Background and purpose

Identifying feeding arteries of intracranial AVMs is very important for preoperative evaluation. DSA remains the reference standard for diagnosis but is invasive. Our aim was to evaluate the diagnostic accuracy of vessel-encoded pseudocontinuous arterial spin-labeling in identifying feeding arteries of intracranial AVMs by using DSA as the criterion standard.

Materials and methods

Eighteen patients with AVMs were examined with vessel-encoded pseudocontinuous arterial spin-labeling and DSA. Three postlabeling delays (postlabeling delay = 1, 1.3, and 1.6 seconds) were applied in 6 patients, and a single postlabeling delay (1 second) was applied in the remainder. Perfusion-weighted images were decoded into individual vascular territories with standard and relative tagging efficiencies, respectively. The supply fraction of each feeding artery to the AVM was calculated. The within-subject ANOVA was applied to compare supply fractions acquired across 3 postlabeling delays. Receiver operating characteristic analysis curves were calculated to evaluate the diagnostic accuracy of vessel-encoded pseudocontinuous arterial spin-labeling for identifying the feeding arteries of AVMs.

Results

There were no significant differences in supply fractions of the 3 major arteries to AVMs acquired with 3 postlabeling delays (P > .05). For vessel-encoded pseudocontinuous arterial spin-labeling with standard labeling efficiencies, the area under the receiver operating characteristic analysis curve was 0.942. The optimal cutoff of the supply fraction for identifying feeding arteries was 15.17%, and the resulting sensitivity and specificity were 84.62% and 93.33%, respectively. For vessel-encoded pseudocontinuous arterial spin-labeling with relative labeling efficiencies, the area under the receiver operating characteristic analysis curve was 0.957. The optimal cutoff of the supply fraction was 11.73%, which yielded an 89.74% sensitivity and 93.33% specificity.

Conclusions

The contribution fraction of each feeding artery of the AVM can be reliably estimated by using vessel-encoded pseudocontinuous arterial spin-labeling. Vessel-encoded pseudocontinuous arterial spin-labeling with either standard or relative labeling efficiencies offers a high level of diagnostic accuracy compared with DSA for identifying feeding arteries.

Background Cholelithiasis affects an estimated 20 million people in the United States yearly; 20% of symptomatic patients will develop acute cholecystitis (AC). A recent single-center study estimating test characteristics of point-of-care ultrasonography (POCUS) for the detection of AC, as defined by gallstones plus sonographic Murphy's or pericholecystic fluid or gallbladder wall-thickening, resulted in a sensitivity and specificity of 87% (95% confidence interval [CI] 66-97) and 82% (95% CI 74-88), respectively. No prior studies have been conducted to estimate the test characteristics of POCUS for the purpose of excluding acute calculous cholecystitis. Objective To determine whether the finding of gallstones alone on POCUS has high sensitivity, high negative predictive value, and low negative likelihood ratio for the exclusion of AC. Methods We conducted an analysis using data from a prospective cross-sectional single-center study of POCUS test to estimate the test characteristics using a simplified definition of a positive test - the presence of gallstones alone. Clinical follow-up and pathology reports were used as the reference standard. Test characteristics were calculated and compared to the standard definition, gallstones plus one secondary finding. Results The overall prevalence of AC was 14% (23 pathology-confirmed cases of 164 included patients). The sensitivity of the simplified definition was 100% (95% CI 85.7-100), negative predictive value 100% (95% CI 92.2-100), and negative likelihood ratio was < 0.1, compared to a sensitivity of 87% (95% CI 66-97%), negative predictive value 97% (95% CI 93-99%), and negative likelihood ratio of 0.16 (95% CI 0.06-0.5). Conclusion Simplifying the definition of the test findings on POCUS to gallstones alone has excellent sensitivity and negative predictive value for the exclusion of AC. This finding, if broadly validated prospectively, confirms the practice of excluding acute calculous cholecystitis using POCUS in emergency department patients.

Background

This randomized, double-blinded, placebo-controlled study investigated the efficacy of patient-controlled regional analgesia using a sciatic perineural catheter in the popliteal fossa and a portable infusion pump for outpatients having moderately painful, lower extremity orthopedic surgery.

Methods

Preoperatively, patients (n = 30) received a sciatic nerve block and perineural catheter in the popliteal fossa. Postoperatively, patients were discharged with both oral opioids and a portable infusion pump delivering study solution (0.2% ropivacaine or 0.9% saline) via the catheter for 3 days. Investigators and patients were blinded to random group assignment. Daily end-points included pain scores, opioid use and side effects, sleep quality, and symptoms of catheter- or local anesthetic-related complications.

