scores < 108 cm, not present for higher hop scores > 108 cm. There were 21 index and 11 contralateral subsequent knee events. Hop performance was not related to risk of a subsequent knee event (hazard ratio index knee 0.99 [95% CI 0.98–1.02]). In conclusion, self‐reported knee pain and quality of life were generally stable across the 11‐year follow‐up period. Greater hop performance at 1‐year post‐ACLR was related to better self‐reported knee outcomes up to 11‐year follow‐up (of questionable clinical importance), but not associated with the risk of subsequent knee injury/surgery. [ABSTRACT FROM AUTHOR]

This paper explores how research advisory groups can be a vehicle for youth activism. It draws on our experiences with young activists, aged 15–26 years, in India and Brazil, who were advisors on a research project focused on youth livelihoods in cities. These young people played a vital role in supporting youth researchers, identifying research themes and developing engagement and advocacy strategies. Through this paper, we explore how the Youth Expert Group advisory model evolved differently in each location and examine how these were shaped by the context, the 'adult' research team and the youth activists themselves. A critically reflexive response in intergenerational partnership is essential to support youth activists in research activities. [ABSTRACT FROM AUTHOR]

Summary: Background: It is unclear whether the risk of hepatocellular carcinoma (HCC) decreases over time following hepatitis C virus (HCV) eradication. Aim: To determine if patients who have accrued longer time since sustained virologic response (SVR) have a lower risk of HCC than those with less time since SVR Methods: We conducted a retrospective cohort study of all HCV‐infected Veterans Affairs patients who achieved SVR before 1 January 2018 and remained alive without a diagnosis of HCC as of 1 January 2019 (n = 75,965). We ascertained their baseline characteristics as of 1 January 2019 (time zero), including time accrued since SVR and followed them for the subsequent 12 months for incident HCC. We used multivariable Cox proportional hazards regression to determine the association between time since SVR and HCC risk after adjusting for age, race/ethnicity, sex, diabetes, hypertension, body mass index, alcohol use, Charlson Comorbidity Index, Fibrosis‐4 score, HCV genotype, hepatitis B virus co‐infection and HIV co‐infection. Results: 96.0% were male; mean age was 64.6 years. Among those with cirrhosis (n = 19,678, 25.9%), compared to patients who had accrued only ≥1 to 2 years since SVR (HCC incidence 2.71/100 person‐years), those who had accrued >2 to 4 years (2.11/100 person‐years, aHR 0.80, 95% CI 0.63–1.01) and >4 to 6 years (1.65/100 person‐years, aHR 0.61, 95% CI 0.41–0.90) had progressively lower HCC risk. However, HCC risk appeared to plateau for those with >6 years since SVR (1.68/100 person‐years, aHR 0.70, 95% CI 0.46–1.07). Among those without cirrhosis, HCC risk was 0.23–0.27/100 person‐years without a significant association between time since SVR and HCC risk. Conclusions: Among patients with cirrhosis and cured HCV infection, HCC risk declined progressively up to 6 years post‐SVR—although it remained well above thresholds that warrant screening. This suggests that time since SVR can inform HCC surveillance strategies in patients with cured HCV infection and can be incorporated into HCC risk prediction models. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether participants with knee osteoarthritis classified as 'more' or 'less' physically active at baseline differ in characteristics and/or outcomes at baseline and at 3 and 12 months following the commencement of an education and exercise‐therapy program. Methods: Prospective cohort study using the GLA:D® Australia registry. The University of California, Los Angeles Physical Activity Scale (UCLA) participant data dichotomised as 'more' (≥7) or 'less' active (≤6). Groups were compared using chi‐square (obesity [baseline only], comorbidity prevalence, medication consumption, fear of damage from physical activity); and linear mixed model regression (12‐item Injury Osteoarthritis Outcome Score [KOOS‐12], pain [visual analogue scale], health‐related quality of life [QoL] [EQ‐5D‐5L]) statistics, adjusted for age, sex and baseline physical activity at 3 and 12 months. Results: We included 1059 participants (70% female). At baseline, 267 (25%) were classified as 'more' active, increasing to 29% and 30% at 3 and 12 months, respectively. At baseline, compared to the 'less' active group, the 'more' active group had a lower proportion of participants who were obese ('more' = 21% vs. 'less' = 44%), had comorbidities (58% vs. 74%) and consumed medications (71% vs. 85%); lower pain intensity (37 vs. 47); and higher KOOS‐12 (59 vs. 50), and health‐related QoL (0.738 vs. 0.665) scores. When accounting for age, sex and baseline physical activity, improvements seen in knee‐related burden and health‐related QoL were not different between groups at 3 or 12 months. Compared to the 'less' active group, the proportion of participants not consuming medication remained higher in the 'more' active group at 3 ('more' 45% vs. 'less' 28%) and 12 months (43% vs. 32%). Conclusion: 'More' active people with knee osteoarthritis were less likely to be obese, had fewer comorbidities, lower medication consumption, knee‐related burden and pain intensity, and higher health‐related QoL than 'less' active participants at all timepoints. [ABSTRACT FROM AUTHOR]

A functional interplay of bottom‐up and top‐down processing allows an individual to appropriately respond to the dynamic environment around them. These processing modalities can be represented as attractor states using a dynamical systems model of the brain. The transition probability to move from one attractor state to another is dependent on the stability, depth, neuromodulatory tone, and tonic changes in plasticity. However, how does the relationship between these states change in disease states, such as anxiety or depression? We describe bottom‐up and top‐down processing from Marr's computational‐algorithmic‐implementation perspective to understand depressive and anxious disease states. We illustrate examples of bottom‐up processing as basolateral amygdala signaling and projections and top‐down processing as medial prefrontal cortex internal signaling and projections. Understanding these internal processing dynamics can help us better model the multifaceted elements of anxiety and depression. [ABSTRACT FROM AUTHOR]

Patellofemoral joint (PFJ) osteoarthritis is common following anterior cruciate ligament reconstruction (ACLR) and may be linked with altered joint loading. However, little is known about the cross‐sectional and longitudinal relationship between PFJ loading and osteoarthritis post‐ACLR. This study tested if altered PFJ loading is associated with prevalent and worsening early PFJ osteoarthritis post‐ACLR. Forty‐six participants (mean ± 1 SD age 26 ± 5 years) approximately 1‐year post‐ACLR underwent magnetic resonance imaging (MRI) and biomechanical assessment of their reconstructed knee. Trunk and lower‐limb kinematics plus ground reaction forces were recorded during the landing phase of a standardized forward hop. These data were input into a musculoskeletal model to calculate the PFJ contact force. Follow‐up MRI was completed on 32 participants at 5‐years post‐ACLR. Generalized linear models (Poisson regression) assessed the relationship between PFJ loading and prevalent early PFJ osteoarthritis (i.e., presence of a PFJ cartilage lesion at 1‐year post‐ACLR) and worsening PFJ osteoarthritis (i.e., incident/progressive PFJ cartilage lesion between 1‐ and 5‐years post‐ACLR). A lower peak PFJ contact force was associated with prevalent early PFJ osteoarthritis at 1‐year post‐ACLR (n = 14 [30.4%]; prevalence ratio: 1.37; 95% confidence interval [CI]: 1.02–1.85) and a higher risk of worsening PFJ osteoarthritis between 1‐ and 5‐years post‐ACLR (n = 9 [28.1%]; risk ratio: 1.55, 95% CI: 1.13–2.11). Young adults post‐ACLR who exhibited lower PFJ loading during hopping were more likely to have early PFJ osteoarthritis at 1‐year and worsening PFJ osteoarthritis between 1‐ and 5‐years. Clinical interventions aimed at mitigating osteoarthritis progression may be beneficial for those with signs of lower PFJ loading post‐ACLR. [ABSTRACT FROM AUTHOR]

The primary cause for cancer‐related death is metastasis, and although this phenomenon is the hallmark of cancer, it remains poorly understood. Since studies on the underlying mechanisms are still demanding by experimental means prognostic tools based on computer models can be of great value, not only for elucidating metastasis formation but also for assessing the prospective benefits as well as risks of a therapy for patients with advanced cancer. Here, we present an agent‐based model (ABM), describing the complete process of platelet‐assisted extravasation of circulating tumor cells (CTCs) from the chemoattraction of blood platelets by the CTCs up to the embedding of the CTCs in the epithelial tissue by computational means. From the simulation results, we conclude that the ABM produces results in consistency with experimental observations, which opens new perspectives for the development of computer models for predicting the efficacity of drug‐based tumor therapies and assisting precision medicine approaches. [ABSTRACT FROM AUTHOR]

