Test-Retest Repeatability of Patlak Slopes versus Standardized Uptake Values for Hypermetabolic Lesions and Normal Organs in an Oncologic PET/CT Population.

PURPOSE: We aimed to determine the test-retest repeatability of quantitative metrics based on the Patlak slope (PS) versus the standardized uptake value (SUV) among lesions and normal organs on oncologic [18F]FDG-PET/CT. PROCEDURES: This prospective, single-center study enrolled adults undergoing standard-of-care oncologic [18F]FDG-PET/CTs. Early (35-50 min post-injection) and late (75-90 min post-injection) SUV and PS images were reconstructed from dynamic whole-body PET data. Repeat imaging occurred within 7 days. Relevant quantitative metrics were extracted from lesions and normal organs. Repeatability was assessed via mean test-retest percent changes [T-RT %Δ], within-subject coefficients of variation (wCVs), and intra-class correlation coefficients (ICCs). RESULTS: Nine subjects (mean age, 61.7 ± 6.2 years; 6 females) completed the test-retest protocol. Four subjects collectively had 17 [18F]FDG-avid lesions. Lesion wCVs were higher (i.e., worse repeatability) for PS-early-max (16.2%) and PS-early-peak (15.6%) than for SUV-early-max (8.9%) and SUV-early-peak (8.1%), with similar early metric ICCs (0.95-0.98). Lesion wCVs were similar for PS-late-max (8.5%) and PS-late-peak (6.4%) relative to SUV-late-max (9.7%) and SUV-late-peak (7.2%), with similar late metric ICCs (0.93-0.98). There was a significant bias toward higher retest SUV and PS values in the lesion analysis (T-RT %Δ [95% CI]: SUV-late-max, 10.0% [2.6%, 17.0%]; PS-late-max, 20.4% [14.3%, 26.4%]) but not in the normal organ analysis. CONCLUSIONS: Among [18F]FDG-avid lesions, the repeatability of PS-based metrics is similar to equivalent SUV-based metrics at late post-injection time points, indicating that PS-based metrics may be suitable for tracking response to oncologic therapies. However, further validation is required in light of our study's limitations, including small sample size and bias toward higher retest values for some metrics.

Australian physiotherapists attitudes, perceptions, and behaviours towards psychosocial screening tools: a qualitative interpretive description study.

PURPOSE: Psychosocial factors are a barrier to recovery for people with musculoskeletal pain and psychosocial screening tools are consistently recommended by best practice guidelines to assist in identification. However, many physiotherapists do not use these tools. Presently, the perspectives on psychosocial screening tools of Australian physiotherapists are unknown. Exploration of these factors may create targets for increased uptake. The purpose of this paper is to qualitatively explore Australian physiotherapists' attitudes, perceptions, and behaviours towards psychosocial screening tools for musculoskeletal pain conditions. MATERIALS AND METHODS: An Interpretive description qualitative study design was employed. Seventeen Australian physiotherapists were interviewed about their attitudes, perceptions, and behaviours towards psychosocial screening tools. Interviews were transcribed verbatim and analysed according to interpretive description. RESULTS: Analysis highlighted three major themes: (1) understanding the patient through psychosocial screening, (2) confidence and competence with psychosocial factors, and (3) factors outside of my control influence screening. CONCLUSIONS: This study presents a deeper understanding of Australian physiotherapists' diverse attitudes and practices regarding psychosocial screening tools. The research highlights not only the variability in perspectives towards the relevance of psychosocial factors in patient assessments, but also the influence of external elements such as patient demographics and clinic culture on the utilization of these screening methods.

Australian physiotherapists' varying attitudes and limited understanding of the impact of psychosocial factors may hinder the use of recommended psychosocial screening.Concerns about scope of practice, tool appropriateness for different patients, and clinic culture further challenge the integration of psychosocial assessments.The findings from this study indicate the need to provide more education to Australian physiotherapists on the importance and use of psychosocial risk factor screening, as part of clinical care standards and best practice guidelines in the management of patients, with musculoskeletal pain conditions.The findings from this study can support the creation of targeted training/innovations to improve the uptake of screening tools in Australian musculoskeletal clinical practice, to improve the care of patients with musculoskeletal pain conditions.

Comparison of tracer kinetic models for 68Ga-PSMA-11 PET in intermediate-risk primary prostate cancer patients.

