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This study aimed to develop and evaluate a costeffective Inertial Measurement Unit (IMU) system for gait analysis, comparing its performance with the Vicon system and the VideoPose3D algorithm. The system comprises five calibrated sensors and a mobile app to measure lower body orientation during gait and stair climbing. Eight healthy participants were involved in the experiment, each performing ten repetitions to analyze hip and knee flexion angles. The IMU system demonstrated significantly lower mean square error than deep learning-based approaches and comparable results to the Vicon system, indicating its potential for clinical and research applications.

Wound healing can be delayed if the biomechanical stability of the wound closure is inadequate. Therefore, it is necessary to investigate different suturing techniques for their biomechanical stability. In this study, suturing techniques suitable for the forehead area were investigated. For this application, a special test setup was developed to simulate the curvature of the forehead and the corresponding physiological configuration. The average forehead curvature is 62.24 ± 4.11 mm in radius. To simulate this curvature, the skin specimens are subjected to tensile stress over the spherical surface using a standard uniaxial testing machine. For the evaluation, an automated evaluation tool for MATLAB was also developed. Three different suturing techniques (Straight, Lazy-S, Zigzag) were investigated and tested for their biomechanical stability. Of the three suturing techniques, the Zigzag suture proved to be the most stable with the highest stiffness of 44.23 ± 8.18 % and the highest final failure of 32.60 ± 4.95 % (relative to the control sample without incision). The study has shown that the test setup can be used to investigate different forehead suture techniques.

Ewing sarcomas are malignant neoplasm entities typically found in children and adolescents. Early detection is crucial for therapy and prognosis. Due to the low incidence the general experience as well as according data is limited. Novel support tools for diagnosis, such as deep learning models for image interpretation, are required. While acquiring sufficient data is a common obstacle in medicine, several techniques to tackle small data sets have emerged. The general necessity of large data sets in addition to a rare disease lead to the question whether transfer learning can solve the issue of limited data and subsequently support tasks such as distinguishing Ewing sarcoma from its main differential diagnosis (acute osteomyelitis) in paediatric radiographs. 42,608 unstructured radiographs from our musculoskeletal tumour centre were retrieved from the PACS. The images were clustered with a DeepCluster, a self-supervised algorithm. 1000 clusters were used for the upstream task (pretraining). Following, the pretrained classification network was applied for the downstream task of differentiating Ewing sarcoma and acute osteomyelitis. An untrained network achieved an accuracy of 81.5%/54.2%, while an ImageNet-pretrained network resulted in 89.6%/70.8% for validation and testing, respectively. Our transfer learning approach surpassed the best result by 4.4%/17.3% percentage points. Transfer learning demonstrated to be a powerful technique to support image interpretation tasks. Even for small data sets, the impact can be significant. However, transfer learning is not a final solution to small data sets. To achieve clinically relevant results, a structured and systematic data acquisition is of paramount importance.

Introduction: Osteosynthesis of the equine femur is still a challenge for veterinary medicine. Even though intramedullary fracture fixation is possible nowadays, the varying geometry of the medullary cavity along the bone axis is a critical factor. Limited contact area between implant and bone can cause insufficient primary stability. In this study, it was investigated whether the osteosynthesis stability can be improved with a form-adaptive reinforcement for the diaphyseal part of the proximal fragment. Material and Methods: Eight equine femora were fitted with intramedullary nail osteosynthesis and analyzed by 4-point bending. Virtual position planning of the ex-vivo implantation using CT-data increased comparability. For five femora the proximal fragment was reinforced with a flexible polymer mixture. Longterm stability was tested via cyclic loading. Bending stiffness and its development due to cyclic loading was evaluated before and after reinforcement procedure. Finally, load-to-failure was tested in the same setup. Results and Discussion: The application of the polymer reinforcement increased the maximum torque in the load-tofailure measurement by 26%. Bending stiffness was not affected in the measured loading range by the reinforcement. Cyclic loading increased bending stiffness for a conditioned state but showed to be reversible for the most part. Conclusion: The fracture adjacent reinforcement showed to be beneficial to the osteosynthesis stability, but further investigation is necessary for surgical application.

For the development of new types of hip implants for acetabulum revision, it is beneficial to analyse the acetabular defects of the indication group in advance. In order to be able to specially compare the bone defects with each other, a normalisation and accompanying scaling of the pelvis is necessary. Uniform scaling is required so that the bone structures are not distorted. In the following study, three scaling methods based on the minimal bounding box and sphere principle are compared with a method using 14 landmarks on the pelvis.The landmark method is applied to determine the true scaling factor. For the comparison of the different methods, 40 female pelvic models with an acetabular defect are analysed. In the comparison of the scaling methods, the method using minimal bounding spheres shows the least deviation from the landmark method (mean difference 3.30 ± 2.17 %). Due to the fact that no preprocessing (definition of the landmarks) is required and the fast implementation of the algorithm, the minimal bounding sphere is to be preferred to the landmark method for a fast size estimation.