The current cross‐sectional study aimed to extend the literature on childhood adversity by examining the unique associations between potentially traumatic events (PTEs) and a range of mental health concerns, including domain‐specific versus comorbid concerns. Participants were 11,877 preadolescents (47.8% female, 15.0% Black, 20.3% Hispanic/Latinx, Mage = 9.5 years) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study®. The Kiddie Schedule for Affective Disorders and Schizophrenia was used to measure PTEs and caregiver‐ and child‐reported mental health concerns. Adjusted odds ratios (aORs) were used for the outcomes of interest. Overall, PTEs were consistently associated with increased odds of experiencing comorbid posttraumatic stress disorder (PTSD), internalizing disorders, and externalizing disorders, significant AORs = 1.34–4.30, after accounting for children's experiences of other PTEs and polyvictimization. In contrast, PTEs were generally not associated with meeting the criteria for diagnoses within only one domain (i.e., internalizing‐only or externalizing‐only diagnoses). We also found PTEs to be differentially related to the various mental health outcomes. In particular, witnessing domestic violence was consistently associated with children's psychopathology. Other PTEs, such as witnessing community violence, were not associated with children's psychopathology in the final model. Associations between PTEs and mental health concerns did not differ as a function of sex. Overall, the results support the notion that PTEs are associated with comorbid concerns rather than individual disorders. These findings have important implications for the screening of PTEs, continued research on the conceptualization of traumatic stress, and the importance of accounting for comorbidities across mental health domains. [ABSTRACT FROM AUTHOR]

Background: Patellofemoral pain (PFP) affects one-quarter of adolescents, yet there are few evidence-informed recommendations to treat PFP in this population. HAPPi Kneecaps! is a randomised, controlled, participant- and assessor-blind, parallel-group feasibility trial of shoe inserts for adolescents with PFP. The aim of this qualitative study was to explore adolescents' perspectives of participating in HAPPi Kneecaps!. Methods: All 36 adolescents with PFP from the HAPPi Kneecaps! study were invited to participate in semi-structured interviews. We used a descriptive qualitative methodology underpinned by a relativist framework to investigate adolescents' perspectives on participating in the trial. Inductive thematic analysis was used to examine patterns regarding how each adolescent experienced the HAPPi Kneecaps! study within their social, cultural, and historical contexts. Results: 14 out of 36 HAPPi Kneecaps! participants provided consent and participated in interviews (12 females; mean [SD] age 14.9 [2.4] years). Overall, most adolescents responded positively when discussing their experience, such as improvements in their knee pain and satisfaction with how the study was run. Major themes that were generated from the analysis and feedback were: (1) shoe inserts require little effort to use; (2) perceptions of the program were generally positive; (3) participation in the trial could be made easier; (4) warm weather matters; and (5) life happens. Conclusion: Adolescents with PFP who participated in the HAPPi Kneecaps! study found that shoe inserts were easy to wear. Most adolescents experienced an improvement in their symptoms and enhanced participation in sport and exercise. Adolescents with PFP prefer an option for warmer climates (e.g. flip flops or sandals), access to online logbooks, and clinicians who are easily accessible. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000957190. Date registered: 8/07/2019. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses various topics within the issue, including place-based learning, the educational and cultural strategies to support indigenous and minority languages, and language policies.

Cam morphology size and location might affect the severity of reported burden in people with femoroacetabular impingement (FAI) syndrome. We investigated the relationship between cam morphology size (i.e., alpha angle) and self-reported hip/groin burden (i.e., scores for the International Hip Outcome Tool-33 (iHOT-33) and Copenhagen Hip and Groin Outcome Score (HAGOS)), examined separately for the anteroposterior pelvis (AP) and Dunn 45° radiographs in football players with FAI syndrome. In total, 118 (12 women) subelite football (soccer or Australian football) players with FAI syndrome with cam morphology (alpha angle ≥60°) participated. One blinded assessor quantified superior and anterosuperior cam morphology size by measuring alpha angles for the AP and Dunn 45° radiographs, respectively. Linear regression models investigated relationships between alpha angle (continuous independent variable, separately measured for the AP and Dunn 45° radiographs) and iHOT-33 and HAGOS scores (dependent variables). Larger anterosuperior cam morphology (seen on the Dunn 45° radiograph) was associated with lower (i.e., worse) scores for the iHOT-Total, iHOT-Symptoms, iHOT-Job, and iHOT-Social subscales (unadjusted estimate range −0.553 to −0.319 [95% confidence interval −0.900 to −0.037], p = 0.002 to 0.027), but not the iHOT-Sport (p = 0.459) nor any HAGOS scores (p = 0.110 to 0.802). Superior cam morphology size (measured using the AP radiograph) was not associated with any iHOT-33 or HAGOS scores (p = 0.085 to 0.975). Larger anterosuperior cam morphology may be more relevant to pain and symptoms in football players with FAI syndrome than superior cam morphology, warranting investigation of its effects on reported burden and hip disease over time. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to determine the relationship of magnetic resonance imaging (MRI)‐detected features of patellofemoral joint osteoarthritis to pain and functional outcomes. Methods: We sampled 1,099 participants from the 60‐month visit of the Multicenter Osteoarthritis Study (mean ± SD age: 66.8 ± 7.5 years; body mass index: 29.6 ± 4.8; 65% female). We determined the prevalence of MRI‐detected features of patellofemoral joint osteoarthritis (eg, cartilage damage, bone marrow lesions, and osteophytes) and assessed the relationship between these features and knee pain severity, knee pain on stairs, chair stand time, and walking less than 6,000 steps per day. We evaluated the relationship of MRI features to each outcome using logistic and linear regression, adjusting for potential covariates. Results: Participants with cartilage damage in 3‐4 subregions had the highest mean pain severity (22.0/100; 95% confidence interval [CI]: 17.6‐26.4 mm). They also showed higher odds of having at least mild pain on stairs (odds ratio [OR]: 3.3; 95% CI: 1.7‐6.5) and of walking less than 6,000 steps per day (OR: 2.3; 95% CI: 1.1‐4.4) compared with those without cartilage damage. Participants with bone marrow lesions in 3‐4 subregions had higher odds of at least mild pain on stairs than those without (OR: 3.3; 95% CI: 2.2‐5.2). Participants with osteophytes in 3‐4 subregions also had higher odds of walking less than 6,000 steps/day (OR 2.1, 95% CI: 1.3‐3.5, respectively). Conclusion: MRI‐detected features of osteoarthritis of the patellofemoral joint are related to pain and functional performance. This knowledge highlights the need to develop treatments for those with patellofemoral joint osteoarthritis to improve pain and maximize function. [ABSTRACT FROM AUTHOR]

Altered biomechanics are frequently observed following anterior cruciate ligament reconstruction (ACLR). Yet, little is known about knee‐joint loading, particularly in the patellofemoral‐joint, despite patellofemoral‐joint osteoarthritis commonly occurring post‐ACLR. This study compared knee‐joint reaction forces and impulses during the landing phase of a single‐leg forward hop in the reconstructed knee of people 12‐24 months post‐ACLR and uninjured controls. Experimental marker data and ground forces for 66 participants with ACLR (28 ± 6 years, 78 ± 15 kg) and 33 uninjured controls (26 ± 5 years, 70 ± 12 kg) were input into scaled‐generic musculoskeletal models to calculate joint angles, joint moments, muscle forces, and the knee‐joint reaction forces and impulses. The ACLR group exhibited a lower peak knee flexion angle (mean difference: −6°; 95% confidence interval: [−10°, −2°]), internal knee extension moment (−3.63 [−5.29, −1.97] percentage of body weight × participant height (body weight [BW] × HT), external knee adduction moment (‐1.36 [−2.16, −0.56]% BW × HT) and quadriceps force (−2.02 [−2.95, −1.09] BW). The ACLR group also exhibited a lower peak patellofemoral‐joint compressive force (−2.24 [−3.31, −1.18] BW), net tibiofemoral‐joint compressive force (−0.74 [−1.20, 0.28] BW), and medial compartment force (−0.76 [−1.08, −0.44] BW). Finally, only the impulse of the patellofemoral‐joint compressive force was lower in the ACLR group (−0.13 [−0.23, −0.03] body weight‐seconds). Lower compressive forces are evident in the patellofemoral‐ and tibiofemoral‐joints of ACLR knees compared to uninjured controls during a single‐leg forward hop‐landing task. Our findings may have implications for understanding the contributing factors for incidence and progression of knee osteoarthritis after ACLR surgery. [ABSTRACT FROM AUTHOR]