BACKGROUND: 68Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and quantified as standard uptake values (SUVs) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology. This study was undertaken to evaluate the suitability of various kinetic models for 68Ga-PSMA-11 PET analysis. Twenty-three lesions in 18 patients were included in a retrospective kinetic evaluation of 55-min dynamic 68Ga-PSMA-11 pre-prostatectomy PET scans from patients with biopsy-demonstrated intermediate- to high-risk prostate cancer. Three kinetic models-a reversible one-tissue compartment model, an irreversible two-tissue compartment model, and a reversible two-tissue compartment model, were evaluated for their goodness of fit to lesion and normal reference prostate time-activity curves. Kinetic parameters obtained through graphical analysis and tracer kinetic modeling techniques were compared for reference prostate tissue and lesion regions of interest. RESULTS: Supported by goodness of fit and information loss criteria, the irreversible two-tissue compartment model optimally fit the time-activity curves. Lesions exhibited significant differences in kinetic rate constants (K1, k2, k3, Ki) and semiquantitative measures (SUV and %ID/kg) when compared with reference prostatic tissue. The two-tissue irreversible tracer kinetic model was consistently appropriate across prostatic zones. CONCLUSIONS: An irreversible tracer kinetic model is appropriate for dynamic analysis of 68Ga-PSMA-11 PET images. Kinetic parameters estimated by Patlak graphical analysis or full compartmental analysis can distinguish tumor from normal prostate tissue.

Comparing the Efficacy of Targeted and Blast Portal Messaging in Message Opening Rate and Anticoagulation Initiation in Patients With Atrial Fibrillation in the Preventing Preventable Strokes Study II: Prospective Cohort Study.

BACKGROUND: The gap in anticoagulation use among patients with atrial fibrillation (AF) is a major public health threat. Inadequate patient education contributes to this gap. Patient portal-based messaging linked to educational materials may help bridge this gap, but the most effective messaging approach is unknown. OBJECTIVE: This study aims to compare the responsiveness of patients with AF to an AF or anticoagulation educational message between 2 portal messaging approaches: sending messages targeted at patients with upcoming outpatient appointments 1 week before their scheduled appointment (targeted) versus sending messages to all eligible patients in 1 blast, regardless of appointment scheduling status (blast), at 2 different health systems: the University of Massachusetts Chan Medical School (UMass) and the University of Florida College of Medicine-Jacksonville (UFL). METHODS: Using the 2 approaches, we sent patient portal messages to patients with AF and grouped patients by high-risk patients on anticoagulation (group 1), high-risk patients off anticoagulation (group 2), and low-risk patients who may become eligible for anticoagulation in the future (group 3). Risk was classified based on the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age between 65 and 74 years, and sex category (CHA2DS2-VASc) score. The messages contained a link to the Upbeat website of the Heart Rhythm Society, which displays print and video materials about AF and anticoagulation. We then tracked message opening, review of the website, anticoagulation use, and administered patient surveys across messaging approaches and sites using Epic Systems (Epic Systems Corporation) electronic health record data and Google website traffic analytics. We then conducted chi-square tests to compare potential differences in the proportion of patients opening messages and other evaluation metrics, adjusting for potential confounders. All statistical analyses were performed in SAS (version 9.4; SAS Institute). RESULTS: We sent 1686 targeted messages and 1450 blast messages. Message opening was significantly higher with the targeted approach for patients on anticoagulation (723/1156, 62.5% vs 382/668, 57.2%; P=.005) and trended the same in patients off anticoagulation; subsequent website reviews did not differ by messaging approach. More patients off anticoagulation at baseline started anticoagulation with the targeted approach than the blast approach (adjusted percentage 9.3% vs 2.1%; P<.001). CONCLUSIONS: Patients were more responsive in terms of message opening and subsequent anticoagulation initiation with the targeted approach.

Modeling methyl-sensitive transcription factor motifs with an expanded epigenetic alphabet.

BACKGROUND: Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription factors can distinguish between unmodified and modified bases. Current models of transcription factor binding tend not to take DNA modifications into account, while the recent few that do often have limitations. This makes a comprehensive and accurate profiling of transcription factor affinities difficult. RESULTS: Here, we develop methods to identify transcription factor binding sites in modified DNA. Our models expand the standard A/C/G/T DNA alphabet to include cytosine modifications. We develop Cytomod to create modified genomic sequences and we also enhance the MEME Suite, adding the capacity to handle custom alphabets. We adapt the well-established position weight matrix (PWM) model of transcription factor binding affinity to this expanded DNA alphabet. Using these methods, we identify modification-sensitive transcription factor binding motifs. We confirm established binding preferences, such as the preference of ZFP57 and C/EBPß for methylated motifs and the preference of c-Myc for unmethylated E-box motifs. CONCLUSIONS: Using known binding preferences to tune model parameters, we discover novel modified motifs for a wide array of transcription factors. Finally, we validate our binding preference predictions for OCT4 using cleavage under targets and release using nuclease (CUT&RUN) experiments across conventional, methylation-, and hydroxymethylation-enriched sequences. Our approach readily extends to other DNA modifications. As more genome-wide single-base resolution modification data becomes available, we expect that our method will yield insights into altered transcription factor binding affinities across many different modifications.

