Label-free detection of single nanoparticles with disordered nanoisland surface plasmon sensor.

We report sensing of single nanoparticles using disordered metallic nanoisland substrates supporting surface plasmon polaritons (SPPs). Speckle patterns arising from leakage radiation of elastically scattered SPPs provide a unique fingerprint of the scattering microstructure at the sensor surface. Experimental measurements of the speckle decorrelation are presented and shown to enable detection of sorption of individual gold nanoparticles and polystyrene beads. Our approach is verified through bright-field and fluorescence imaging of particles adhering to the nanoisland substrate.

Feasibility of using ring-mounted Halcyon Linac for single-isocenter/two-lesion lung stereotactic body radiation therapy.

PURPOSE: To demonstrate the plan quality and delivery efficiency of volumetric-modulated arc therapy (VMAT) with the Halcyon Linac ring delivery system (RDS) in the treatment of single-isocenter/two-lesion lung stereotactic body radiation therapy (SBRT). MATERIALS/METHODS: Sixteen previously treated non-coplanar VMAT single-isocenter/two-lesion lung SBRT plans delivered with SBRT-dedicated C-arm TrueBeam Linac were selected. Prescribed dose was 50 Gy to each lesion over five fractions with treatment delivery every other day and AcurosXB algorithm as the final dose calculation algorithm. TrueBeam single-isocenter plans were reoptimized for Halcyon Linac with coplanar geometry. Both TrueBeam and Halcyon plans were normalized for identical combined target coverage and evaluated. Conformity indices (CIs), heterogeneity index (HI), gradient index (GI), gradient distance (GD), and D2cm were compared. The normal lung V5Gy, V10Gy, V20Gy, mean lung dose (MLD), and dose to organs at risk (OAR) were evaluated. Treatment delivery parameters, including beam-on time, were recorded. RESULTS: Halcyon plans were statistically similar to clinically delivered TrueBeam plans. No statistical differences in target conformity, dose heterogeneity, or intermediate-dose spillage were observed (all, p > 0.05). Halcyon plans, on average, demonstrated statistically insignificant reduced maximum dose to most adjacent OAR and normal lung. However, Halcyon yielded statistically significant lower maximal dose to the ribs (p = 0.041) and heart (p = 0.026), dose to 1 cc of ribs (p = 0.035) and dose to 5 cc of esophagus (p = 0.043). Plan complexity slightly increased as seen in the average increase of total monitor units, modulation factor, and beam-on time by 480, 0.48, and 2.78 min, respectively. However, the estimated overall treatment time was reduced by 2.22 min, on average. Mean dose delivery accuracy of clinical TrueBeam plans and the corresponding Halcyon plans was 98.9 ± 0.85% (range: 98.1%-100%) and 98.45 ± 0.99% (range: 97.9%-100%), respectively, demonstrating similar treatment delivery accuracy. CONCLUSION: SBRT treatment of synchronous lung lesions via single-isocenter VMAT on Halcyon RDS is feasible and dosimetrically equivalent to clinically delivered TrueBeam plans. Halcyon provides excellent plan quality and shorter overall treatment time that may improve patient compliance, reduce intrafraction movement, improve clinic efficiency, and potentially offering lung SBRT treatments for underserved patients on a Halcyon only clinic.

SBRT treatment of abdominal and pelvic oligometastatic lymph nodes using ring-mounted Halcyon Linac.