UKM Kartifarm Jaya Abadi dengan produk kopi bubuk merk Liber.Co dalam proses pengembangan usahanya mengalami beberapa kendala terkait standar mutu, kemasan, perizinan, sertifikasi produk, serta pasokan produk yang akan dijual. Kualitas adalah aspek terpenting dari pemasaran kopi, salah satunya adalah kualitas fisik dan visual kopi. Pada penelitian ini dilakukan karakterisasi mutu fisik kopi bubuk Liber.Co untuk mengetahui kesesuaiannya dengan SNI 01-3542-2004 Syarat Mutu Kopi Bubuk. Hasil menunjukkan kopi bubuk liberika Sambas yang diproduksi CV. KartiFarm Jaya Abadi dengan merk Liber.Co memiliki karakteristik mutu fisik kopi bubuk yang sesuai dengan persyaratan SNI 01-3542-2004: Kopi Bubuk. Mutu fisik berupa keadaan bau atau aroma, warna, dan rasa kopi bubuk liberika Sambas menunjukkan keadaan normal.

Bioreactors with a controlled physiological environment are being developed to study various cell processes. The influences of mechanostimulation on bone cell cultures can be investigated using a compression bioreactor. The developed bioreactor system applies a cyclic compression force to the specimen via an eccentrically mounted push rod. The compression force is monitored by a force sensor to detect changes in the material properties of the specimen. Depending on the piston setting, a stroke of 0.28 - 2.50 mm can be applied to the specimen. The bioreactor system was tested with a trial run of 18 days. A sample was continuously stimulated with a loading frequency of 2 Hz and a stroke of 1.50 mm. The sterility in the cell chamber as well as the functionality of the realised bioreactor stimulation system could be successfully confirmed

Penelitianinimembahastentangekstraksi akumulasi voting pada accumulatorarray yang dihasilkan algoritma InvariantGeneralised Hough Transform (GHT) untukmenemukan posisi kemunculan motif pada citrabatik yang telah mengalami perubahan skaladan atau rotasi. Proses ekstraksi accumulatorarray dilakukan dengan 4 (empat) metode yaituHillClimbingClustering,KombinasiTresholding dan Density Based SpatialClustering of Application with Noise (DBSCAN),Kombinasi Hill Climbing dan DBSCAN sertaKombinasi Tresholding, Hill Climbing danDBSCAN. Untuk setiap metode yang diusulkan,dihitung nilai Precision dan Recall. Precisiondan Recall tertinggi diperoleh oleh KombinasiTresholding, Hill Climbing dan DBSCAN, yaitusebesar 23% untuk precision dan 35% untukrecall.

Penelitian ini memanfaatkan silika dalam bentuk gel dari hasil pemurnian abu sekam sebagai adsorber air pada papan partikel dengan komposisi silika gel di dalam campuran 0%, 5%, 10% dan 15%. Karakterisasi yang dilakukan meliputi meliputi pengujian: kerapatan, kadar air, pengembangan tebal, modulus patah, MOR dan keteguhan rekat internal,IB. Berdasarkan hasil pengujian papan partikel maka disimpulkan bahwa kadar silika optimum yang diperoleh dari penelitian adalah sebesar 5% dan berdasarkan analisis ekstrapolasi nilai hasil pengujian komposisi silika gel yang sebaiknya ditambahkan adalah 4,13%.

We report on the construction and performance of a home-built viscometer employing a quartz tuning fork resonator as the sensing element. The resulting device allows measuring the viscosity of fluids in volumes as low as 300 μl, while controlling the temperature between -120 °C and 150 °C. For non-conducting fluids, bare tuning forks can be used, reaching the accuracy of 1% or better in the whole temperature range. For weakly conducting fluids such as aqueous solutions, an insulating coating of paint is applied, resulting in reduced sensitivity and accuracy. The capabilities and limitations of the viscometer are illustrated on the viscosity measurements of n-hexane (between -90 °C and +50 °C) and water (between 10 °C and 90 °C). Improvements regarding performance in conducting liquids and temperature stabilization are discussed.