Results

Ropivacaine (n = 15) infusion significantly reduced pain compared with saline (n = 15) infusion ( < 0.001). For example, the average pain at rest (scale: 0-10) on postoperative day 1 (median, 25th -75th percentile) was 4.0 (3.5-5.5) for the saline group, versus 0.0 (0.0-0.0) for the ropivacaine group (P < 0.001). Oral opioid use and related side effects were significantly decreased in the ropivacaine group. For example, on postoperative day 1, median tablet consumption was 8.0 (5.0-10.0) and 0.0 (0.0-0.0) for the saline and ropivacaine groups, respectively (P < 0.001). Sleep disturbance scores were more than 10-fold greater for saline administration than for ropivacaine infusion (P < 0.001). Overall satisfaction was significantly greater in the ropivacaine group. Other than two inadvertent catheter dislodgements, no catheter- or local anesthetic-related complications occurred.

Conclusions

After moderately painful orthopedic surgery of the lower extremity, ropivacaine infusion using a portable mechanical pump and a popliteal sciatic perineural catheter at home decreased pain, opioid use and related side effects, sleep disturbances, and improved overall satisfaction.

Deaf, deafblind, and hard of hearing (DDBHH) individuals experience barriers to accessing cancer screening, including ineffective patient-physician communication when discussing screening recommendations. For other underserved communities, culturally and linguistically aligned community health navigators (CHNs) have been shown to improve cancer screening and care. A needs assessment study was conducted to identify barriers and gather recommendations for CHN training resources. A community-based participatory needs assessment was conducted from May 2022 to June 2022 using three focus groups. Eight were cancer survivors, six advocates/navigators, and three clinicians. All questions were semi-structured and covered screening barriers, observations or personal experiences, perceived usefulness of having a CHN to promote cancer screening adherence, and training resources that may be useful to American Sign Language (ASL)-proficient CHNs, who are also culturally and linguistically aligned. Out of 20 focus group participants, seven self-identified as persons of color. Data highlighted systemic, attitudinal, communication, and personal-level barriers as recurrent themes. The most frequently cited barrier was access to training that supports the role and competencies of CHNs, followed by cultural considerations, access to cancer guidelines in ASL, dialect diversity in sign language, and the health system itself. Unaddressed barriers can contribute to health disparities, such as lower preventive cancer screening rates amongst DDBHH individuals. The next step is to translate recommendations into actionable tasks for DDBHH CHN training programs. As a result, CHNs will be well-equipped to help DDBHH individuals navigate and overcome their unique barriers to cancer screening and healthcare access.

Experiments on fusion plasmas produce high-dimensional data time series with ever-increasing magnitude and velocity, but turn-around times for analysis of this data have not kept up. For example, many data analysis tasks are often performed in a manual, ad-hoc manner some time after an experiment. In this article, we introduce the Delta framework that facilitates near real-time streaming analysis of big and fast fusion data. By streaming measurement data from fusion experiments to a high-performance compute center, Delta allows computationally expensive data analysis tasks to be performed in between plasma pulses. This article describes the modular and expandable software architecture of Delta and presents performance benchmarks of individual components as well as of an example workflow. Focusing on a streaming analysis workflow where electron cyclotron emission imaging (ECEi) data is measured at KSTAR on the National Energy Research Scientific Computing Center's (NERSC's) supercomputer we routinely observe data transfer rates of about 4 Gigabit per second. In NERSC, a demanding turbulence analysis workflow effectively utilizes multiple nodes and graphical processing units and executes them in under 5 min. We further discuss how Delta uses modern database systems and container orchestration services to provide web-based real-time data visualization. For the case of ECEi data we demonstrate how data visualizations can be augmented with outputs from machine learning models. By providing session leaders and physics operators, results of higher-order data analysis using live visualizations may make more informed decisions on how to configure the machine for the next shot.

Background

The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K-AKT-mTOR) signalling pathway is aberrantly activated in several cancers. Notch signalling maintains cell proliferation, growth and metabolism in part by driving the PI3K pathway. Combining the mTOR inhibitor ridaforolimus with the Notch inhibitor MK-0752 may increase blockade of the PI3K pathway.

Methods

This phase I dose-escalation study (NCT01295632) aimed to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of combination oral ridaforolimus (rising doses starting at 20 mg, 5 days/week) and oral MK-0752 (1800 mg once weekly) in patients with solid tumours. No intrapatient dose escalation was permitted.