Infrapatellar fat pad (IPFP) morphology and Hoffa‐synovitis may be relevant to the development and progression of post‐traumatic osteoarthritis (OA). We aimed to compare IPFP volume and Hoffa‐synovitis in participants with anterior cruciate ligament reconstruction (ACLR) and uninjured controls, and to determine their association with prevalent and worsening early knee OA features and pain in participants post‐ACLR. We assessed IPFP volume and Hoffa‐synovitis from magnetic resonance imaging (MRI) in 111 participants 1‐year post‐ACLR and 20 uninjured controls. Patellofemoral and tibiofemoral cartilage and bone marrow lesions (BMLs) were assessed from MRIs at 1 and 5 years post‐ACLR, and worsening defined as any longitudinal increase in lesion size/severity. IPFP volume and Hoffa‐synovitis prevalence were compared between groups with analysis of covariance and χ2 tests, respectively. Generalized linear models assessed the relation of IPFP volume and Hoffa‐synovitis to prevalent and worsening features of OA and knee pain (Knee injury and Osteoarthritis Outcome Score—Pain Subscale, Anterior Knee Pain Scale). No significant between‐group differences were observed in IPFP volume (ACLR 34.39 ± 7.29cm3, Control 34.27 ± 7.56cm3) and Hoffa‐synovitis (ACLR 61%, Control 80%). Greater IPFP volume at 1‐year post‐ACLR was associated with greater odds of patellofemoral BMLs at 1‐year (odds ratio [OR] [95% confidence intervals]: 1.104 [1.016, 1.200]) and worsening tibiofemoral cartilage lesions at 5‐year post‐ACLR (OR: 1.234 [1.026, 1.483]). Hoffa‐synovitis at 1‐year post‐ACLR was associated with greater odds of worsening patellofemoral BMLs at 5‐year post‐ACLR (OR: 7.465 [1.291, 43.169]). In conclusion, IPFP volume and Hoffa‐synovitis prevalence are similar between individuals 1‐year post‐ACLR and controls. Greater IPFP volume and Hoffa‐synovitis appear to be associated with the presence and worsening of some early OA features in those post‐ACLR, but not pain. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Vutien et al papers. To view these articles, visit https://doi.org/10.1111/apt.17802 and https://doi.org/10.1111/apt.17818 [ABSTRACT FROM AUTHOR]

Background: Patellofemoral pain (PFP) affects one-third of adolescents and can persist into adulthood, negatively impacting health and quality of life. Foot orthoses are a recommended treatment for adults with PFP, but have not been evaluated in adolescents. The primary objective was to determine the feasibility of conducting a full-scale randomised controlled trial (RCT) evaluating effects of contoured, prefabricated foot orthoses on knee pain severity and patient-perceived global change, compared to flat insoles. The secondary objective was to describe outcomes on a range of patient-reported outcome measures. Methods: We recruited adolescents aged 12–18 years with PFP of ≥2 months duration into a double-blind, randomised, parallel-group feasibility trial. Participants were randomised to receive prefabricated contoured foot orthoses or flat shoe insoles, and followed for 3 months. Participants and outcome assessors were blinded to group allocation. Primary outcomes were feasibility of a full-scale RCT (number of eligible/enrolled volunteers; recruitment rate; adherence with the intervention and logbook completion; adverse effects; success of blinding; drop-out rate), and credibility and expectancy of interventions. Secondary outcomes were patient-reported measures of pain, symptoms, function, quality of life, global rating of change, patient acceptable symptom state, and use of co-interventions. Results: 36 out of 279 (12.9%) volunteers (27 female, mean (SD) age 15 (2) years, body mass 60 (13) kg) were eligible and enrolled, at a recruitment rate of 1.2 participants/week. 17 participants were randomised to receive foot orthoses, and 19 to flat insoles. 15 participants returned logbooks; 7/15 (47%) adhered to the intervention. No serious adverse events were reported. 28% (10/36, 4 pandemic-related) of participants dropped out before 3 months. Blinding was successful. Both groups found the inserts to be credible. Conclusions: Based on a priori criteria for feasibility, findings suggest that a full-scale RCT comparing contoured foot orthoses to flat insoles in adolescents with PFP would not be feasible using the current protocol. Prior to conducting a full-scale RCT, feasibility issues should be addressed, with protocol modifications to facilitate participant retention, logbook completion and shoe insert wear. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000957190. Date registered: 8/07/2019. [ABSTRACT FROM AUTHOR]

Objective: Women diagnosed with cervical glandular intraepithelial neoplasia (CGIN) remain at risk of further pre‐malignant and malignant disease and require rigorous post‐treatment follow‐up. We assess the effectiveness and safety of community cervical sampling follow‐up in women treated for CGIN. Methods: A retrospective study was conducted of women diagnosed with CGIN between April 1, 2013, and March 31, 2019, at Jessop Wing Colposcopy Unit, Sheffield, UK. Results: Of 140 women diagnosed with CGIN, 76 had co‐existing cervical intraepithelial neoplasia (CIN). Cytologists were significantly more likely to report glandular neoplasia in the absence of co‐existing CIN, and high‐grade dyskaryosis in its presence (Ps < 0.0001). Co‐existing CIN was significantly more likely to be present with high or low‐grade compared to normal colposcopy findings (P < 0.0001). The 6‐month test of cure (TOC) was attended by 67% of women (84% within 12 months), and the 18‐month post‐treatment sampling by 52.5% of women (70% within 24 months). Colposcopy recalled 96% of women correctly for the 18‐month sampling, but 20% of women undertaking primary care samples were incorrectly recalled at 3 years instead. Conclusions: When CGIN is diagnosed, two dates for recall should be provided at 6 and 18 months post‐treatment to the Cervical Screening Administration Service and the centralised screening laboratory ensuring the 18‐month post‐treatment sample is correctly appointed, preventing women with HPV‐negative TOC samples being returned to 3‐year recall. Follow‐up of CGIN should be closely audited by the centralised laboratories ensuring women with CGIN are not put at additional risk. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic disease, characterized by the growth of endometrial-like cells outside the uterine cavity. Due to its complex pathophysiology, a totally resolving cure is yet to be found. The aim of this study was to compare the therapeutic efficacy of AZD4547, a novel fibroblast growth factor receptor inhibitor (FGFRI), with a well characterized progestin, etonogestrel (ENG) using a validated in vivo mouse model of endometriosis. Endometriosis was induced by transplanting uterine fragments from donor mice in proestrus into the peritoneal cavity of recipient mice, which then developed into cyst-like lesions. AZD4547 and ENG were administered systemically either from the day of endometriosis induction or 2-weeks post-surgery. After 20 days of treatment, the lesions were harvested; their size and weight were measured and analyzed histologically or by qRT-PCR. Stage of estrous cycle was monitored throughout. Compared to vehicle, AZD4547 (25 mg/kg) was most effective in counteracting lesion growth when treating from day of surgery and 2 weeks after; ENG (0.8 mg/kg) was similarly effective in reducing lesion growth but only when administered from day of surgery. Each downregulated FGFR gene expression (p < 0.05). AZD4547 at all doses and ENG (0.008 mg/kg) caused no disturbance to the estrous cycle. ENG at 0.08 and 0.8 mg/kg was associated with partial or complete estrous cycle disruption and hyperemia of the uteri. AZD4547 and ENG both attenuated endometriotic lesion size, but only AZD4547 did not disrupt the estrous cycle, suggesting that targeting of FGFR is worthy of further investigation as a novel treatment for endometriosis. [ABSTRACT FROM AUTHOR]