Objectives: The aim of the study is to determine if law enforcement officers develop subclinical atherosclerotic cardiovascular disease (ASCVD) earlier than nonofficers and, if so, the extent to which conventional risk factors explain this difference. Methods: Estimated pulse wave velocity (ePWV) was the marker of subclinical ASCVD. EPWV, ASCVD risk factors, metabolic syndrome (MetS), and 10-year risk for ASCVD were compared among 408 law enforcement officers and a civilian cohort. Results: EPWV, 10-year ASCVD risk, and MetS prevalence increased significantly with age. All but the officers age 55 and older had higher ePWV cohort than the civilian cohort ( P < 0.001). Ten-year ASCVD risk explained the most variability of ePWV ( R2 = 0.49, P < 0.001). Conclusions: Officers develop subclinical ASCVD earlier than nonofficers. Conventional ASCVD risk factors only explain about half of this increase. Occupational factors may play a role in contributing to this increased ASCVD risk., Competing Interests: Conflict of interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Ultrafast science builds on dynamic compositions of precisely timed light pulses, and evolving groups of pulses are observed in almost every mode-locked laser. However, the underlying physics has rarely been controlled or used until now. Here, we demonstrate a general approach to control soliton motion inside a dual-comb laser and the programmable synthesis of ultrashort pulse patterns. Introducing single-pulse modulation inside an Er:fiber laser, we rapidly shift the timing between two temporally separated soliton combs. Their superposition outside the cavity yields ultrashort soliton sequences. On the basis of real-time spectral interferometry, we observe the deterministic switching of intersoliton separation arising from the interplay of attracting and repulsing forces via ultrafast nonlinearity and laser gain dynamics. Harnessing these insights, we demonstrate the high-speed all-optical synthesis of nano- to picosecond pump-probe delays and programmable free-form soliton trajectories. This concept may pave the way to a new class of all-optical delay generators for ultrafast measurements at unprecedented high tuning, cycling, and acquisition speeds.

Differential activation of the renin-angiotensin system (RAS) likely contributes to sex differences in cardiovascular outcomes in premenopausal women compared with age-matched men. Women demonstrate reduced activation of the vasoconstrictor angiotensin II type 1 receptors (AT 1 R) compared with men, and evidence suggests that women also likely have increased sensitivity of the vasodilatory angiotensin II type 2 receptors (AT 2 R). However, few in vivo studies have directly examined sex differences in AT 2 R-mediated dilation, or the balance between AT 1 R- and AT 2 R-mediated vascular responses in humans. Using the cutaneous microcirculation as a model, we hypothesized that AT 2 R-mediated dilation would be greater in premenopausal women compared with men, and that AT 1 R-blockade would augment AT 2 R-mediated dilation to a greater extent in men than in women. Twelve healthy women (22 ± 3 yr) and 12 men (23 ± 5 yr) had two intradermal microdialysis fibers placed in the ventral forearm for graded infusions of compound 21 (AT 2 R agonist; 10 -12 to 10 -8 M) in a control fiber site and a site treated with 43 µM losartan (AT 1 R antagonist). Red blood cell flux was measured continuously by laser-Doppler flowmetry, and cutaneous vascular conductance [CVC = flux/mean arterial pressure (MAP)] was normalized to maximum [%max; 28 mM sodium nitroprusside (SNP) + 43 °C]. Women had greater AT 2 R-mediated dilation compared with men (women: 25 ± 4 vs. men: 15 ± 2%max, P = 0.03). Local AT 1 R inhibition increased AT 2 R-mediated dilation in men (losartan: 26 ± 4 vs. control: 15 ± 2%max, P < 0.001) but had no effect in women (losartan: 27 ± 6 vs. control: 25 ± 4%max, P > 0.05). These data suggest that premenopausal women have a greater AT 2 R-mediated vasodilation response than men, and that AT 1 R activation inhibits AT 2 R-mediated dilation in men, but not in women. NEW & NOTEWORTHY Premenopausal women have greater protection against cardiovascular disease than age-matched men. However, the role of vasoconstrictor angiotensin II type 1 receptors (AT 1 R) and vasodilatory angiotensin II type 2 receptors (AT 2 R) in mediating these sex differences is unclear. Here, we demonstrate that women have greater AT 2 R-mediated vasodilation than men and that AT 1 R negates AT 2 R-mediated dilation in men, but not in women.