The incidence and characteristics of heading in the 2019 FIFA Women's World Cup™.

INTRODUCTION: To quantify the incidence and characteristics of purposeful heading and other head impacts in professional women's football at the 2019 FIFA Women's World Cup™. METHODS: This cross-sectional cohort study analysed purposeful headers (uncontested and contested) and their characteristics (e.g. playing position, match situation, field location, and distance ball travelled), and other head impact events using video analysis. Total headers and head impact events, and incidence rate (IR) per 1000 match-hours were calculated for countries, positions, and other characteristics, such as location on the pitch. RESULTS: Purposeful headers accounted for 76% of all coded events (uncontested: 71%; contested: 29%), followed by attempted headers (21%), unintentional ball-head impacts (2%), and other head impacts (1%). Headers ranged from 0 to 22 per player, per match with a mean of 4.8 [±1.2]. Of all field positions, centrebacks had the highest heading rates and wingers the lowest. Strikers performed significantly more contested headers than any other position, and significantly less uncontested headers. Most headers occurred in the middle third (48%), from free game play (72%) and from long balls (>20 m) (68%). CONCLUSION: The findings of this study could assist the development of player heading risk profiles, sex-specific heading guidelines, and coaching practices.

Position Statement: Range Orders in the Management of Pain.

American Society for Pain Management Nursing (ASPMN) supports safe medication practices and the appropriate use of pro re nata (PRN) range orders for analgesics in the management of pain within the scope of nursing practice. Although range orders may apply to many medications prescribed as PRN, the focus of this ASPMN position statement is on PRN analgesic medication. PRN range orders are commonly used to provide flexibility in dosing to meet the analgesic requirements of an individual patient. There are many patient-specific factors that require professional clinical assessment when administering medications to patients. Unfortunately, several myths persist regarding The Joint Commission's (TJC) standard around the implementation of range orders leading many to assume that range orders are not supported or safe. On the contrary, if utilized in a consistent and appropriate manner, PRN range orders can allow nurses to provide optimal pain management while still providing safe administration (Paquette et al., 2022).

Ovarian Leydig Cell Tumor Associated with Recurrent Torsion and Virilization in an Adolescent Patient.

Ovarian tumors are rare in children; however, their incidence increases with age. Of these ovarian tumors, Leydig cell tumors are some of the rarest, accounting for less than 0.1% of all ovarian tumors across all ages. Leydig cell tumors predominantly occur in postmenopausal women and are characterized by nodular proliferation of Leydig cells in the ovarian hilum with intracytoplasmic Reinke crystals. These tumors secrete androgens, which can disrupt ovarian function, clinically presenting with abnormal uterine bleeding and virilization. Although they are generally benign, current recommendations are for treatment with a unilateral salpingo-oophorectomy. In adolescents, hyperandrogenism is most commonly caused by polycystic ovarian syndrome (PCOS); however, the differential for hyperandrogenism is broad. We present a case of a 15-year-old girl with a history of primary amenorrhea who presented with a Leydig cell tumor associated with recurrent ovarian torsion and virilization. This case reviews the challenges with diagnosis, management, and future implications of a rare androgen-secreting tumor in young patients.

How Movement Is Assessed Matters. Changes in Forward Bending During Cognitive Functional Therapy Treatment for People With Chronic Low Back Pain.

