Intra-marrow delivery of human interleukin-6-loaded biodegradable microspheres promotes growth of patient-derived multiple myeloma cells in mice.

Not available.

Injury-inciting circumstances of sudden-onset hamstring injuries: video analyses of 63 match injuries in male professional football players in the Qatar Stars League (2013-2020).

OBJECTIVE: To describe and categorise the injury-inciting circumstances of sudden-onset hamstring match injuries in professional football players using systematic video analysis. METHODS: Using a prospective injury surveillance database, all sudden-onset hamstring match injuries in male football players (18 years and older) from the Qatar Stars League between September 2013 and August 2020 were reviewed and cross-referenced with broadcasted match footage. Videos with a clear observable painful event (ie, a player grabbing their posterior thigh) were included. Nine investigators independently analysed all videos to describe and categorise injury-inciting circumstances. We used three main categories: playing situation (eg, time of injury), player action(s) (eg, running) and other considerations (eg, contact). Player action(s) and other considerations were not mutually exclusive. RESULTS: We included 63 sudden-onset hamstring match injuries out of 295 registered injuries between 2013 and 2020. Running was involved in 86% of injuries. Hamstring injuries occurred primarily during acceleration of 0-10 m (24% of all injuries) and in general at different running distances (0-50 m) and speeds (slow to fast). At 0-10 m distance, indirect player-to-player contact and inadequate balance were involved in 53% and 67% of the cases, respectively. Pressing occurred in 46% of all injuries (injured player pressing opponent: 25%; being pressed by opponent: 21%) and frequently involved player-to-player contact (69% of the cases when the injured player was pressing vs 15% of the cases when the opponent was pressing) and inadequate balance (82% vs 50%, respectively). Other player actions that did not involve running (n=9, 14% of all injuries) were kicking (n=6) and jumping (n=3). CONCLUSION: The injury-inciting circumstances of sudden-onset hamstring match injuries in football varied. The most common single-player action (24%) was acceleration over a distance of <10 m. Pressing, inadequate balance and indirect contact were frequently seen player actions. Injury prevention research in football should look beyond high-speed running as the leading risk factor for sudden-onset hamstring injuries.

MRI paraspinous skeletal muscle enhancement: A potential imaging biomarker for assessing clinical liver cirrhosis severity.

PURPOSE: To evaluate for correlation between MRI paraspinous muscle (PSM) enhancement and clinical measures of cirrhosis severity (CMCS) utilizing established imaging biomarkers of sarcopenia as comparison. MATERIALS AND METHODS: Retrospective evaluation of 224 patients (mean age 59.6± 9.7 years, 135 males and 89 females) with liver cirrhosis who underwent contrast-enhanced MRI between August 2021 and August 2022 was performed. Assessed variables included: body mass index (BMI), varices and ascites present on imaging (VPI and API), albumin, total bilirubin (Tbili), international normalized ratio (INR), creatinine, MELD score, as well as history of paracentesis (PH), spontaneous bacterial peritonitis, and variceal bleed (VBH). These variables were compared to PSM skeletal muscle index (SMI), PSM signal fat fractions (sFF), and PSM contrast enhancement fraction (CEFR) calculated on arterial (CEFR-ART), portal venous (CEFR-PV), and delayed (CEFR-DEL) phases collected on MRI. RESULTS: Patients with MELD>17, PH, and VPI had lower PSM CEFR-ART (0.06vs. 0.11, p = 0.01; 0.07vs. 0.11, p = 0.01; and 0.09vs. 0.13, p = 0.03, respectively). PSM CEFR-ART correlated negatively with MELD. Patients with MELD>17 and PH had lower PSM CEFR-PV (0.16vs. 0.23, p = 0.02; 0.18 vs. 0.23, p = 0.01, respectively). PSM CEFR-PV correlated positively with albumin and negatively with Tbili, INR, and MELD. PSM CEFR-DEL correlated negatively with Tbili and MELD. Patients with API, PH, and VBH had lower PSM SMI (4.68vs. 5.59, p<0.001; 4.37vs. 5.48, p<0.001; 4.78vs. 5.35, p = 0.04, respectively). PSM SMI correlated negatively with Tbili and positively with BMI. PSM sFF correlated positively with BMI, PSM CEFR-PV, and PSM CEFR-DEL. CONCLUSION: PSM CEFR is significantly reduced on MRI in patients with clinical manifestations of severe liver cirrhosis. Further investigation into PSM CEFR's usefulness as an imaging biomarker for evaluating liver disease severity is warranted.