Background: Veterans suffer substantial morbidity and mortality from lung cancer. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce mortality. Guidelines recommend counseling and shared decision-making (SDM) to address the benefits and harms of screening and the importance of tobacco cessation before patients undergo screening., Observations: We implemented a centralized LCS program at the Iowa City Veterans Affairs Medical Center with a nurse program coordinator (NPC)-led telephone visit. Our multidisciplinary team ensured that veterans referred from primary care met eligibility criteria, that LDCT results were correctly coded by radiology, and that pulmonary promptly evaluated abnormal LDCT. The NPC mailed a decision aid to the veteran and scheduled a SDM telephone visit. We surveyed veterans after the visit using validated measures to assess knowledge, decisional conflict, and quality of decision making. We conducted 105 SDM visits, and 91 veterans agreed to LDCT. Overall, 84% of veterans reported no decisional conflict, and 59% reported high-quality decision making. While most veterans correctly answered questions about the harms of radiation, false-positive results, and overdiagnosis, few knew when to stop screening, and most overestimated the benefit of screening and the predictive value of an abnormal scan. Tobacco cessation interventions were offered to 72 currently smoking veterans., Conclusions: We successfully implemented an LCS program that provides SDM and tobacco cessation support using a centralized telehealth model. While veterans were confident about screening decisions, knowledge testing indicated important deficits, and many did not engage meaningfully in SDM. Clinicians should frame the decision as patient centered at the time of referral, highlight the importance of SDM, and be able to provide adequate decision support., Competing Interests: Author disclosures The study was supported by a grant from the Office of Rural Health (ORH) (NOMAD #03526) awarded to Richard Hoffman. The funding body did not play a role in the design of the study or the collection and analysis of data. Lisa Lowenstein and Robert Volk are supported by a grant funded by the National Institutes of Health, National Cancer Institute, USA, under award number P30CA016672, using the Shared Decision-Making Core, and by a grant from the Cancer Prevention and Research Institute of Texas (RP160674). None of the other authors have any disclosures. None of the authors have conflicts of interest with the work., (Copyright © 2023 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Introduction: Sleep apnea (SA) is highly prevalent in patients with chronic kidney disease and may contribute to the development and/or progression of this condition. Previous studies suggest that dysregulation of renal hemodynamics and oxygen flux may play a key role in this process. The present study sought to determine how chronic intermittent hypoxia (CIH) associated with SA affects regulation of renal artery blood flow (RBF), renal microcirculatory perfusion (RP), glomerular filtration rate (GFR), and cortical and medullary tissue PO 2 as well as expression of genes that could contribute to renal injury. We hypothesized that normoxic RBF and tissue PO 2 would be reduced after CIH, but that GFR would be increased relative to baseline, and that RBF, RP, and tissue PO 2 would be decreased to a greater extent in CIH vs. sham during exposure to intermittent asphyxia (IA, F i O 2 0.10/F i CO 2 0.03). Additionally, we hypothesized that gene programs promoting oxidative stress and fibrosis would be activated by CIH in renal tissue. Methods: All physiological variables were measured at baseline (F i O 2 0.21) and during exposure to 10 episodes of IA (excluding GFR). Results: GFR was higher in CIH-conditioned vs. sham ( p < 0.05), whereas normoxic RBF and renal tissue PO 2 were significantly lower in CIH vs. sham ( p < 0.05). Reductions in RBF, RP, and renal tissue PO 2 during IA occurred in both groups but to a greater extent in CIH ( p < 0.05). Pro-oxidative and pro-fibrotic gene programs were activated in renal tissue from CIH but not sham. Conclusion: CIH adversely affects renal hemodynamic regulation and oxygen flux during both normoxia and IA and results in changes in renal tissue gene expression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kious, Savage, Twohey, Highum, Philipose, Díaz, Del Rio, Lang, Clayton and Marcus.)

Background: 18F-flortaucipir PET received FDA approval to visualize aggregated neurofibrillary tangles (NFTs) in brains of adult patients with cognitive impairment being evaluated for Alzheimer's disease (AD). However, manufacturer's guidelines for visual interpretation of 18F-flortaucipir PET differ from how 18F-flortaucipir PET has been measured in research settings using standardized uptake value ratios (SUVRs). How visual interpretation relates to 18F-flortaucipir PET SUVR, cerebrospinal fluid (CSF) biomarkers, or longitudinal clinical assessment is not well understood., Objective: We compare various diagnostic methods in participants enrolled in longitudinal observational studies of aging and memory (n = 189, 23 were cognitively impaired)., Methods: Participants had tau PET, Aβ PET, MRI, and clinical and cognitive evaluation within 18 months (n = 189); the majority (n = 144) also underwent lumbar puncture. Two radiologists followed manufacturer's guidelines for 18F-flortaucipir PET visual interpretation., Results: Visual interpretation had high agreement with SUVR (98.4%)and moderate agreement with CSF p-tau181 (86.1%). Two participants demonstrated 18F-flortaucipir uptake from meningiomas. Visual interpretation could not predict follow-up clinical assessment in 9.52% of cases., Conclusion: Visual interpretation was highly consistent with SUVR (discordant participants had hemorrhagic infarcts or occipital-predominant AD NFT deposition) and moderately consistent with CSF p-tau181 (discordant participants had AD pathophysiology not detectable on tau PET). However, close association between AD NFT deposition and clinical onset in group-level studies does not necessarily hold at the individual level, with discrepancies arising from atypical AD, vascular dementia, or frontotemporal dementia. A better understanding of relationships across imaging, CSF biomarkers, and clinical assessment is needed to provide appropriate diagnoses for these individuals.