Objective: To determine the feasibility of a full‐scale randomized controlled trial (RCT) comparing foot orthoses and footwear to footwear alone in individuals with patellofemoral (PF) osteoarthritis (OA). Methods: This 4‐month, parallel, 2‐arm pilot trial took place in Brisbane, Queensland and Hobart, Tasmania (August 2014 to October 2016). Forty‐six individuals with PF OA were randomized by concealed allocation to foot orthoses plus prescribed footwear (n = 24) or prescribed footwear alone (n = 22). Study feasibility was the primary outcome (e.g., recruitment rate, adherence, adverse events, dropout rate). Secondary outcomes included patient‐reported outcome measures of pain, function, and quality of life. Effect sizes with 95% confidence intervals were calculated at the 4‐month primary end point (standardized mean differences for between‐group effects; standardized response mean for within‐group effects). Results: From 782 volunteers, 47 were eligible (6%), and 46 participated. One participant withdrew (2%), and 1 (2%) was lost to follow‐up. Intervention adherence was high for both groups (9–10 hours of wear per day). No serious adverse events were reported. More than 80% of questionnaires were completed at 4 months. Between‐group effect sizes for patient‐reported outcome measures were typically small, while moderate‐to‐large within‐group response effects were observed in both groups. Conclusion: A full‐scale RCT for PF OA is feasible with modifications to eligibility criteria. However, our observed small between‐group effect sizes, combined with moderate‐to‐large within‐group responses for both interventions, indicate that a full‐scale trial is unlikely to find clinically meaningful differences. Secondary outcomes suggest that both interventions can be recommended for individuals with PF OA. [ABSTRACT FROM AUTHOR]

Introduction: We and collaborators discovered that flickering lights and sound at gamma frequency (40 Hz) reduce Alzheimer’s disease (AD) pathology and alter immune cells and signaling in mice. To determine the feasibility of this intervention in humans we tested the safety, tolerability, and daily adherence to extended audiovisual gamma flicker stimulation. Methods: Ten patients with mild cognitive impairment due to underlying AD received 1-hour daily gamma flicker using audiovisual stimulation for 4 or 8 weeks at home with a delayed start design. Results: Gamma flicker was safe, tolerable, and adherable. Participants’ neural activity entrained to stimulation. Magnetic resonance imaging and cerebral spinal fluid proteomics show preliminary evidence that prolonged flicker affects neural networks and immune factors in the nervous system. Discussion: These findings show that prolonged gamma sensory flicker is safe, tolerable, and feasible with preliminary indications of immune and network effects, supporting further study of gamma stimulation in AD. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to determine whether participant characteristics and clinical assessments could identify radiographic osteoarthritis (OA) in individuals with clinically diagnosed, symptomatic patellofemoral osteoarthritis (PFOA). Methods: Participant characteristics and clinical assessments were obtained from 179 individuals aged 50 years and over with clinically diagnosed symptomatic PFOA, who were enrolled in a randomised trial. Anteroposterior, lateral, and skyline X‐rays were taken of the symptomatic knee. The presence of radiographic PFOA was defined as "no or early PFOA" (Kellgren and Lawrence [KL] grade ≤1 in the PF compartment) or "definite PFOA" (KL grade ≥2). Diagnostic test statistics were applied to ascertain which participant characteristics and clinical assessments could identify the presence of definite radiographic PFOA. Results: A total of 118 participants (66%) had definite radiographic PFOA. Univariate analysis identified that older age (>61 years), female sex, higher body mass index (BMI) (>29 kg/m2), longer pain duration (>2.75 years), higher maximum knee pain during stair ambulation (>47/100 mm), and fewer repeated single step‐ups to pain onset (<21) were associated with the presence of definite radiographic PFOA. Multivariate logistic regression indicated that BMI, pain duration, and repeated single step‐ups to pain onset were independently associated with radiographic PFOA and identified the presence of definite radiographic PFOA with an overall accuracy of 73%. Conclusion: In individuals over 50 years of age with a clinical diagnosis of PFOA, higher BMI, longer pain duration, and fewer repeated single step‐ups to pain onset increased the likelihood of radiographic PFOA. However, overall diagnostic accuracy was modest, suggesting that radiographic PFOA cannot be confidently identified using these tests. [ABSTRACT FROM AUTHOR]

Molecular biomarkers have come to constitute one of the cornerstones of oncological pathology. The method of classification not only directly affects the manner in which patients are diagnosed and treated, but also guides the development of drugs and of artificial intelligence tools. The aim of this article is to organise and update gastrointestinal molecular biomarkers in order to produce an easy‐to‐use guide for routine diagnostics. For this purpose, we have extracted and reorganised the molecular information on epithelial neoplasms included in the 2019 World Health Organization classification of tumours. Digestive system tumours, 5th edn. [ABSTRACT FROM AUTHOR]

Background: Patellofemoral pain (PFP) is a common cause of knee pain in adolescents, but there are limited evidence-based treatment options for this population. Foot orthoses can improve pain and function in adults with PFP, and may be effective for adolescents. The primary aim of this study is to determine the feasibility of conducting a full-scale randomised controlled trial (RCT) evaluating the effects of contoured foot orthoses on knee pain severity and patient-perceived global change, compared to flat shoe insoles, in adolescents with PFP. The secondary aim is to provide an estimate of treatment effects for foot orthoses, compared to flat insoles, in adolescents with PFP. Methods: This randomised, controlled, participant- and assessor-blinded, feasibility trial has two parallel groups. Forty adolescents (aged 12–18 years) with clinical symptoms of PFP will be recruited from Queensland, Australia. Participants will be randomised to receive either prefabricated contoured foot orthoses or flat shoe insoles. Both interventions will be fit by a physiotherapist, and worn for 3 months. Feasibility will be evaluated through assessing willingness of volunteers to enrol, number of eligible participants, recruitment rate, adherence with the study protocol, adverse effects, success of blinding, and drop-out rate. Secondary outcomes will evaluate knee-related pain, symptoms, function, quality of life, global rating of change, patient acceptable symptom state, and use of co-interventions, at 6 weeks and 3 months. Primary outcomes will be reported descriptively, while estimates of standard deviation and between-group differences (with 95% confidence intervals) will be reported for secondary outcomes. Discussion: Findings of this study will inform the feasibility of a full-scale RCT investigating the efficacy of contoured foot orthoses in adolescents with PFP. This full-scale study is necessary to improve the evidence base for management of adolescent PFP, and enhance outcomes for this population. Trial registration: ACTRN12619000957190. [ABSTRACT FROM AUTHOR]

The United Nations Convention on the Rights of the Child has catalysed numerous jurisdictions to introduce new legal provisions to support children's participation rights when child contact is contested. Despite this, children's participation is frequently limited in practice, especially in contexts where children are perceived as vulnerable to a parent's manipulation, even if there are allegations of domestic abuse. While "resist and refusal dynamics" have yet to become mainstream terms in Scottish family law, "manipulation" has become a common concern in cases of contested contact. Drawing on a Scottish empirical study on contested child contact in circumstances of domestic abuse, we interrogate the implications that the concept of manipulation has for children's participation rights. The study involved separate in‐depth interviews with 18 children and their 16 mothers. Findings point to concerns about upholding children's participation rights, particularly in cases where children were depicted as "influenced" or "manipulated." Through our analysis, we disentangle the problems professionals have when concerns about child manipulation and domestic abuse intersect. We argue that, when combined, allegations of manipulation and domestic abuse present a significant and serious risk to children's participation rights. We find the legal construction of the child's views as separate from the parental dispute to have unintended and serious consequences for children's participation rights. We offer ways in which law and practice may evolve to ensure children's participation rights in these contexts are both implemented and upheld. Practitioner's Key Points: The combination of allegations of manipulation and domestic abuse present a significant and serious risk to children's participation rights in contested child contactA legal construction of the child's views as separate to the parental dispute to have unintended and serious consequences for children's participation rightsRadical reform in family law and practice is necessary to make disputes about child contact centered around the child, rather than on parental responsibilities and rights. [ABSTRACT FROM AUTHOR]