When the Clock Strikes A-fib.

Within the broad spectrum of atrial fibrillation (AF) symptomatology, there is a striking subset of patients with predominant or even solitary nocturnal onset of the arrhythmia. This review covers AF with nocturnal onset, with the aim of defining this distinctive subgroup among patients with AF. A periodicity analysis is provided showing a clear increased onset between 10:00 pm and 7:00 am. Multiple interacting mechanisms are discussed, such as circadian modulation of electrophysiological properties, vagal tone, and sleep disorders, as well as the potential interaction and synergism between these factors, to provide a better understanding of this clinical entity. Lastly, potential therapeutic targets for AF with nocturnal onset are addressed such as upstream therapy for underlying comorbidities, type of drug and timing of drug administration and pulmonary vein isolation, ablation of the ganglionated plexus, and autonomic nervous system modulation. Understanding the underlying AF mechanisms in the individual patient with nocturnal onset will contribute to patient-specific therapy.

Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease.

The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography and subthalamic local field potential recordings were performed OFF therapy (n = 22), ON dopaminergic medication (n = 18) and on subthalamic deep brain stimulation (n = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography. In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders.

Establishing a surveillance programme for Salmonella Dublin in Austrian dairy herds by comparing herd-level vs. individual animal detection methods.

Due to its increasing occurrence in cattle farms in various countries, leading to significant economic losses in affected livestock, Salmonella enterica subspecies enterica serovar Dublin (S. Dublin) has become a highly investigated pathogen in cattle production. In Austria, there have been occasional human cases of S. Dublin as well as an increase in laboratory-confirmed cases in cattle, indicating the need for a screening programme to determine the current status in Austria. The aims of this study were, firstly, to determine the seroprevalence of S. Dublin in dairy herds through bulk milk screenings in two federal states (Salzburg, Tyrol) of Austria. Secondly, the study aimed to identify the infection status of the herds through individual animal and herd level detection, comparing microbiological, molecular and serological detection methods. The results of the study will allow the development of a sampling strategy for a surveillance programme in Austria. A total of 6973 dairy farms were tested through serological bulk milk screening. The seroprevalence for the federal state of Tyrol was 14.8 % and for Salzburg it was 18.2 %, resulting in an average seroprevalence of 16.5 %. At an individual animal level, 205 (11.3 %) animals tested positive for shedding of S. Dublin in the faeces through microbiological detection, and 268 (17.0 %) animals had positive values (ct value ≤ 38) by qPCR. The association between microbiological and molecular detection was statistically significant (p < 0.001), with a calculated kappa value of 0.65 ± 0.27 (p ≤ 0.001), assuming a substantial level of agreement. In 17 herds, where an individual animal tested positive for shedding of S. Dublin, environmental sampling and testing were carried out. At a herd level 16 (94.1 %) out of the 17 participating herds, tested positive for S. Dublin either microbiologically or by molecular assay in boot swab samples. Bulk milk samples from 14 out of the 17 participating herds were analysed for antibodies to S. Dublin and 12 samples (85.7 %) were positive. In total 111 (18.9 %) out of 587 blood samples tested positive for S. Dublin antibodies, demonstrating a statistically significant correlation (p < 0.001) both with microbiological (κ = 0.32 ± 0.49; p ≤ 0.001) and molecular (κ=0.23 ± 0.06; p ≤ 0.001) findings. It was possible to identify S. Dublin by culture from boot swabs in 14 (82.4 %) out of 17 herds and by molecular assay using qPCR in 15 (88.2 %) out of 17 herds, indicating a suitable sample type for screening on a herd level-basis for acute infections, but not for identifying chronic infections or asymptomatic carriers. Other environmental samples, such as sponge-sticks, are only suitable to a limited extent for the detection of S. Dublin. The results of this study demonstrate a moderate S. Dublin prevalence in dairy herds in the selected Austrian regions, signalling further screening and management programmes for the future.

Normal hip strength and range of motion values in youth and adult female national football teams: Data from 504 assessments.