Objective: Reproducibility of the reflex cutaneous vasoconstriction response is currently unknown. Our aim was to determine the test-retest reproducibility of laser speckle contrast imaging (LSCI) and varying sampling depths of laser Doppler flowmetry (LDF) in response to whole-body cooling., Methods: Over two studies, nine and fourteen healthy, young adults underwent a 40-min cooling bout over two separate experiments. Participants were cooled from 34.0 °C to 30.5 °C and held at a 30.5 °C plateau for 10-min prior to rewarming. Throughout the cooling bout, changes in blood flow were measured as LSCI flux and LDF flux for Study 1 and LDF flux by three different LDF sampling depths in Study 2. Test-retest reproducibility and reliability were evaluated by the coefficient of variation (CV) and intraclass correlation coefficients (ICC), respectively. Vasoconstriction was presented as cutaneous vascular conductance (CVC = flux / mean arterial pressure) and expressed as a percent change from baseline (%ΔCVC BASELINE )., Results: For Study 1, test-retest reproducibility displayed good reproducibility for LSCI (CV: <9.0%) and good-to-moderate for LDF (CV: <17.0%) throughout the cooling bout and at plateau (LSCI CV: 1.0%; LDF CV: 1.9%). For Study 2, all Doppler depths displayed good reproducibility during the cooling bout (CV: <9.0%) and at plateau (CV: 0.9-2.0%). Only LSCI demonstrated reliability across both studies (ICC: 0.58-0.88). A reduced vasoconstriction response was measured with the shallowest penetration in the skin (LSCI: 26 ± 0.9%ΔCVC BASELINE ) compared to the Doppler with the deepest penetration (35 ± 0.6%ΔCVC BASELINE , p < 0.001)., Conclusions: Although Dopplers better discriminate the reflex cutaneous vasoconstriction response, LSCI exhibits greater test-retest reproducibility and reliability, and thus may be more suitable for longitudinal assessments., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Remote ischaemic preconditioning (RIPC), induced by intermittent periods of limb ischaemia and reperfusion, confers cardiac and vascular protection from subsequent ischaemia-reperfusion (IR) injury. Early animal studies reliably demonstrate that RIPC attenuated infarct size and preserved cardiac tissue. However, translating these adaptations to clinical practice in humans has been challenging. Large clinical studies have found inconsistent results with respect to RIPC eliciting IR injury protection or improving clinical outcomes. Follow-up studies have implicated several factors that potentially affect the efficacy of RIPC in humans such as age, fitness, frequency, disease state and interactions with medications. Thus, realizing the clinical potential for RIPC may require a human experimental model where confounding factors are more effectively controlled and underlying mechanisms can be further elucidated. In this review, we highlight recent experimental findings in the peripheral circulation that have added valuable insight on the mechanisms and clinical benefit of RIPC in humans. Central to this discussion is the critical role of timing (i.e. immediate vs. delayed effects following a single bout of RIPC) and the frequency of RIPC. Limited evidence in humans has demonstrated that repeated bouts of RIPC over several days uniquely improves vascular function beyond that observed with a single bout alone. Since changes in resistance vessel and microvascular function often precede symptoms and diagnosis of cardiovascular disease, repeated bouts of RIPC may be promising as a preclinical intervention to prevent or delay cardiovascular disease progression., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The optimal frequency and duration of remote ischemic preconditioning (RIPC) that augments microvascular function is unknown. A single bout of RIPC increases cutaneous endothelial function for ∼48 h, whereas 1 week of daily RIPC bouts improves more sustained endothelium-independent function. We hypothesized that 3 days of RIPC separated by rest days (3QOD RIPC) would result in sustained increases in both endothelium-dependent and endothelium-independent functions. Cutaneous microvascular function was assessed in 13 healthy young participants (aged 20.5 ± 3.9 years; 5 males, 8 females) before 3QOD and then 24, 48, and 72 h and a week after 3QOD. RIPC consisted of four repetitions of 5 min of blood flow occlusion separated by 5 min of reperfusion. Skin blood flow responses to local heating ( T loc = 42°C), acetylcholine (Ach), and sodium nitroprusside (SNP) were measured using laser speckle contrast imaging and expressed as cutaneous vascular conductance (CVC = PU⋅mmHg -1 ). Local heating-mediated vasodilation was increased 72 h after 3QOD and the increased responsivity persisted a week later (1.08 ± 0.24 vs. 1.34 ± 0.46, 1.21 ± 0.36 PU⋅mmHg -1 ; ΔCVC, pre-RIPC vs. 72 h, a week after 3QOD; P = 0.054). Ach-induced cutaneous vasodilation increased a week after 3QOD (0.73 ± 0.41 vs. 0.95 ± 0.49 PU⋅mmHg -1 ; ΔCVC, pre-RIPC vs. a week after 3QOD; P < 0.05). SNP-induced cutaneous vasodilation increased 24 h after 3QOD (0.47 ± 0.28 vs. 0.63 ± 0.35 PU⋅mmHg -1 ; ΔCVC, pre-RIPC vs. 24 h; P < 0.05), but this change did not persist thereafter. Thus, 3QOD induced sustained improvement in endothelium-dependent vasodilation but was not sufficient to sustain increases in endothelium-independent vasodilation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Franke and Lang.)