Objective: Persistent symptoms and poor quality of life (QoL) are common following anterior cruciate ligament reconstruction (ACLR). We aimed to determine the influence of a combined ACL injury (i.e., concomitant meniscectomy and/or arthroscopic chondral defect at the time of ACLR and/or secondary injury/surgery to ACLR knee) and cartilage defects defined on magnetic resonance imaging (MRI), bone marrow lesions (BMLs), and meniscal lesions on patient-reported outcomes 1 to 5 years after ACLR.Methods: A total of 80 participants (50 men; mean ± SD age 32 ± 14 years) completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) questionnaires as well as a 3T MRI assessment at 1 and 5 years after ACLR. Median patient-reported outcome scores were compared between isolated and combined ACL injuries and with published normative values. Using multivariate regression, we evaluated the association between compartment-specific MRI cartilage, BMLs, and meniscal lesions and patient-reported outcomes at 1 and 5 years.Results: Individuals with a combined injury had significantly worse scores in the KOOS subscale of function in sport and recreation (KOOS sport/rec) and in the IKDC questionnaire at 1 year, and worse scores in the KOOS subscales of pain (KOOS pain), symptoms (KOOS symptoms), and QoL (KOOS QoL) and in the IKDC questionnaire at 5 years compared to those with an isolated injury. Although no feature on MRI was associated with patient-reported outcomes cross-sectionally at 1 year, patellofemoral cartilage defects at 1 year were significantly associated with worse 5-year KOOS symptoms (β = -9.79, 95% confidence interval [95% CI] -16.67, -2.91), KOOS sport/rec (β = -7.94, 95% CI -15.27, -0.61), KOOS QoL (β = -8.29, 95% CI -15.28, -1.29), and IKDC (β = -4.79, 95% CI -9.34, -0.24) scores. Patellofemoral cartilage defects at 5 years were also significantly associated with worse 5-year KOOS symptoms (β = -6.86, 95% CI -13.49, -0.24) and KOOS QoL (β = -11.71, 95% CI -19.08, -4.33) scores.Conclusion: Combined injury and patellofemoral cartilage defects shown on MRI are associated with poorer long-term outcomes. Clinicians should be vigilant and aware of individuals with these injuries, as such individuals may benefit from targeted interventions to improve QoL and optimize symptoms. [ABSTRACT FROM AUTHOR]

For some rare tumours, distinctive driver mutations have been identified; for example, the characteristic I MALAT1 i - I GLI1 i fusion gene in gastroblastoma and I EWSR1 i fusions in gastrointestinal clear cell sarcoma and malignant gastrointestinal neuroectodermal tumour. The recently renamed goblet cell adenocarcinoma (formerly called goblet cell carcinoid/carcinoma) of the appendix is a prime example of a tumour whose biological potential and histological characteristics have been better described, resulting in improvements in the pathological approach to these tumours. As highlighted above, precursor lesions including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are now classified into two tiers of dysplasia, based on the highest grade of dysplasia detected, rather than the three-tier system used in the last edition of the WHO classification. A number of other genetic tumour predisposition syndromes that confer a raised risk of various gastrointestinal tumours are also described, including Li-Fraumeni syndrome, hereditary haemorrhagic telangiectasia, syndromes associated with gastroenteropancreatic NETs and multilocus inherited neoplasia alleles syndrome. [Extracted from the article]

Objective: To determine the association of self‐selected walking step rate with worsening of cartilage damage in the patellofemoral (PF) joint and tibiofemoral (TF) joint compartments at a 2‐year follow‐up visit. Methods: The Multicenter Osteoarthritis Study (MOST) is a prospective cohort of men and women with or at risk of knee osteoarthritis. Self‐selected step rate was measured using an instrumented GAITRite walkway (CIR Systems) at the 60‐month visit. Cartilage damage was semiquantitatively graded on magnetic resonance images at the 60‐ and 84‐month visits in the medial and lateral PF and TF compartments. Step rate was divided into quartiles, and logistic regression was used to determine the association of step rate with the risk of worsening cartilage damage in men and women separately. Analyses were adjusted for age, body mass index, and knee injury/surgery. Results: A total of 1,089 participants were included. Mean ± SD age was 66.9 ± 7.5 years, mean ± SD body mass index was 29.6 ± 4.7 kg/m2, and 62.3% of the participants were women. Women with the lowest step rate had increased risk of lateral PF (risk ratio [RR] 2.1 [95% confidence interval (95% CI) 1.1–3.8]) and TF (RR 1.8 [95% CI 1.1–2.9]) cartilage damage worsening 2 years later compared to those with the highest step rate. Men with the lowest step rate had increased risk of medial TF cartilage damage worsening 2 years later (RR 2.1 [95% CI 1.1–3.9]). Conclusion: Lower step rate was associated with increased risk of cartilage damage worsening in the lateral PF and TF compartments in women and worsening medial TF joint damage in men. Future research is necessary to understand the influence of step rate manipulation on joint biomechanics in women and men. [ABSTRACT FROM AUTHOR]

Social connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an "innate need," it is hypothesized that evolutionarily conserved neural systems underlie the maintenance of social connections: alerting the individual to their absence and coordinating effector mechanisms to restore social contact. This is reminiscent of a homeostatic system designed to maintain social connection. Here, we explore the identity of neural systems regulating "social homeostasis." We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry. We reason that uncovering the identity of these circuits/mechanisms will facilitate our understanding of how loneliness perpetuates long‐term disease states, which we speculate may result from sustained recruitment of social homeostatic circuits. [ABSTRACT FROM AUTHOR]

Objective: To describe the prevalence of radiographic features of patellofemoral (PF) osteoarthritis (OA) in adults with persistent PF pain, to describe the prevalence of magnetic resonance imaging (MRI)-defined PF OA and compare it to that in age- and sex-matched controls, and to explore the prevalence of radiographic and MRI-defined PF OA across age, sex, and body mass index (BMI) groups.Methods: This cross-sectional study included 84 individuals with PF pain ≥3 months duration and 26 age- and sex-matched controls. In participants with PF pain, posteroanterior, lateral, and skyline radiographs were obtained. Radiographic OA features were scored using Kellgren/Lawrence (K/L) criteria and a radiographic atlas, with K/L grade ≥2 defined as OA, and K/L grade 1 as early OA. Both groups underwent 3.0 Tesla MRI scans, scored using the MRI Osteoarthritis Knee Score criteria. Compartmental prevalence of MRI OA features was based on cartilage lesions, bone marrow lesions (BMLs), and osteophytes.Results: Overall, 20 participants (24%) with PF pain had radiographic PF OA (K/L grade ≥2), and 36 participants (43%) had early PF OA (K/L grade 1). MRI-defined PF OA was more prevalent in participants with PF pain (16-29%) than in controls (4-12%), irrespective of how PF OA was defined. Within the PF pain group, the prevalence of PF OA on radiographs and MRI was greater in participants who were older or female or who had a higher BMI.Conclusion: Features of radiographic and MRI-defined PF OA were evident in 20-30% of adults ages 26-50 years with persistent PF pain, with greater prevalence observed in those who were older, or female, or who had a higher BMI. MRI-defined PF OA was more prevalent in individuals with PF pain than in pain-free controls, especially when defined as a full-thickness cartilage lesion with BML. [ABSTRACT FROM AUTHOR]

Patellofemoral (PF) osteoarthritis (OA) is a prevalent and clinically important knee OA subgroup. Malalignment may be an important risk factor for PF OA. However, little is known about alignment in PF OA, particularly in an upright, weightbearing environment. Using a vertically‐oriented open‐bore MR scanner, we evaluated 3D knee alignment in 15 PF OA cases and 15 individually matched asymptomatic controls. We imaged one knee per participant while they stood two‐legged at four flexion angles (0°, 15°, 30°, 45°), and also while they stood one‐legged at 30° knee flexion. We calculated 3D patellofemoral and tibiofemoral alignment. Using mixed effects models, four of the five patellofemoral measures differed by group. For key measures, PF OA patellae were 6.6° [95%CI 5.0, 8.2] more laterally tilted, 2.4 mm [1.3, 3.5] more laterally translated, and at least 3.7 mm [0.2, 7.2] more proximally translated compared to controls (more with knees flexed). Alignment did not differ between two‐legged stance and one‐legged stance in either group. Statement of Clinical Significance: Our study demonstrated significant and clinically relevant differences in alignment between PF OA cases and controls in upright standing and squatting positions. Our findings were similar to those in previous studies of PF OA using traditional MR scanners in supine positions, supporting the clinical usefulness of existing methods aimed at identifying individuals who may benefit from interventions designed to correct malalignment. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. 9999:1–9, 2019. [ABSTRACT FROM AUTHOR]