PURPOSE/OBJECTIVES: This work seeks to evaluate the plan quality, treatment delivery efficiency, and accuracy of single-isocenter volumetric modulated arc therapy (VMAT) of abdominal/pelvic oligometastatic lymph nodes (LNs) stereotactic body radiation therapy (SBRT) on Halcyon Linac. MATERIALS AND METHODS: After completing the in-house multitarget end-to-end phantom testing and independent dose verification using MD Anderson's single-isocenter/multi-target (lung and spine target inserts) thorax phantom, eight patients with two to three abdominal/pelvic oligometastatic LNs underwent highly conformal single-isocenter VMAT-SBRT treatment using the Halcyon Linac 6MV flattening filter free (FFF) beam. Targets were identified using an Axumin PET/CT scan co-registered with planning CT images and a single-isocenter was placed between/among the targets. Doses between 25 and 36.25 Gy in 5 fractions were delivered. Patients were treated every other day. Plans were calculated in Eclipse with advanced AcurosXB algorithm for heterogeneity corrections. For comparison, Halcyon VMAT-SBRT plans were retrospectively generated for SBRT-dedicated TrueBeam with a 6MV-FFF beam using identical planning geometry and objectives. Target coverage, conformity index (CI), dose to 2 cm away from each target (D2cm) and dose to adjacent organs-at-risk (OAR) were evaluated. Additionally, various treatment delivery parameters including beam-on time were recorded. RESULTS: Phantom measurements showed acceptable spatial accuracy of conebeam CT-guided Halcyon SBRT treatments including compliance with MD Anderson's single-isocenter/multi-targets phantom credentialing results. For patients, the mean isocenter to tumor center distance was 3.4 ± 1.2 cm (range, 1.5-4.8 cm). The mean combined PTV was 18.9 ± 10.9 cc (range, 5.6-39.5 cc). There was no clinically significant difference in dose to LNs, CI, D2cm and maximal doses to OAR between single-isocenter Halcyon and Truebeam VMAT-SBRT plans, although, Halcyon plans provided preferably lower maximal dose to adjacent OAR. Additionally, total monitor units, beam-on time and overall treatment time was lower with Halcyon plans. Halcyon's portal dosimetry demonstrated a high pass rate of 98.1 ± 1.6% for clinical gamma passing criteria of 2%/2 mm. CONCLUSION: SBRT treatment of abdominal/pelvic oligometastatic LNs with single-isocenter VMAT on Halcyon was dosimetrically equivalent to TrueBeam. Faster treatment delivery to oligometastatic LNs via single-isocenter Halcyon VMAT can improve clinic workflow and patient compliance, potentially reducing intrafraction motion errors for well-suited patients. Clinical follow-up of these patients is ongoing.

Fast generation of lung SBRT plans with a knowledge-based planning model on ring-mounted Halcyon Linac.

PURPOSE: To demonstrate fast treatment planning feasibility of stereotactic body radiation therapy (SBRT) for centrally located lung tumors on Halcyon Linac via a previously validated knowledge-based planning (KBP) model to support offline adaptive radiotherapy. MATERIALS/METHODS: Twenty previously treated non-coplanar volumetric-modulated arc therapy (VMAT) lung SBRT plans (c-Truebeam) on SBRT-dedicated C-arm Truebeam Linac were selected. Patients received 50 Gy in five fractions. c-Truebeam plans were re-optimized for Halcyon manually (m-Halcyon) and with KBP model (k-Halcyon). Both m-Halcyon and k-Halcyon plans were normalized for identical or better target coverage than clinical c-Truebeam plans and compared for target conformity, dose heterogeneity, dose fall-off, and dose tolerances to the organs-at-risk (OAR). Treatment delivery parameters and planning times were evaluated. RESULTS: k-Halcyon plans were dosimetrically similar or better than m-Halcyon and c-Truebeam plans. k-Halcyon and m-Halcyon plan comparisons are presented with respect to c-Truebeam. Differences in conformity index were statistically insignificant in k-Halcyon and on average 0.02 higher (p = 0.04) in m-Halcyon plans. Gradient index was on average 0.43 (p = 0.006) lower and 0.27 (p = 0.02) higher for k-Halcyon and m-Halcyon, respectively. Maximal dose 2 cm away in any direction from target was statistically insignificant. k-Halcyon increased maximal target dose on average by 2.9 Gy (p < 0.001). Mean lung dose was on average reduced by 0.10 Gy (p = 0.004) in k-Halcyon and increased by 0.14 Gy (p < 0.001) in m-Halcyon plans. k-Halcyon plans lowered bronchial tree dose on average by 1.2 Gy. Beam-on-time (BOT) was increased by 2.85 and 1.67 min, on average for k-Halcyon and m-Halcyon, respectively. k-Halcyon plans were generated in under 30 min compared to estimated dedicated 180 ± 30 min for m-Halcyon or c-Truebeam plan. CONCLUSION: k-Halcyon plans were generated in under 30 min with excellent plan quality. This adaptable KBP model supports high-volume clinics in the expansion or transfer of lung SBRT patients to Halcyon.

The Phenotype of a Bone Marrow Transplant Nurse: Survival of the Fittest.