Rationale and Objectives: Pulmonary CTA is the current standard method to assess for suspected pulmonary embolism. In some instances, the test results in low confidence interpretations. Our purpose was to compare the diagnostic confidence for three different scan protocols., Materials and Methods: Pulmonary CTA images from 401 patients were retrospectively analyzed. 202 studies used a tube voltage of 120 kVp and a contrast injection rate of 4 cc/s, 99 studies 120 kVp and 5 cc/s, and 100 studies 100 kVp and 4 cc/s. The level of diagnostic confidence was extracted from the final clinical reports. For each study, attenuation of the pulmonary artery, image noise, signal-to-noise ratio (SNR), and radiation dose were compared., Results: The 120 kVp, 5 cc/s protocol resulted in high diagnostic confidence in 84% of cases, more than with the 120 kVp, 4cc/s (65%) and the 100 kVp protocol (65%, p < 0.004). The 100 kVp protocol had a lower radiation dose, higher image noise, lower SNR, but equal and higher attenuation values of the pulmonary artery., Conclusion: The reduction of tube voltage to 100 kVp at 4 cc/s maintains diagnostic confidence with lower radiation exposure, but does not equal the higher confidence achieved with 120 kVp at 5cc/s., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Microscopic electric fields govern the majority of elementary excitations in condensed matter and drive electronics at frequencies approaching the Terahertz (THz) regime. However, only few imaging schemes are able to resolve sub-wavelength fields in the THz range, such as scanning-probe techniques, electro-optic sampling, and ultrafast electron microscopy. Still, intrinsic constraints on sample geometry, acquisition speed and field strength limit their applicability. Here, we harness the quantum-confined Stark-effect to encode ultrafast electric near-fields into colloidal quantum dot luminescence. Our approach, termed Quantum-probe Field Microscopy (QFIM), combines far-field imaging of visible photons with phase-resolved sampling of electric waveforms. By capturing ultrafast movies, we spatio-temporally resolve a Terahertz resonance inside a bowtie antenna and unveil the propagation of a Terahertz waveguide excitation deeply in the sub-wavelength regime. The demonstrated QFIM approach is compatible with strong-field excitation and sub-micrometer resolution-introducing a direct route towards ultrafast field imaging of complex nanodevices in-operando., (© 2022. The Author(s).)

Fluorodeoxyglucose (FDG) PET/CT is a vital imaging technique used for staging, assessing treatment response, and restaging following completion of therapy in patients who are undergoing or have completed oncologic treatment. A variety of adverse effects from chemotherapy, targeted therapy, immunotherapy, and radiation therapy are commonly encountered in oncologic patients. It is important to be aware of the manifestations of these adverse effects seen on FDG PET/CT images to avoid misinterpreting these findings as disease progression. Furthermore, early identification of these complications is important, as it may significantly affect patient management and even lead to a change in treatment strategy. The authors focus on the FDG PET/CT manifestations of a broad spectrum of oncologic therapy-related adverse effects in the thorax, as well as some treatment-related changes that may potentially mimic malignancy. Online supplemental material is available for this article. © RSNA, 2021.

Lung scintigraphy, or ventilation-perfusion (V/Q) scan, is one of the commonly performed studies in nuclear medicine. Owing to variability in clinical applications and different departmental workflows, many trainees are not comfortable interpreting the results of this study. This article provides a simplified overview of V/Q imaging, including a review of its technique, interpretation methods, and established and emerging clinical applications. The authors review the role of V/Q imaging in evaluation of acute and chronic pulmonary embolism, including the role of SPECT/CT and comparing V/Q scan with CT angiography. In addition, a variety of other applications of pulmonary scintigraphy are discussed, including congenital heart disease, pretreatment planning for lung cancer and emphysema, posttransplant imaging for bronchiolitis obliterans, and less common vascular and nonvascular pathologic conditions that may be detected with V/Q scan. This article will help radiologists and residents interpret the results of V/Q scans and understand the various potential clinical applications of this study. Online supplemental material is available for this article. © RSNA, 2021.