OBJECTIVES: To determine normal hip adduction- and abduction strength and range of motion (ROM) values for youth and adult female national team football players, and evaluate if increasing age, playing position and leg dominance were associated with these strength and ROM values. DESIGN: Cohort study. SETTING: National football center. PARTICIPANTS: 344 unique asymptomatic female football players. MAIN OUTCOME MEASURES: Hip internal/external rotation (°), Bent Knee Fall Out test (cm), hip adduction/abduction strength(N) and ratio, and normalised hip adduction/abduction torque (Nm/kg). RESULTS: A total of 504 assessments were performed. A total of 107 players underwent two (n = 67), three (n = 27) or four (n = 13) assessments. Mean peak hip adduction strength was 39% greater in 20 + Y old players 170 (±53 N) than in 13Y old players 122 (±28 N). Normalised hip adduction torque was 9% greater: 2.5 (±0.8Nm/kg) versus 2.3 (±0.5Nm/kg). A positive association between age and all strength measurements was found, while a negative association between age and hip external rotation and total hip rotation was found. No clinically relevant differences were found for the associations between playing position, leg dominance and hip strength- and ROM values. CONCLUSION: Normal values for hip strength and range of motion in youth and adult female national football players are presented that can be used as clinical reference values.

(Cost-)effectiveness of personalised multimodal physiotherapy compared to surgery in patients with cervical radiculopathy: A systematic review.

RATIONALE: Cervical radiculopathy is initially typically managed conservatively. Surgery is indicated when conservative management fails or with severe/progressive neurological signs. Personalised multimodal physiotherapy could be a promising conservative strategy. However, aggregated evidence on the (cost-)effectiveness of personalised multimodal physiotherapy compared to surgery with/without post-operative physiotherapy is lacking. AIM/OBJECTIVES: To systematically summarise the literature on the (cost-)effectiveness of personalised multimodal physiotherapy compared to surgery with or without post-operative physiotherapy in patients with cervical radiculopathy. METHODS: PubMed, Embase, CINAHL, PsycINFO and Web of Science were searched from inception to 1st of March 2023. Primary outcomes were effectiveness regarding costs, arm pain intensity and disability. Neck pain intensity, perceived recovery, quality of life, neurological symptoms, range-of-motion, return-to-work, medication use, (re)surgeries and adverse events were considered secondary outcomes. Randomised clinical trials comparing personalised multimodal physiotherapy versus surgical approaches with/without post-operative physiotherapy were included. Two independent reviewers performed study selection, data-extraction, and risk of bias assessment using the Cochrane RoB 2 and Consolidated Health Economic Evaluation Reporting Standards statement. Certainty of the evidence was determined using Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: From 2109 records, eight papers from two original trials, with 117 participants in total were included. Low certainty evidence showed there were no significant differences on arm pain intensity and disability, except for the subscale 'heavy work' related disability (12 months) and disability at 5-8 years. Cost-effectiveness was not assessed. There was low certainty evidence that physiotherapy improved significantly less on neck pain intensity, sensory loss and perceived recovery compared to surgery with/without physiotherapy. Low certainty evidence showed there were no significant differences on numbness, range of motion, medication use, and quality of life. No adverse events were reported. CONCLUSION: Considering the clinical importance of accurate management recommendations and the current low level of certainty, high-quality cost-effectiveness studies are needed.

Separation of Damage Mechanisms in Full Forward Rod Extruded Case-Hardening Steel 16MnCrS5 Using 3D Image Segmentation.

In general, formed components are lightweight as well as highly economic and resource efficient. However, forming-induced ductile damage, which particularly affects the formation and growth of pores, has not been considered in the design of components so far. Therefore, an evaluation of forming-induced ductile damage would enable an improved design and take better advantage of the lightweight nature as it affects the static and dynamic mechanical material properties. To quantify the amount, morphology and distribution of the pores, advanced scanning electron microscopy (SEM) methods such as scanning transmission electron microscopy (STEM) and electron channeling contrast imaging (ECCI) were used. Image segmentation using a deep learning algorithm was applied to reproducibly separate the pores from inclusions such as manganese sulfide inclusions. This was achieved via layer-by-layer ablation of the case-hardened steel 16MnCrS5 (DIN 1.7139, AISI/SAE 5115) with a focused ion beam (FIB). The resulting images were reconstructed in a 3D model to gain a mechanism-based understanding beyond the previous 2D investigations.

dtool and dserver: A flexible ecosystem for findable data.