ABSTRACT: This study quantified the contributions by muscular, gravitational and inertial forces to the ground reaction force (GRF) and external knee adduction moment (EKAM) for knee osteoarthritis (OA) patients and controls walking at similar speeds. Gait data for 39 varus mal‐aligned medial knee OA patients and 15 controls were input into musculoskeletal models to calculate the contributions of individual muscles and gravity to the fore‐aft (progression), vertical (support), and mediolateral (balance) GRF, and the EKAM. The temporal patterns of contributions to GRF and EKAM were similar between the groups. Magnitude differences in GRF contributions were small but some reached significance. Peak GRF contributions were lower in patients except hamstrings in early‐stance progression (p < 0.001) and gastrocnemius in late‐stance progression (p < 0.001). Both EKAM peaks were higher in patients, due mainly to greater adduction contribution from gravity (p < 0.001) at the first peak, and lower abduction contributions from soleus (p < 0.001) and gastrocnemius (p < 0.001) at the second peak. Gluteus medius contributed most to EKAM in both groups, but was higher in patients during mid‐stance only (p < 0.001). Differences in GRF contributions were attributed to altered quadriceps‐hamstrings action as well as compensatory adaptation of the ankle plantarflexors to reduced gluteus medius action. The large effect of varus mal‐alignment on the frontal‐plane moment arms of the gravity, soleus, and gastrocnemius GRF contributions about the knee explained greater patient EKAM. Our results shed further light on how the EKAM contributes to altered knee‐joint loads in OA and why some interventions may affect different portions of the EKAM waveform. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2157–2166, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT: The purpose of this study was to compare hip and knee biomechanics during walking in individuals with isolated tibiofemoral osteoarthritis (TFOA), combined TFOA and patellofemoral osteoarthritis (PFOA), and those without knee osteoarthritis (OA), and to compare patient‐reported symptoms and function in individuals with isolated TFOA and those with combined TFOA and PFOA. Participants with and without knee OA were assessed and categorized into (i) no OA, (ii) isolated TFOA, and (iii) combined TFOA and PFOA, based on Kellgren and Lawrence diagnostic criteria. Quantitative motion analyses were conducted during walking, and hip and knee kinematics, and external moments were calculated. Peak values in the sagittal and frontal planes during stance phase were computed. Patient‐reported symptoms and function data were obtained using the Western Ontario McMaster Universities Arthritis Index. Multivariate analyses of variance were conducted to compare between‐group differences in gait and patient‐reported symptoms and function data. The results showed no statistically significant differences in hip and knee kinematics and external moments between the three groups. Relative to those with isolated TFOA, individuals with combined TFOA and PFOA had greater pain (mean difference [95%CI]: 1.5 [0.05–3.1]), stiffness (0.8 [0.02–1.5]), and poorer function (5.4 [0.2–10.7]). In conclusion, the combined TFOA and PFOA radiographic disease pattern is associated with worse pain and function compared to the isolated TFOA disease pattern. The results of the present study provide no indications that treatments designed to change walking biomechanics should differ between individuals with isolated TFOA and those with combined TFOA and PFOA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1666–1672, 2018. [ABSTRACT FROM AUTHOR]

Background: A timely return to competitive sport is a primary goal of anterior cruciate ligament reconstruction (ACLR). It is not known whether an accelerated return to sport increases the risk of early-onset knee osteoarthritis (KOA).Objective: To determine whether an accelerated return to sport post-ACLR (ie, <10 months) is associated with increased odds of early KOA features on magnetic resonance imaging (MRI) 1 year after surgery and to evaluate the relationship between an accelerated return to sport and early KOA features stratified by type of ACL injury (isolated or concurrent chondral/meniscal injury) and lower limb function (good or poor).Design: Cross-sectional study.Setting: Private radiology clinic and university laboratory.Participants: A total of 111 participants (71 male; mean age 30 ± 8 years) 1-year post-ACLR.Methods: Participants completed a self-report questionnaire regarding postoperative return-to-sport data (specific sport, postoperative month first returned), and isotropic 3-T MRI scans were obtained.Outcome Measures: Early KOA features (bone marrow, cartilage and meniscal lesions, and osteophytes) assessed with the MRI OA Knee Score. Logistic regression analyses evaluated the odds of early KOA features with an accelerated return to sport (<10 months post-ACLR versus ≥10 months or no return to sport) in the total cohort and stratified by type of ACL injury and lower limb function.Results: Forty-six (41%) participants returned to competitive sport <10 months post-ACLR. An early return to sport was associated with significantly increased odds of bone marrow lesions (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3-6.0) but not cartilage (OR 1.2, 95% CI 0.5-2.6) or meniscal lesions (OR 0.8, 95% CI 0.4-1.8) or osteophytes (OR 0.6, 95% CI 0.3-1.4). In those with poor lower limb function, early return to sport exacerbated the odds of bone marrow lesions (OR 4.6, 95% CI 1.6-13.5), whereas stratified analyses for type of ACL injury did not reach statistical significance.Conclusion: An accelerated return to sport, particularly in the presence of poor lower limb function, may be implicated in posttraumatic KOA development.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

Purpose: To develop methods for evaluating 3D patellofemoral and tibiofemoral alignment in vertical open-bore magnetic resonance (MR) scanners, with participants upright and fully weight-bearing; and to evaluate the repeatability of these methods in individuals with patellofemoral osteoarthritis (OA) and in asymptomatic knees.Materials and Methods: Our methods extend previously validated, reliable methods for evaluating alignment into an upright MR environment. In 10 participants with early patellofemoral OA and 10 with asymptomatic knees, we acquired sagittal T1 -weighted turbo spin echo images in a 3T scanner to create accurate participant-specific 3D anatomical surface models. In a vertical open-bore 0.5T MR scanner, we obtained lower-resolution sagittal gradient echo images to capture bony position and orientation data. Participants were scanned in a position of squatting with the knees flexed 30°, three separate times to evaluate repeatability. Bone segmentation was performed manually, surface models were registered to data from the 0.5T scanner, and 3D patellofemoral and tibiofemoral alignment was calculated in all six degrees of freedom (three rotations and three translations).Results: Intraclass correlation coefficients (ICCs) were ≥0.94, with the exception of patellar spin (0.79). Standard errors of measure (SEM) were <2° rotation and <0.9 mm translation. Repeatability remained adequate when stratified by group, with the exception of patellar spin (ICC 0.57 for asymptomatic knees vs. 0.91 for OA knees).Conclusion: We demonstrate methods for evaluating 3D alignment in upright fully weight-bearing participant positions in a vertical open-bore MR scanner. With the exception of patellar spin, repeatability was good to excellent.Level Of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:841-847. [ABSTRACT FROM AUTHOR]

Background: Age-related changes in midfoot mobility have the potential to influence success with foot orthoses intervention in people with patellofemoral pain (PFP). The aim of this study was to determine whether older people with PFP demonstrate less foot mobility than younger adults with PFP. Methods: One hundred ninety four participants (113 (58%) women, age 32 ± 7 years, BMI 25 ± 4.9 kg/m²) with PFP (≥ 6 weeks duration) were included, with foot mobility quantified using reliable and valid methods. K-means cluster analysis classified participants into three homogenous groups based on age. After cluster formation, univariate analyses of co-variance (covariates: sex, weight) were used to compare midfoot height mobility, midfoot width mobility, and foot mobility magnitude between age groups (significance level 0.05). Results: Cluster analysis revealed three distinct age groups: 18--29 years (n = 70); 30--39 years (n = 101); and 40--50 years (n = 23). There was a significant main effect for age for midfoot height mobility (p < 0.001) and foot mobility magnitude (p = 0.006). Post-hoc analyses revealed that midfoot height mobility differed across all three groups (moderate to large effect sizes), and that foot mobility magnitude was significantly less in those aged 40--50 years compared to those aged 18--25 years (moderate effect size). There were no significant main effects for age for midfoot width mobility (p > 0.05). Conclusion: Individuals with PFP aged 40--50 years have less foot mobility than younger adults with PFP. These findings may have implications for evaluation and treatment of older individuals with PFP. [ABSTRACT FROM AUTHOR]