There is a need for proficient nursing practice in specialized critical care settings, such as a pediatric Bone Marrow Transplant (BMT) Unit. The staffing crisis continues to be problematic for areas around the country. Nursing tenure has been positively correlated with improving patient outcomes and confidence in giving care, so efforts must be made to retain pediatric BMT nurses. The purpose of this study was to investigate factors of resilience and how it pertains to the retention of pediatric BMT nurses through (1) Understanding current BMT nursing turnover and trend why nurses are leaving; (2) Measure resilience throughout BMT nursing cohort, covering all tenure of nurses; and (3) Interview senior nurses within the cohort to identify themes relating to retention and resilience using grounded theory methodology. This research was carried out in the Bone Marrow Transplant (BMT) Unit at Cincinnati Children's Hospital Medical Center (CCHMC). The study spanned from 2014 to 2019, during which researchers gathered extensive data to evaluate the turnover risk among BMT nurses. A detailed follow-up was conducted in 2019 to further assess this risk. To measure resilience levels, a group of 115 nurses in the unit completed the Connor Davidson Resilience Scale (CD-RISC). Additionally, in-depth interviews were conducted with 9 senior nurses in the cohort, continuing until theoretical saturation was reached, ensuring a comprehensive understanding of the factors influencing nurse turnover in the unit. Researchers looked retrospectively at nursing turnover from 2014 to 2019. Investigators determined the risk of new nurses leaving was between 22 and 24 months (HR 0.025). Further, follow-up was conducted for data points between 2019-present time, which showed a drastic change in the hazard rate curvature. However, the risk remained relatively the same at 22 to 24 months (HR 0.03). There was no statistical significance found between CD-RISC results and age (P = .465), gender (P = .725), working experience (P = .15), or education (P = .14). Through a constant comparative process, several themes were identified as positive, negative, and ambiguous contributions to the retention of nurses. The risk of nurses leaving after 2 years decreases significantly; therefore, we determined that a nurse with a commitment to pediatric BMT occurs with 2 years' experience. Although our initial hypothesis was that senior nurses had greater resilience than less tenured nurses, there was no statistical significance as the effect of resilience is small. However, we identified several additional factors pertinent to the pediatric BMT field which may be associated with nursing retention.

Interference of conically scattered light in surface plasmon resonance.

Surface plasmon polaritons on thin metal films are a well studied phenomena when excited using prism coupled geometries such as the Kretschmann attenuated total reflection configuration. Here we describe a novel interference pattern in the conically scattered light emanating from such a configuration when illuminated by a focused beam. We observe conditions indicating only self-interference of scattered surface plasmon polaritions without any contributions from specular reflection. The spatial evolution of this field is described in the context of Fourier optics and has applications in highly sensitive surface plasmon based biosensing.

Review of intra-articular local anaesthetic administration in horses: Clinical indications, cytotoxicity, and outcomes.

Equine practitioners frequently inject local anaesthetics (LA) intra-articularly in both diagnosis of lameness and for pain management intra- or post-operatively with synovial endoscopy. Recent reviews of the human and veterinary literature support the concept that chondrotoxicity of LA on joint tissues depends on the type of drug, dose administered, and duration of exposure. The purpose of this review is to summarise the current literature describing intra-articular local anaesthetic use, including both in vitro and in vivo studies, and to draw some comparisons to literature from other species where potential toxicity and duration of effect have been evaluated with the goal of advancing the field's understanding of intra-articular local anaesthetic use in horses, and indicating future directions for the field. The aggregate data available from all species, while generally sparse for horses, indicate that LA are rapidly cleared from the synovial fluid after injection, often within 30 min. In vitro data strongly suggest that lidocaine and bupivacaine are likely more chondrotoxic than other LA, although to what extent is still unknown, and cytotoxicity of LA may be mitigated through concurrent injection with HA, PRP, and drug combinations including nonsteroidal anti-inflammatories and opioids. The current body of in vitro research is not reflective of the in vivo environment, and further in vitro work, if performed, should focus on mimicking the native joint environment, utilising PK data and joint/injection volumes to replicate the native environment more accurately within the joint and the expected exposures to LA.

Erythrocyte removal from bone marrow aspirate concentrate improves efficacy as intra-articular cellular therapy in a rodent osteoarthritis model.

Background: Despite the high prevalence of osteoarthritis (OA), there remains a need for additional therapeutic options. Cellular therapies with minimally manipulated cells such as bone marrow aspirate concentrates (BMAC) are increasingly popular in the U.S. but clear-cut evidence of efficacy has not been established. In theory, BMAC injections provide a source of stromal cells to stimulate healing in OA and ligamentous injuries; however, BMAC injections are also often associated with inflammation, short-term pain, and mobility impairment. Given that blood is known to trigger inflammation in joints, we hypothesized that removing erythrocytes [red blood cells (RBCs)] from BMAC preparations prior to intra-articular injection would improve efficacy for OA treatment. Methods: To test this hypothesis, BMAC was collected from the bone marrow of mice. Three treatment groups were pursued: (I) untreated; (II) BMAC; or (III) BMAC depleted of RBCs by lysis. Product was injected into the femorotibial joint of mice 7 days after OA had been induced by destabilization of the medial meniscus (DMM). To assess the impact of treatment on joint function, individual cage monitoring (ANY-mazeTM) and Digigait treadmill-based analyses were performed over 4 weeks. At study completion, joint histopathology was assessed and immune transcriptomes within joint tissues were compared using a species-specific NanoString panel. Results: Significant improvements in activity, gait parameters, and histology scores were seen in animals receiving RBC-depleted BMAC compared to untreated mice; animals treated with non-depleted BMAC did not demonstrate this same extent of consistent significant improvement. Transcriptomic analysis of joint tissues revealed significant upregulation of key anti-inflammatory genes, including interleukin-1 receptor antagonist (IRAP), in mice treated with RBC-depleted BMAC compared to animals treated with non-RBC depleted BMAC. Conclusions: These findings indicate that RBC depletion in BMAC prior to intra-articular injection improves treatment efficacy and reduces joint inflammation compared to BMAC.