Making data FAIR-findable, accessible, interoperable, reproducible-has become the recurring theme behind many research data management efforts. dtool is a lightweight data management tool that packages metadata with immutable data to promote accessibility, interoperability, and reproducibility. Each dataset is self-contained and does not require metadata to be stored in a centralised system. This decentralised approach means that finding datasets can be difficult. dtool's lookup server, short dserver, as defined by a REST API, makes dtool datasets findable, hence rendering the dtool ecosystem fit for a FAIR data management world. Its simplicity, modularity, accessibility and standardisation via API distinguish dtool and dserver from other solutions and enable it to serve as a common denominator for cross-disciplinary research data management. The dtool ecosystem bridges the gap between standardisation-free data management by individuals and FAIR platform solutions with rigid metadata requirements.

Baseline clinical and MRI risk factors for hamstring reinjury showing the value of performing baseline MRI and delaying return to play: a multicentre, prospective cohort of 330 acute hamstring injuries.

OBJECTIVES: Studies identifying clinical and MRI reinjury risk factors are limited by relatively small sample sizes. This study aimed to examine the association between baseline clinical and MRI findings with the incidence of hamstring reinjuries using a large multicentre dataset. METHODS: We merged data from four prospective studies (three randomised controlled trials and one ongoing prospective case series) from Qatar and the Netherlands. Inclusion criteria included patients with MRI-confirmed acute hamstring injuries (<7 days). We performed multivariable modified Poisson regression analysis to assess the association of baseline clinical and MRI data with hamstring reinjury incidence within 2 months and 12 months of follow-up. RESULTS: 330 and 308 patients were included in 2 months (31 (9%) reinjuries) and 12 months (52 (17%) reinjuries) analyses, respectively. In the 2-month analysis, the presence of discomfort during the active knee extension test was associated with reinjury risk (adjusted risk ratio (ARR) 3.38; 95% CI 1.19 to 9.64). In the 12 months analysis, the time to return to play (RTP) (ARR 0.99; 95% CI 0.97 to 1.00), straight leg raise angle on the injured leg (ARR 0.98; 95% CI 0.96 to 1.00), the presence of discomfort during active knee extension test (ARR 2.52; 95% CI 1.10 to 5.78), the extent of oedema anteroposterior on MRI (ARR 0.74; 95% CI 0.57 to 0.96) and myotendinous junction (MTJ) involvement on MRI (ARR 3.10; 95% CI 1.39 to 6.93) were independently associated with hamstring reinjury. CONCLUSIONS: Two clinical findings (the presence of discomfort during active knee extension test, lower straight leg raise angle on the injured leg), two MRI findings (less anteroposterior oedema, MTJ involvement) and shorter time to RTP were independently associated with increased hamstring reinjury risk. These findings may assist the clinician to identify patients at increased reinjury risk following acute hamstring injury. TRIAL REGISTRATION NUMBERS: NCT01812564; NCT02104258; NL2643; NL55671.018.16.

Closed-loop automated drug infusion regulator: A clinically translatable, closed-loop drug delivery system for personalized drug dosing.

BACKGROUND: Dosing of chemotherapies is often calculated according to the weight and/or height of the patient or equations derived from these, such as body surface area (BSA). Such calculations fail to capture intra- and interindividual pharmacokinetic variation, which can lead to order of magnitude variations in systemic chemotherapy levels and thus under- or overdosing of patients. METHODS: We designed and developed a closed-loop drug delivery system that can dynamically adjust its infusion rate to the patient to reach and maintain the drug's target concentration, regardless of a patient's pharmacokinetics (PK). FINDINGS: We demonstrate that closed-loop automated drug infusion regulator (CLAUDIA) can control the concentration of 5-fluorouracil (5-FU) in rabbits according to a range of concentration-time profiles (which could be useful in chronomodulated chemotherapy) and over a range of PK conditions that mimic the PK variability observed clinically. In one set of experiments, BSA-based dosing resulted in a concentration 7 times above the target range, while CLAUDIA keeps the concentration of 5-FU in or near the targeted range. Further, we demonstrate that CLAUDIA is cost effective compared to BSA-based dosing. CONCLUSIONS: We anticipate that CLAUDIA could be rapidly translated to the clinic to enable physicians to control the plasma concentration of chemotherapy in their patients. FUNDING: This work was supported by MIT's Karl van Tassel (1925) Career Development Professorship and Department of Mechanical Engineering and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center.