New Findings: What is the central question of this study? Animal infarct studies indicate a delayed window of cardiac protection after remote ischaemic preconditioning (RIPC); however, the presence and duration of this delayed effect have not been examined in human microvasculature in vivo. What is the main finding and its importance? Cutaneous vasodilatation induced by local heating or ACh was increased significantly 24 and 48 h after a single bout of RIPC, respectively. Neither response persisted beyond ∼48 h. Sodium nitroprusside-induced cutaneous vasodilatation was not altered. These findings reveal a delayed increase in microvascular endothelial function after a single bout of RIPC., Abstract: Remote ischaemic preconditioning (RIPC) induces protective effects from ischaemia-reperfusion injury. In the myocardium and conduit vasculature, a single bout of RIPC confers delayed protection that begins 24 h afterwards and lasts for 2-3 days. However, the extent and the time line in which a single bout of RIPC affects the human microvasculature are unclear. We hypothesized that a single bout of RIPC results in a delayed increase in skin microvascular function. Sixteen healthy participants (age, 23 ± 4 years; seven males, nine females; MAP, 82 ± 7 mmHg) were recruited to measure cutaneous microvascular function immediately before a single bout of RIPC and 24, 48 and 72 h and 1 week after the bout. The RIPC consisted of four repetitions of 5 min of arm blood flow occlusion interspersed by 5 min reperfusion. Skin blood flow responses to local heating (local temperature of 42°C), ACh and sodium nitroprusside were measured by laser speckle contrast imaging and expressed as the cutaneous vascular conductance (CVC; in perfusion units per millimetre of mercury). Vasodilatation in response to local heating was increased 24 and 48 h after RIPC (ΔCVC, 1.05 ± 0.07 vs. 1.18 ± 0.07 and 1.24 ± 0.08 PU mmHg -1 , pre- vs. 24 and 48 h post-RIPC; P < 0.05). Acetylcholine-induced cutaneous vasodilatation increased significantly 48 h after RIPC (ΔCVC, 0.71 ± 0.07 vs. 0.93 ± 0.12 PU mmHg -1 , pre- vs. 48 h post-RIPC; P < 0.05) and returned to baseline thereafter. Sodium nitroprusside-mediated vasodilatation did not change. Thus, a single bout of RIPC elicited a delayed response in the microvasculature, resulting in an improvement in the endothelium-dependent cutaneous vasodilatory response that peaked ∼48 h post-RIPC., (© 2021 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Ecosystem engineers modify habitats through processes other than trophic interactions, such as by regulating soil nutrients, and can influence resource availability and quality for other organisms. Predator-mediated elemental cycling may be especially important in determining plant diversity and growth in ecosystems where soil fertility and primary productivity are low. Red foxes (Vulpes vulpes L.), top predators in the Subarctic, could engineer local ecosystems through denning, which could create biogeochemical hotspots of nutrients due to continual input of feces, urine and prey remains. We examined soil and vegetation characteristics on red fox dens and paired control sites in woodland habitats near the Arctic treeline in Manitoba, Canada. The organic soil layer on den sites had 81% more inorganic nitrogen and 250% more extractable phosphorus than in control areas. Denning also increased soil respiration and pH in the organic layer, suggesting improved soil quality and nutrient availability for plants. By enriching nutrients and disturbing soils through digging, den sites had a higher plant species ß-diversity and a greater cover of erect woody shrubs (Salix spp.), grasses (Leymus mollis (Trinius) Pilger) and weedy ephemerals compared to control sites, resulting in a regional increase in plant species richness. Our research highlights the importance of considering impacts of predators other than through their consumption of prey, and provides insight into the role of red foxes in modifying plant diversity and productivity in the Subarctic.