OBJECTIVE: To investigate forward bending range of motion (ROM) and velocity in patients with low back pain who were receiving Cognitive Functional Therapy and determine (1) the amount and timing of change occurring at the trunk and pelvis (global angles), and lumbar spine (intersensor angle), and (2a) differences in changes between participants with and without sensor biofeedback, and (2b) participants with and without baseline movement limitation. DESIGN: Observational study. METHODS: Two hundred sixty-one participants attended Cognitive Functional Therapy treatment and wore sensors at the T12 and S2 spine levels while performing forward bending. Measures included ROM and velocity from both sensors, and the intersensor angle. Regression models estimated changes over time. Time-group interactions tested participants who were subgrouped by treatment and baseline movement. RESULTS: During the 90-day evaluation period, most change occurred in the first 21 days. Changes in ROM observed at T12 (3.3°, 95% CI: 1.0°, 5.5°; P = .001) and S2 (3.3°, 95% CI: 1.2°, 5.4°; P = .002) were similar. Intersensor angle remained similar (0.2°, 95% CI: -2.0°, -1.6°; P = .81). Velocity measured at T12 and S2, and the intersensor angle increased 8.5°/s (95% CI: 6.7°/s, 10.3°/s; P<.0001), 5.3°/s (95% CI: 4.0°/s, 6.5°/s; P<.0001), and 3.4°/s (95% CI: 2.4°/s, 4.5°/s; P<.0001), respectively, for 0 to 21 days. There were minimal differences in participants who received biofeedback. Larger increases occurred in participants with restricted ROM and slower velocity at baseline. CONCLUSION: During 0 to 21 days, we observed changes at the trunk and pelvis (especially in people with reduced ROM), and velocity changes across all measures (especially in people with baseline movement limitations). Biofeedback did not augment the changes. When targeting forward bending in people with low back pain, clinicians should monitor changes in velocity and global ROM. J Orthop Sports Phys Ther 2024;54(3):1-13. Epub 19 December 2023. doi:10.2519/jospt.2023.12023.

Epigenetic control and genomic imprinting dynamics of the Dlk1-Dio3 domain.

Genomic imprinting is an epigenetic process whereby genes are monoallelically expressed in a parent-of-origin-specific manner. Imprinted genes are frequently found clustered in the genome, likely illustrating their need for both shared regulatory control and functional inter-dependence. The Dlk1-Dio3 domain is one of the largest imprinted clusters. Genes in this region are involved in development, behavior, and postnatal metabolism: failure to correctly regulate the domain leads to Kagami-Ogata or Temple syndromes in humans. The region contains many of the hallmarks of other imprinted domains, such as long non-coding RNAs and parental origin-specific CTCF binding. Recent studies have shown that the Dlk1-Dio3 domain is exquisitely regulated via a bipartite imprinting control region (ICR) which functions differently on the two parental chromosomes to establish monoallelic expression. Furthermore, the Dlk1 gene displays a selective absence of imprinting in the neurogenic niche, illustrating the need for precise dosage modulation of this domain in different tissues. Here, we discuss the following: how differential epigenetic marks laid down in the gametes cause a cascade of events that leads to imprinting in the region, how this mechanism is selectively switched off in the neurogenic niche, and why studying this imprinted region has added a layer of sophistication to how we think about the hierarchical epigenetic control of genome function.

Comparison of Tracer Kinetic Models for 68Ga-PSMA-11 PET in Intermediate Risk Primary Prostate Cancer Patients.

BACKGROUND: 68Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and quantified as standard uptake values (SUV) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology. This study was undertaken to evaluate the suitability of various kinetic models for 68Ga-PSMA-11 PET analysis. Twenty-three lesions in 18 patients were included in a retrospective kinetic evaluation of 55-minute dynamic 68Ga-PSMA-11 pre-prostatectomy PET scans from patients with biopsy-demonstrated intermediate to high-risk prostate cancer. A reversible one-tissue compartment model, irreversible two-tissue compartment model, and a reversible two-tissue compartment model were evaluated for their goodness-of-fit to lesion and normal reference prostate time-activity curves. Kinetic parameters obtained through graphical analysis and tracer kinetic modeling techniques were compared for reference prostate tissue and lesion regions of interest. RESULTS: Supported by goodness-of-fit and information loss criteria, the irreversible two-tissue compartment model was selected as optimally fitting the time-activity curves. Lesions exhibited significant differences in kinetic rate constants (K1, k2, k3, Ki) and semiquantitative measures (SUV) when compared with reference prostatic tissue. The two-tissue irreversible tracer kinetic model was consistently appropriate across prostatic zones. CONCLUSIONS: An irreversible tracer kinetic model is appropriate for dynamic analysis of 68Ga-PSMA-11 PET images. Kinetic parameters estimated by Patlak graphical analysis or full compartmental analysis can distinguish tumor from normal prostate tissue.

Neuromuscular adaptations of swallowing and speech in unilateral cerebral palsy: shared and distinctive traits.