Results

Twenty eight patients were treated on study. Ridaforolimus doses were escalated from 20 to 30 mg/day. Among 14 evaluable patients receiving ridaforolimus 20 mg, one DLT (grade 2 stomatitis, second episode) was reported. Among eight evaluable patients receiving ridaforolimus 30 mg, three DLTs were reported (one each grade 3 stomatitis, grade 3 diarrhoea, and grade 3 asthenia). The MTD was 20 mg daily ridaforolimus 5 days/week+1800 mg weekly MK-0752. The most common drug-related adverse events included stomatitis, diarrhoea, decreased appetite, hyperglycaemia, thrombocytopenia, asthenia and rash. Two of 15 (13%) patients with head and neck squamous cell carcinoma (HNSCC) had responses: one with complete response and one with partial response. In addition, one patient experienced stable disease ⩾6 months.

Conclusions

Combined ridaforolimus and MK-0752 showed activity in HNSCC. However, a high number of adverse events were reported at the MTD, which would require careful management during future clinical development.

We present analysis of more than 100 large-amplitude bipolar electrostatic structures in a quasi-perpendicular supercritical Earth's bow shock crossing, measured by the Magnetospheric Multiscale spacecraft. The occurrence of the bipolar structures is shown to be tightly correlated with magnetic field gradients in the shock transition region. The bipolar structures have negative electrostatic potentials and spatial scales of a few Debye lengths. The bipolar structures propagate highly oblique to the shock normal with velocities (in the plasma rest frame) of the order of the ion-acoustic velocity. We argue that the bipolar structures are ion phase space holes produced by the two-stream instability between incoming and reflected ions. This is the first identification of the ion two-stream instability in collisionless shocks.

Long-chain fatty acid oxidation disorders (LC-FAOD) can cause cardiac hypertrophy and cardiomyopathy, often presenting in infancy, typically leading to death or heart transplant despite ongoing treatment. Previous data on triheptanoin treatment of cardiomyopathy in LC-FAOD suggested a clinical benefit on heart function during acute failure. An additional series of LC-FAOD patients with critical emergencies associated with cardiomyopathy was treated with triheptanoin under emergency treatment or compassionate use protocols. Case reports from 10 patients (8 infants) with moderate or severe cardiomyopathy associated with LC-FAOD are summarized. The majority of these patients were detected by newborn screening, with follow up confirmatory testing, including mutation analysis; all patients were managed with standard treatment, including medium chain triglyceride (MCT) oil. While on this regimen, they presented with acute heart failure requiring hospitalization and cardiac support (ventilation, ECMO, vasopressors) and, in some cases, resuscitation. The patients discontinued MCT oil and began treatment with triheptanoin, an investigational drug. Triheptanoin is expected to provide anaplerotic metabolites, to replace deficient TCA cycle intermediates and improve effective energy metabolism. Cardiac function was measured by echocardiography and ejection fraction (EF) was assessed. EF was moderately to severely impaired prior to triheptanoin treatment, ranging from 12-45%. Improvements in EF began between 2 and 21days following initiation of triheptanoin, and peaked at 33-71%, with 9 of 10 patients achieving EF in the normal range. Continued treatment was associated with longer-term stabilization of clinical signs of cardiomyopathy. The most common adverse event observed was gastrointestinal distress. Of the 10 patients, 7 have continued on treatment, 1 elected to discontinue due to tolerability issues, and 2 patients died from other causes. Two of the case histories illustrate that cardiomyopathy may also develop later in childhood and/or persist into adulthood. Overall, the presented cases suggest a therapeutic effect of triheptanoin in the management of acute cardiomyopathy associated with LC-FAOD.

The global nature of the ITER project along with its projected approximately petabyte-per-day data generation presents not only a unique challenge but also an opportunity for the fusion community to rethink, optimize, and enhance our scientific discovery process. Recognizing this, collaborative research with computational scientists was undertaken over the past several years to create a framework for large-scale data movement across wide-area networks to enable global near-real-time analysis of fusion data. This would broaden the available computational resources for analysis/simulation and increase the number of researchers actively participating in experiments. An official demonstration of this framework for fast, large data transfer and real-time analysis was carried out between the KSTAR tokamak in Daejeon, Korea, and Princeton Plasma Physics Laboratory (PPPL) in Princeton, New Jersey. Streaming large data transfer, with near-real-time movie creation and analysis of the KSTAR electron cyclotron emission imaging data, was performed using the Adaptable Input Output (I/O) System (ADIOS) framework, and comparisons were made at PPPL with simulation results from the XGC1 code. These demonstrations were made possible utilizing an optimized network configuration at PPPL, which achieved over 8.8 Gbps (88% utilization) in throughput tests from the National Fusion Research Institute to PPPL. This demonstration showed the feasibility for large-scale data analysis of KSTAR data and provides a nascent framework to enable use of globally distributed computational and personnel resources in pursuit of scientific knowledge from the ITER experiment.