Objective: Patellofemoral (PF) joint osteoarthritis (OA) is common, yet little is known about how this condition influences lower-extremity biomechanical function. This study compared pelvis and lower-extremity kinematics in people with and without PF joint OA.Methods: Sixty-nine participants (64% women, mean ± SD age 56 ± 10 years) with anterior knee pain aggravated by PF joint-loaded activities (e.g., stair ambulation, rising from sitting, or squatting) and radiographic lateral PF joint OA on skyline radiographs were compared with 18 controls (78% women, mean ± SD age 53 ± 7 years) with no lower-extremity pain or radiographic OA. Knee Injury and Osteoarthritis Outcome Score (KOOS) data were collected from participants with PF joint OA. Quantitative gait analyses were conducted during overground walking at a self-selected speed. Pelvis and lower-extremity kinematics were calculated across the stance phase. Data were statistically analyzed using analyses of covariance, with age and sex as covariates (P < 0.05).Results: Participants with PF joint OA reported a mean ± SD KOOS pain subscale score of 65 ± 15, KOOS symptoms subscale score of 63 ± 16, KOOS activities of daily living subscale score of 73 ± 13, KOOS sports/recreation subscale score of 45 ± 23, and KOOS quality of life subscale score of 43 ± 16. Participants with PF joint OA walked with greater anterior pelvic tilt throughout the stance phase, as well as greater lateral pelvic tilt (i.e., pelvis lower on the contralateral side), greater hip adduction, and lower hip extension during the late stance phase. No differences in knee and ankle joint angles were observed between groups.Conclusion: People with PF joint OA walk with altered pelvic and hip movement patterns compared with aged-matched controls. Restoring normal movement patterns during walking in people with PF joint OA may be warranted to help alleviate symptoms. [ABSTRACT FROM AUTHOR]

Histological transformation ( HT) of follicular lymphoma ( FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy ( RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% ( n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT. 48% (12/25) of patients who received fludarabine developed HT. The estimated 10-year risk of HT in the fludarabine and non-fludarabine groups was 67% and 26% respectively ( P = 0·015). Only prior fludarabine was significantly associated with predicting the risk of HT after RIT. 8% (9/115) of patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia ( tMDS/ AML) at a median of 41·4 months (range, 5-89). The estimated 10-year risk of tMDS/ AML in non-fludarabine treated patients ( n = 90) versus fludarabine treated ( n = 25) was 13% and 29%, respectively. The estimated overall risk of FL undergoing HT at 10 years without fludarabine exposure appears similar to patients reported in the literature that have not received RIT. Patients with prior purine-analogue therapy are at significantly higher risk of HT. [ABSTRACT FROM AUTHOR]

Background: Patellofemoral joint osteoarthritis is a common condition, yet information regarding conservative management is lacking. Foot orthoses are an effective intervention for improving pain and function in younger individuals with patellofemoral pain and may be effective in those with patellofemoral osteoarthritis. This pilot study will seek to establish the feasibility of a phase III randomised controlled trial to investigate whether foot orthoses worn in prescribed motion controlled footwear are superior to prescribed motion control footwear alone in the management of patellofemoral osteoarthritis. Methods/design: This phase II pilot clinical trial is designed as a randomized, single-blind, parallel group, two arm, superiority trial. The trial will recruit 44 participants from Queensland and Tasmania, Australia. Volunteers aged 40 years and over must have clinical symptoms and radiographic evidence of patellofemoral osteoarthritis to be eligible for inclusion. Those eligible will be randomized to receive either foot orthoses and prescribed motion control shoes, or prescribed motion control shoes alone, to be worn for a period of 4 months. The feasibility of a phase III clinical trial will be evaluated by assessing factors such as recruitment rate, number of eligible participants, participant compliance with the study protocol, adverse events, and drop-out rate. A secondary aim of the study will be to determine completion rates and calculate effect sizes for patient reported outcome measures such as knee-related symptoms, function, quality of life, kinesiophobia, self-efficacy, general and mental health, and physical activity at 2 and 4 months. Primary outcomes will be reported descriptively while effect sizes and 95% confidence intervals will be calculated for the secondary outcome measures. Data will be analysed using an intention-to-treat principle. Discussion: The results of this pilot trial will help determine the feasibility of a phase III clinical trial investigating whether foot orthoses plus motion control footwear are superior to motion control footwear alone in individuals with patellofemoral osteoarthritis. A Phase III clinical trial will help guide footwear and foot orthoses recommendations in the clinical management of this disorder. [ABSTRACT FROM AUTHOR]

ABSTRACT This study quantified the contributions by muscles, gravity, and inertia to the tibiofemoral compartment forces in the symptomatic (SYM) and asymptomatic (ASYM) limbs of varus mal-aligned medial knee osteoarthritis (OA) patients, and compared the results with healthy controls (CON). Muscle forces and tibiofemoral compartment loads were calculated using gait data from 39 OA patients and 15 controls aged 49 ± 7 years. Patients exhibited lower knee flexion angle, higher hip abduction, and knee adduction angles, lower internal knee flexion torque but higher external knee adduction moment. Muscle forces were highest in CON except hamstrings, which was highest in SYM. ASYM muscle forces were lowest for biceps femoris short head and gastrocnemius but otherwise intermediate between SYM and CON. In all subjects, vasti, hamstrings, gastrocnemius, soleus, gluteus medius, gluteus maximus, and gravity were the largest contributors to medial compartment force (MCF). Inertial contributions were negligible. Highest MCF was found in SYM throughout stance. Small increases in contributions from hamstrings, gluteus maximus, gastrocnemius, and gravity at the first peak; soleus and rectus femoris at the second peak; and soleus, gluteus maximus, gluteus medius, and gravity during mid-stance summed to produce significantly higher total MCF. Compared to CON, the ASYM limb exhibited similar peak MCF but higher mid-stance MCF. In patients, diminished non-knee-spanning muscle forces did not produce correspondingly diminished MCF contributions due to the influence of mal-alignment. Our findings emphasize consideration of muscle function, lower-limb alignment, and mid-stance loads in developing interventions for OA, and inclusion of the asymptomatic limb in clinical assessments. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:321-330, 2017. [ABSTRACT FROM AUTHOR]

Objective: We conducted a systematic review to evaluate the associations of knee alignment or trochlear morphology (measured on imaging) with presence, severity, onset, and/or progression of patellofemoral osteoarthritis (PFOA).Methods: We prospectively registered our protocol with PROSPERO (International prospective register of systematic reviews) and followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to report this review. We searched 10 electronic databases, screened citing articles, and reviewed reference lists. We extracted data and evaluated methodologic quality. Due to study design heterogeneity, we used a best-evidence synthesis to summarize the evidence.Results: We included 16 publications (2,892 participants, 66% women) after removing 4 papers that did not meet our threshold for methodologic quality. There were 11 cross-sectional and 5 longitudinal papers. The target population was knee OA in 11 studies, PFOA in 2 studies, and other knee conditions in 3 studies. Alignment or morphology was measured using radiographs in 8 studies, magnetic resonance imaging in 7 studies, and computed tomography in 2 papers. Limitations include substantial heterogeneity in samples and methods, short followup times in longitudinal studies, and a small number of studies that specifically recruited participants with PFOA.Conclusion: There is strong evidence that PFOA is associated with both trochlear morphology and frontal plane knee alignment, while evidence is limited but consistent in the sagittal and axial planes. These findings suggest that alignment should be evaluated clinically in individuals with PFOA. Clinical interventions targeting knee alignment warrant further investigation. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the presence of magnetic resonance imaging (MRI) osteoarthritis (OA) features in the patellofemoral or tibiofemoral joint (i.e., bone marrow lesions, cartilage lesions, and osteophytes) and/or functional impairments, 1 year following anterior cruciate ligament reconstruction (ACLR), can predict Knee Injury and Osteoarthritis Outcome Score (KOOS) at 3 years.Methods: A total of 93 participants (56 [60%] men, mean ± SD age 29 ± 9 years) who had undergone MRI examination and functional testing at 1-year post-ACLR, completed the KOOS at 3 years postsurgery. Multivariate regression models evaluated the prognostic capacity of compartment-specific osteochondral OA features, scored using the MRI Osteoarthritis Knee Score, and functional performance (hop for distance, 1-leg rise), to predict outcome on 4 KOOS subscales (pain, symptoms, sport/recreation, and quality of life [QOL]).Results: Presence of patellofemoral cartilage lesions 1-year post-ACLR predicted worse score on all KOOS subscales at 3 years (P ≤ 0.01). Regression coefficients (B) were -5.1 (95% confidence interval [95% CI] -9.1, -1.2) for symptoms, -4.0 (95% CI -6.7, -1.4) for pain, -6.7 (95% CI -11.0, -2.4) for sport/recreation, and -8.6 (95% CI -15.1, -2.1) for QOL. No significant associations were found between tibiofemoral MRI features and knee symptoms. Poorer performance on the 1-leg-rise test predicted worse KOOS-QOL (B -6.5 [95% CI -12.4, -0.5], P = 0.03).Conclusion: The presence of a patellofemoral articular cartilage lesion and lower 1-leg-rise performance at 1 year postsurgery are prognostic for poorer 3-year outcome following ACLR. Particular attention to patellofemoral compartment lesions and functional capacity is warranted during postoperative rehabilitation programs, as these features represent potential targets for therapy aimed at minimizing symptomatic disease progression in these young adults. [ABSTRACT FROM AUTHOR]