Our aims were to 1) examine the neuromuscular control of swallowing and speech in children with unilateral cerebral palsy (UCP) compared with typically developing children (TDC), 2) determine shared and separate neuromuscular underpinnings of the two functions, and 3) explore the relationship between this control and behavioral outcomes in UCP. Surface electromyography (sEMG) was used to record muscle activity from the submental and superior and inferior orbicularis oris muscles during standardized swallowing and speech tasks. The variables examined were normalized mean amplitude, time to peak amplitude, and bilateral synchrony. Swallowing and speech were evaluated using standard clinical measures. Sixteen children with UCP and 16 TDC participated (7-12 yr). Children with UCP demonstrated higher normalized mean amplitude and longer time to peak amplitude across tasks than TDC (P < 0.01; and P < 0.02) and decreased bilateral synchrony than TDC for swallows (P < 0.01). Both shared and distinctive neuromuscular patterns were observed between swallowing and speech. In UCP, higher upper lip amplitude during swallows was associated with shorter normalized mealtime durations, whereas higher submental bilateral synchrony was related to longer mealtime durations. Children with UCP demonstrate neuromuscular adaptations for swallowing and speech, which should be further evaluated for potential treatment targets. Furthermore, both shared and distinctive neuromuscular underpinnings between the two functions are documented.NEW & NOTEWORTHY Systematically studying the swallowing and speech of children with UCP is new and noteworthy. We found that they demonstrate neuromuscular adaptations for swallowing and speech compared with typically developing peers. We examined swallowing and speech using carefully designed tasks, similar in motor complexity, which allowed us to directly compare patterns. We found shared and distinctive neuromuscular patterns between swallowing and speech.

Epigenetic inheritance is unfaithful at intermediately methylated CpG sites.

DNA methylation at the CpG dinucleotide is considered a stable epigenetic mark due to its presumed long-term inheritance through clonal expansion. Here, we perform high-throughput bisulfite sequencing on clonally derived somatic cell lines to quantitatively measure methylation inheritance at the nucleotide level. We find that although DNA methylation is generally faithfully maintained at hypo- and hypermethylated sites, this is not the case at intermediately methylated CpGs. Low fidelity intermediate methylation is interspersed throughout the genome and within genes with no or low transcriptional activity, and is not coordinately maintained between neighbouring sites. We determine that the probabilistic changes that occur at intermediately methylated sites are likely due to DNMT1 rather than DNMT3A/3B activity. The observed lack of clonal inheritance at intermediately methylated sites challenges the current epigenetic inheritance model and has direct implications for both the functional relevance and general interpretability of DNA methylation as a stable epigenetic mark.

Pharmacological characterization of SAGE-718, a novel positive allosteric modulator of N-methyl-d-aspartate receptors.

BACKGROUND AND PURPOSE: Select neuroactive steroids tune neural activity by modulating excitatory and inhibitory neurotransmission, including the endogenous cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC), which is an N-methyl-d-aspartate (NMDA) receptor positive allosteric modulator (PAM). NMDA receptor PAMs are potentially an effective pharmacotherapeutic strategy to treat conditions associated with NMDA receptor hypofunction. EXPERIMENTAL APPROACH: Using in vitro and in vivo electrophysiological recording experiments and behavioural approaches, we evaluated the effect of SAGE-718, a novel neuroactive steroid NMDA receptor PAM currently in clinical development for the treatment of cognitive impairment, on NMDA receptor function and endpoints that are altered by NMDA receptor hypoactivity and assessed its safety profile. KEY RESULTS: SAGE-718 potentiated GluN1/GluN2A-D NMDA receptors with equipotency and increased NMDA receptor excitatory postsynaptic potential (EPSP) amplitude without affecting decay kinetics in striatal medium spiny neurons. SAGE-718 increased the rate of unblock of the NMDA receptor open channel blocker ketamine on GluN1/GluN2A in vitro and accelerated the rate of return on the ketamine-evoked increase in gamma frequency band power, as measured with electroencephalogram (EEG), suggesting that PAM activity is driven by increased channel open probability. SAGE-718 ameliorated deficits due to NMDA receptor hypofunction, including social deficits induced by subchronic administration of phencyclidine, and behavioural and electrophysiological deficits from cholesterol and 24(S)-HC depletion caused by 7-dehydrocholesterol reductase inhibition. Finally, SAGE-718 did not produce epileptiform activity in a seizure model or neurodegeneration following chronic dosing. CONCLUSIONS AND IMPLICATIONS: These findings provide strong evidence that SAGE-718 is a neuroactive steroid NMDA receptor PAM with a mechanism that is well suited as a treatment for conditions associated with NMDA receptor hypofunction.