Accelerated IVIM-corrected DTI in acute hamstring injury: towards a clinically feasible acquisition time.

BACKGROUND: Intravoxel incoherent motion (IVIM)-corrected diffusion tensor imaging (DTI) potentially enhances return-to-play (RTP) prediction after hamstring injuries. However, the long scan times hamper clinical implementation. We assessed accelerated IVIM-corrected DTI approaches in acute hamstring injuries and explore the sensitivity of the perfusion fraction (f) to acute muscle damage. METHODS: Athletes with acute hamstring injury received DTI scans of both thighs < 7 days after injury and at RTP. For a subset, DTI scans were repeated with multiband (MB) acceleration. Data from standard and MB-accelerated scans were fitted with standard and accelerated IVIM-corrected DTI approach using high b-values only. Segmentations of the injury and contralateral healthy muscles were contoured. The fitting methods as well as the standard and MB-accelerated scan were compared using linear regression analysis. For sensitivity to injury, Δ(injured minus healthy) DTI parameters between the methods and the differences between injured and healthy muscles were compared (Wilcoxon signed-rank test). RESULTS: The baseline dataset consisted of 109 athletes (16 with MB acceleration); 64 of them received an RTP scan (8 with MB acceleration). Linear regression of the standard and high-b DTI fitting showed excellent agreement. With both fitting methods, standard and MB-accelerated scans were comparable. Δ(injured minus healthy) was similar between standard and accelerated methods. For all methods, all IVIM-DTI parameters except f were significantly different between injured and healthy muscles. CONCLUSIONS: High-b DTI fitting with MB acceleration reduced the scan time from 11:08 to 3:40 min:s while maintaining sensitivity to hamstring injuries; f was not different between healthy and injured muscles. RELEVANCE STATEMENT: The accelerated IVIM-corrected DTI protocol, using fewer b-values and MB acceleration, reduced the scan time to under 4 min without affecting the sensitivity of the quantitative outcome parameters to hamstring injuries. This allows for routine clinical monitoring of hamstring injuries, which could directly benefit injury treatment and monitoring. KEY POINTS: • Combining high-b DTI-fitting and multiband-acceleration dramatically reduced by two thirds the scan time. • The accelerated IVIM-corrected DTI approaches maintained the sensitivity to hamstring injuries. • The IVIM-derived perfusion fraction was not sensitive to hamstring injuries.

Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

Acute clinical evaluation for the diagnosis of lateral ankle ligament injuries is useful: A comparison between the acute and delayed settings.

PURPOSE: To determine the diagnostic value of seven injury history variables, nine clinical tests (including the combination thereof) and overall clinical suspicion for complete discontinuity of the lateral ankle ligaments in the acute (0-2 days post-injury) and delayed setting (5-8 days post-injury). METHODS: All acute ankle injuries in adult athletes (≥18 years) presenting up to 2 days post-injury were assessed for eligibility. Athletes were excluded if imaging studies demonstrated a frank fracture or 3 T MRI could not be acquired within 10 days post-injury. Using standardized history variables and clinical tests, acute clinical evaluation was performed within 2 days post-injury. Delayed clinical evaluation was performed 5-8 days post-injury. Overall, clinical suspicion was recorded after clinical evaluation. MRI was used as the reference standard. RESULTS: Between February 2018 and February 2020, a total of 117 acute ankle injuries were screened for eligibility, of which 43 were included in this study. Complete discontinuity of lateral ankle ligaments was observed in 23 (53%) acute ankle injuries. In the acute setting, lateral swelling had 100% (95% confidence interval [CI]: 82-100) sensitivity, haematoma had 85% (95% CI: 61-96) specificity and the anterior drawer test had 100% (95% CI: 77-100) specificity. In the delayed setting, sensitivity for the presence of haematoma improved from 43% (95% CI: 24-65) to 91% (95% CI: 70-98; p < 0.01) and the sensitivity of the anterior drawer test improved from 21% (95% CI: 7-46) to 61% (95% CI: 39-80; p = 0.02). Clinical suspicion had a positive likelihood ratio (LR) of 4.35 (95% CI: 0.55-34.17) in the acute setting and a positive LR of 6.09 (95% CI: 1.57-23.60) in the delayed setting. CONCLUSIONS: In the acute setting, clinical evaluation can exclude complete discontinuity (e.g., absent lateral swelling) and identify athletes with a high probability of complete discontinuity (e.g., positive anterior drawer test) of the lateral ankle ligaments. In the delayed setting, the sensitivity of common clinical findings increases resulting in an improved diagnostic accuracy. In clinical practice, this study underlines the importance of meticulous clinical evaluation in the acute setting. LEVEL OF EVIDENCE: Level III.