Double-vertebral segment SBRT via novel ring-mounted Halcyon Linac: Plan quality, delivery efficiency and accuracy.

To evaluate the plan quality, treatment delivery efficiency, and accuracy of single-isocenter/multi-target (SIMT) volumetric modulated arc therapy (VMAT) of double-vertebral segments stereotactic body radiation therapy (SBRT) on Halcyon ring delivery system (RDS). In-house multi-target end-to-end phantom testing and independent dose verification using the MD Anderson's single-isocenter/multi-target (lung/spine targets) thorax phantom were completed. Six previously treated patients with 2-vertebral segments on thoracic and/or lumber spine were replanned on Halcyon RDS with 6MV-FFF beam using a single-isocenter placed between the vertebral segments. Three full VMAT arcs with 0° and ±10° collimator angles and advanced Acuros-based dose engine for heterogeneity corrections were used. Prescription was 35 Gy in 5 fractions to each vertebral-segment, simultaneously. For comparison, Halcyon VMAT-SBRT plans were retrospectively created on SBRT-dedicated Truebeam with a 6MV-FFF beam using identical planning geometry and optimization objectives. Target coverage, conformity index (CI), heterogeneity index (HI), gradient index (GI), dose to 2-cm away from each target (D2-cm), and dose to adjacent organs-at-risk (OAR) were evaluated per NRG-BR002 protocol. Treatment delivery parameters were evaluated for both plans. In-house phantom measurements showed acceptable spatial accuracy (< 1mm within 5-cm from the isocenter) of conebeam CT-guided Halcyon SBRT treatments. The MD Anderson phantom irradiation credentialing results met IROC requirements for protocol patients. Mean isocenter-to-tumor center distance was 3.3 ± 0.6-cm (range 2.4 to 4.3-cm). Mean combined PTV was 57.3 ± 31.3 cc (range 20.1 to 99.9 cc). Both Halcyon and Truebeam SIMT-VMAT plans met NRG-BR002 compliance criteria and show similar CI, HI, GI, D2-cm. Maximal and volumetric doses to adjacent OAR including dose to partial spinal cord were lower with Halcyon RDS. Average total monitor units, modulation, and overall treatment time were lower with Halcyon plans by 130 MU, 0.2, 3.8 min, respectively, with similar beam-on time. Average pre-treatment patient-specific portal-dosimetry QA results on Halcyon showed a high pass rate of 99.6%, compared to SBRT-dedicated Truebeam pass rate of 96.8%, for 2%/2 mm clinical gamma passing criteria, suggesting more accurate treatment delivery on Halcyon RDS. SBRT treatment of double-vertebral segments via SIMT-VMAT plans on Halcyon for selected patients is feasible and dosimetrically superior to Truebeam Linac. Faster treatment delivery (<10 min) of double-vertebral segment SBRT on Halcyon could reduce patient intolerance due to severe back pain, potentially reduce intra-fraction motion errors, and improve patient throughput, and clinic workflow.

Probing biomechanical properties with a centrifugal force quartz crystal microbalance.

Application of force on biomolecules has been instrumental in understanding biofunctional behaviour from single molecules to complex collections of cells. Current approaches, for example, those based on atomic force microscopy or magnetic or optical tweezers, are powerful but limited in their applicability as integrated biosensors. Here we describe a new force-based biosensing technique based on the quartz crystal microbalance. By applying centrifugal forces to a sample, we show it is possible to repeatedly and non-destructively interrogate its mechanical properties in situ and in real time. We employ this platform for the studies of micron-sized particles, viscoelastic monolayers of DNA and particles tethered to the quartz crystal microbalance surface by DNA. Our results indicate that, for certain types of samples on quartz crystal balances, application of centrifugal force both enhances sensitivity and reveals additional mechanical and viscoelastic properties.