Objective: To evaluate single-leg squat performance 1-2 years after arthroscopy for intra-articular hip pathology compared with control subjects and the nonsurgical limb, and to investigate whether single-leg squat performance on the operated limb was associated with hip muscle strength.Design: Cross-sectional study.Setting: Private physiotherapy clinic and university laboratory.Participants: Thirty-four participants (17 women, 36.7 ± 12.6 years) 1-2 years after hip arthroscopy and 34 gender-matched control subjects (17 women, 33.1 ± 11.9 years).Methods: Participants performed single-leg squats using a standardized testing procedure. Squat performance was captured using video. Video footage was uploaded and reformatted for analyses. Hip muscle strength was measured with handheld dynamometry using reliable methods.Outcome Measures: Frontal plane pelvic obliquity, hip adduction, and knee valgus were measured. Repeated measures analysis of variance evaluated between-group differences, with limb as a within-subjects factor (surgical versus nonsurgical) and gender as a between-subjects factor (P < .05).Results: The hip arthroscopy group demonstrated significantly greater apparent hip adduction (mean difference 2.7°, 95% confidence interval [CI] 0.7°-4.8°) and apparent knee valgus (4.0°, 95% CI 1.0°-7.1°) at peak squat depth compared with control subjects. The operated limb also demonstrated significantly greater pelvic obliquity during single-leg stance compared with the nonsurgical limb (1.2°, 95% CI 0.1°-2.3°). Women had significantly greater apparent hip adduction (standing 1.6°, 95% CI 0.5°-2.6°; peak squat depth 2.4°, 95% CI 0.3°-4.4°) and apparent knee valgus (standing 3.3°, 95% CI 1.8°-4.7°; peak squat depth 3.1°, 95% CI 0°-6.1°). Significant positive correlations were found between frontal plane angles and hip flexor and extensor peak torque (P > .05).Conclusion: One to 2 years after hip arthroscopy, deficits in single-leg squat performance exist that have the potential to increase hip joint impingement and perpetuate postoperative symptoms. Rehabilitation after hip arthroscopy should target retraining in functional single-leg positions. [ABSTRACT FROM AUTHOR]

Background: In the absence of active blood donation screening, dengue viruses (DENV) have been implicated in only a limited number of transfusion transmissions worldwide. This study attempted to identify if blood from donors testing negative by an NS1-antigen (Ag) enzyme-linked immunosorbent assay (ELISA) but confirmed positive for DENV RNA caused DENV-related disease in recipients during the epidemic years of 2010 to 2012 in Puerto Rico.Study Design and Methods: Donation aliquots testing negative by an investigational NS1-Ag ELISA were stored frozen and retested retrospectively using a research transcription-mediated amplification assay (TMA) detecting DENV RNA. All RNA-reactive donations were subject to confirmatory RNA and antibody testing. Recipient tracing was conducted for all components manufactured from TMA-reactive components. Medical chart review, recipient interview, and follow-up sampling occurred for 42 recipients transfused with TMA-reactive components.Results: Six of 42 recipients developed new-onset fever in the 2 weeks posttransfusion; three (50%) received RNA confirmed-positive, NS1-Ag-negative red blood cell (RBC) units. One recipient of a high-titer unit (7 × 10(7) DENV-4 RNA copies/mL) developed severe dengue, and a second recipient had only fever recorded but had a negative sepsis work-up. New fever attributable to DENV infection in a third recipient was confounded by fever potentially attributable to posttransfusion sepsis.Conclusions: In our retrospective study, NS1-Ag detected 20% of all RNA confirmed-positive donations demonstrating limitations of NS1-Ag ELISA for blood donation screening. We identified one recipient with a clinical syndrome compatible with severe dengue who had received an NS1-Ag-negative but RNA confirmed-positive RBC unit. This investigation illustrates the difficulty in confirming transfusion transmission in dengue-endemic areas among severely ill transfusion recipients. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the attitudes and practices of Australian general practitioners (GPs) regarding infant gastro-oesophageal reflux disease (GORD) diagnosis and management.Methods: A national cross-sectional survey, involving a random sample of currently practising Australian GPs (n = 2319) was undertaken between July and September 2011. GPs attitudes and management of infant GORD were surveyed via an online and paper-based 41-item questionnaire.Results: In total, 400 responses were analysed (17.24% response rate). The majority of GPs employed empirical trials of acid-suppression medication and/or lifestyle modifications to diagnose infant GORD. GPs frequently recommended dietary modification despite the belief that they were only moderately effective at best. In addition, GPs frequently prescribed acid-suppression medication, despite concerns regarding their safety in the infant population. Other GP concerns included the lack of clinical guidelines and education for GPs about infant GORD, as well as the level of evidence available for the safety and efficacy of diagnostic tests and treatments.Conclusion: Despite the important role Australian GPs play in the diagnosis and management of infant GORD, high-level evidence-based guidelines for GPs are lacking. Consequently, GPs engage in diagnostic and management practices despite their concerns regarding the safety and effectiveness. [ABSTRACT FROM AUTHOR]

The article focuses on translation process of magnetic resonance elastography (MRE) and key science and technology, application to chronic liver diseases and key clinical studies. It mentions U.S. Food and Drug Administration (FDA) approval process, and its influence on current and future medical practice and glycogen storage. It also mentions use of predicate devices for the approval of medical devices, and the 510(k) mechanism.

Objective To determine the prevalence and factors associated with knee osteoarthritis (OA) defined by magnetic resonance imaging (MRI) and specific OA features on MRI 1 year after anterior cruciate ligament reconstruction (ACLR). Methods Isotropic 3.0T MRI scans were obtained for 111 participants (71 men; mean ± SD age 30 ± 8 years) 1 year after ACLR as well as for 20 age-, sex-, and activity level-matched uninjured controls. The MRI OA Knee Score was used to score specific OA features. MRI-defined tibiofemoral and patellofemoral OA was evaluated based on published criteria. Logistic regression identified factors associated with MRI-defined OA and specific OA features after ACLR. Results Following ACLR, medial and lateral tibiofemoral OA on MRI was observed in 7 participants (6%) and 12 participants (11%), respectively, while 19 participants (17%) had patellofemoral OA on MRI. The femoral trochlea was the region most affected by bone marrow lesions (19% of participants), cartilage lesions (31% of participants), and osteophytes (37% of participants). Meniscectomy at the time of ACLR (odds ratio 6.8 [95% confidence interval 2.0-23.3]) and body mass index (BMI) >25 kg/m2 (odds ratio 3.0 [95% confidence interval 1.3-6.9]) predicted MRI-defined tibiofemoral OA and osteophytes, respectively. Men had higher odds of patellofemoral osteophytes (odds ratio 6.3 [95% confidence interval 2.4-16.2]). No uninjured controls had tibiofemoral or patellofemoral OA on MRI, and specific OA features were uncommon. Conclusion OA 1 year following ACLR was more common than previously recognized, while being absent in uninjured control knees. The patellofemoral compartment seems to be at particular risk for early OA after ACLR, especially in men. The association with meniscectomy and BMI demonstrates the construct validity of MRI criteria. [ABSTRACT FROM AUTHOR]