Single threshold adaptive deep brain stimulation in Parkinson's disease depends on parameter selection, movement state and controllability of subthalamic beta activity.

BACKGROUND: Deep brain stimulation (DBS) is an invasive treatment option for patients with Parkinson's disease. Recently, adaptive DBS (aDBS) systems have been developed, which adjust stimulation timing and amplitude in real-time. However, it is unknown how changes in parameters, movement states and the controllability of subthalamic beta activity affect aDBS performance. OBJECTIVE: To characterize how parameter choice, movement state and controllability interactively affect the electrophysiological and behavioral response to single threshold aDBS. METHODS: We recorded subthalamic local field potentials in 12 patients with Parkinson's disease receiving single threshold aDBS in the acute post-operative state. We investigated changes in two aDBS parameters: the onset time and the smoothing of real-time beta power. Electrophysiological patterns and motor performance were assessed while patients were at rest and during a simple motor task. We further studied the impact of controllability on aDBS performance by comparing patients with and without beta power modulation during continuous stimulation. RESULTS: Our findings reveal that changes in the onset time control the extent of beta power suppression achievable with single threshold adaptive stimulation during rest. Behavioral data indicate that only specific parameter combinations yield a beneficial effect of single threshold aDBS. During movement, action induced beta power suppression reduces the responsivity of the closed loop algorithm. We further demonstrate that controllability of beta power is a prerequisite for effective parameter dependent modulation of subthalamic beta activity. CONCLUSION: Our results highlight the interaction between single threshold aDBS parameter selection, movement state and controllability in driving subthalamic beta activity and motor performance. By this means, we identify directions for the further development of closed-loop DBS algorithms.

Clinical examination tests for adductor- and pubic-related groin pain in athletes with longstanding groin pain: Inter-examiner reliability and prevalence of positive tests.

OBJECTIVES: Evaluate the inter-examiner reliability of pain provocation tests for hip adductors (palpation, stretch and resistance) and for pubic symphysis (palpation) in athletes with longstanding groin pain, and to determine the prevalence of positive tests. DESIGN: Inter-examiner reliability. SETTING: Orthopaedic and sports medicine hospital. PARTICIPANTS: Male athletes with longstanding groin pain. MAIN OUTCOME MEASURES: Inter-examiner reliability, absolute/positive/negative agreement, and the mean prevalence of positive tests for athletes classified with adductor- and pubic-related groin pain were calculated. RESULTS: We included 44 male athletes with longstanding groin pain (61 symptomatic sides). The mean age was 29 years (±6) and 70% were soccer players. Inter-examiner reliability was slight to moderate for adductor palpation (Cohen's Kappa statistic(κ)) = 0.02-0.54) and pubic palpation (κ = 0.37-0.45); moderate for the adductor stretch test (κ = 0.50), and fair to substantial for adductor resistance tests (κ = 0.22-0.74). Palpation pain was most prevalent at the adductor longus origin (94%) in athletes classified with adductor-related groin pain. CONCLUSION: The inter-examiner reliability of palpation tests varied from slight to moderate. The adductor stretch test had a moderate reliability, and adductor resistance tests a fair to substantial reliability. Adductor longus origin is the main site for palpation pain. Adductor palpation tests not related to the adductor longus have limited inter-examiner reliability. The adductor stretch test did not assist in classifying adductor-related groin pain.