Mammary adipocyte flow cytometry as a tool to study mammary gland biology.

The mammary gland is a vital exocrine organ that has evolved in mammals to secrete milk and provide nutrition to ensure the growth and survival of the neonate The mouse mammary gland displays extraordinary plasticity each time the female undergoes pregnancy and lactation, including a sophisticated process of tertiary branching and alveologenesis to form a branched epithelial tree and subsequently milk-producing alveoli. Upon the cessation of lactation, the gland remodels back to a simple ductal architecture via highly regulated involution processes. At the cellular level, the plasticity is characterised by proliferation of mammary cell populations, differentiation and apoptosis, accompanied by major changes in cell function and morphology. The mammary epithelium requires a specific stromal environment to grow, known as the mammary fat pad. Mammary adipocytes are one of the most prominent cell types in the fat pad, but despite their vast proportion in the tissue and their crucial interaction with epithelial cells, their physiology remains largely unknown. Over the past decade, the need to understand the properties and contribution of mammary adipocytes has become more recognised. However, the development of adequate methods and protocols to study this cellular niche is still lagging, partially due to their fragile nature, the difficulty of isolating them, the lack of reliable cell surface markers and the heterogenous environment in this tissue, which differs from other adipocyte depots. Here, we describe a new rapid and simple flow cytometry protocol specifically designed for the analysis and isolation of mouse mammary adipocytes across mammary gland developmental stages.

Process of change for people with knee osteoarthritis undergoing cognitive functional therapy: a replicated single-case experimental design study.

PURPOSE: To examine the applicability and process of change of Cognitive Functional Therapy (CFT) in the management of pain and disability in people with knee osteoarthritis who were offered knee replacement surgery and had risk factors for poor response to surgery. METHODS: Single-case experimental design with a mixed-methods, repeated measures approach was used to investigate the process of change through CFT in four participants. Qualitative interviews investigated beliefs, behaviours and coping responses, and self-reported measures assessed pain, disability, psychological factors, and function at 25 timepoints. Study registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12619001491156). RESULTS: Qualitative data indicate that CFT promoted helpful changes in all participants, with two responses observed. One reflected a clear shift to a biopsychosocial conceptualisation of osteoarthritis, behavioural re-engagement and the view that a knee replacement was no longer necessary. The other response reflected a mixed conceptualisation with dissonant beliefs about osteoarthritis and its management. Psychological and social factors were identified as potential treatment barriers. Overall, quantitative measures supported the qualitative findings. CONCLUSION: The process of change varies between and within individuals over time. Psychological and social barriers to treatment have implications for future intervention studies for the management of knee osteoarthritis.IMPLICATIONS FOR REHABILITATIONCognitive Functional Therapy is applicable in the management of knee osteoarthritis.Reconceptualisation of osteoarthritis reflected a helpful change.Psychological and social factors emerged as barriers to recovery.

Diagnostic Performance of Dynamic Whole-Body Patlak [18F]FDG-PET/CT in Patients with Indeterminate Lung Lesions and Lymph Nodes.

BACKGROUND: Static [18F]FDG-PET/CT is the imaging method of choice for the evaluation of indeterminate lung lesions and NSCLC staging; however, histological confirmation of PET-positive lesions is needed in most cases due to its limited specificity. Therefore, we aimed to evaluate the diagnostic performance of additional dynamic whole-body PET. METHODS: A total of 34 consecutive patients with indeterminate pulmonary lesions were enrolled in this prospective trial. All patients underwent static (60 min p.i.) and dynamic (0-60 min p.i.) whole-body [18F]FDG-PET/CT (300 MBq) using the multi-bed-multi-timepoint technique (Siemens mCT FlowMotion). Histology and follow-up served as ground truth. Kinetic modeling factors were calculated using a two-compartment linear Patlak model (FDG influx rate constant = Ki, metabolic rate = MR-FDG, distribution volume = DV-FDG) and compared to SUV using ROC analysis. RESULTS: MR-FDGmean provided the best discriminatory power between benign and malignant lung lesions with an AUC of 0.887. The AUC of DV-FDGmean (0.818) and SUVmean (0.827) was non-significantly lower. For LNM, the AUCs for MR-FDGmean (0.987) and SUVmean (0.993) were comparable. Moreover, the DV-FDGmean in liver metastases was three times higher than in bone or lung metastases. CONCLUSIONS: Metabolic rate quantification was shown to be a reliable method to detect malignant lung tumors, LNM, and distant metastases at least as accurately as the established SUV or dual-time-point PET scans.