Background: Impaired perfusion indices signal potential microvascular dysfunction preceding atherosclerosis and other cardiometabolic pathologies. Post-occlusive reactive hyperemia (PORH), a vasodilatory response following a mechanically induced ischemia, is a transient increase in perfusion and can assess microvascular function. The greatest blood flow change corresponding to the first minute of hyperemia (represented by time-to-peak, hyperemic velocity, AUC within 1st min) has been shown to indicate microvascular dysfunction. However, the reproducibility of these temporal kinetic indices of the PORH response is unknown. Our aim was to examine the inter- and intra-day reproducibility and standardization of reactive hyperemia, with emphasis on the kinetic indices of PORH, using laser speckle contrast imaging (LSCI) technique., Methods and Results: Seventeen healthy adults (age = 24 ± 3 years) completed three PORH bouts over two lab visits. LSCI region of interest was a standardized 10 cm region on the dominant ventral forearm. A 5-min brachial artery occlusion period induced by inflating an arm cuff to 200 mmHg, preceded a 4-min hyperemic period. Inter- and intra-day reliability and reproducibility of cutaneous vascular conductance (LSCI flux / mean arterial pressure) were determined using intraclass correlation (ICC) and coefficient of variation (CV%). Maximal flow and area under the curve standardized to zero perfusion showed intra- and inter-day reliability (ICC > 0.70). Time to maximal flow (TMF) was not reproducible (inter-day CV = 18%). However, alternative kinetic indices such as 1-min AUC and overshoot rate-of-change (ORC), represented as a piecewise function (at 5s, 10s, 15s, and 20s into hyperemia), were reproducible (CV< 11%). Biological zero was a reliable normalization point., Conclusion: PORH measured with LSCI is a reliable assessment of microvascular function. However, TMF or its derived hyperemic velocity are not recommended for longitudinal assessment. Piecewise ORC and 1-min AUC are reliable alternatives to assess the kinetic response of PORH., Competing Interests: The authors have declared that no competing interests exist.

Nonmotor symptoms are common in Parkinson's disease (PD) and they include dysregulation of cardiovascular system, which adversely affects quality of life. Recent studies provide indirect evidence that baroreflex dysfunction may be one of the mechanisms of cardiovascular dysregulation in PD. Herein, we tested the hypothesis that the baroreflex gain, assessed across an extensive range of the reflex arc by eliciting rapid changes in blood pressure (BP) induced by sequential boluses of vasoactive drugs (modified-Oxford technique) would be attenuated in middle-aged patients with PD. Beat-to-beat heart rate (electrocardiography) and BP (finger photoplethysmography) were obtained during 10 min of supine rest preceding the modified-Oxford (bolus of nitroprusside followed by phenylephrine 1 min afterward) in 11 patients with PD (51 ± 6 yr) and 7 age-matched controls (47 ± 6 yr). The resulting systolic BP and R-R interval responses were plotted and fitted with segmental linear regression and symmetric sigmoid model. Spontaneous indices obtained via sequence technique were also used to estimate baroreflex gain. Compared with controls, the estimated gains measured by segmental linear regression (patients: 3.83 ± 2.6 ms/mmHg versus controls: 7.78 ± 1.7 ms/mmHg; P = 0.003) and symmetric sigmoid model (patients: 12.36 ± 6.9 ms/mmHg versus controls: 32.02 ± 19.0 ms/mmHg; P = 0.009) were lower in patients with PD. The operating range of BP was larger in patients with PD compared with controls (13 ± 7 mmHg versus controls: 7 ± 3 mmHg; P = 0.032). Of note, the gain obtained from spontaneous indices was similar between groups. These data indicate that baroreflex gain was reduced by >50% in PD, thereby providing clear and direct evidence that cardiovagal baroreflex dysfunction occurs in PD. NEW & NOTEWORTHY Attenuated baroreflex gain may contribute to adverse cardiovascular outcomes, including orthostatic intolerance symptoms typically observed in patients with Parkinson's disease. We found that the baroreflex gain (assessed by the modified-Oxford technique) is attenuated and accompanied by an increased operating range in patients with Parkinson's disease. These findings highlight that cardiovascular perturbations are required to detect baroreflex impairments and that spontaneous indices do not reveal cardiovagal-baroreflex dysfunction in a middle-aged group of patients with Parkinson's disease.

New Findings: What is the central question of this study? Delayed cardiovascular responses occur following a single bout of remote ischaemic preconditioning (RIPC). Is heart rate variability (HRV), a surrogate marker of cardiac vagal control, able to detect a delayed effect after a single bout of RIPC? Do repeated bouts of RIPC further alter HRV? What is the main finding and its importance? Indices of HRV indicated a shift in sympathovagal balance toward greater parasympathetic activity following 2 weeks of RIPC but not after a single bout of RIPC. Thus, repeated bouts of RIPC were necessary to elicit changes in autonomic function., Abstract: Remote ischaemic preconditioning (RIPC), induced by brief periods of ischaemia followed by reperfusion, protects against ischaemia-reperfusion injury and improves microvascular function. However, the effect of RIPC on autonomic function remains unclear. We hypothesized that RIPC, administered as a single bout or repeated over a 2-week period, will increase markers of cardiac vagal control measured by heart rate variability (HRV). Thirty-two young adults performed a single bout (n = 13), repeated bouts (n = 11), or served as a time control (n = 8). RIPC sessions consisted of four repetitions of 5 min unilateral brachial artery occlusion interspersed by 5 min of reperfusion. For the single bout protocol, resting lead II electrocardiogram (ECG) was collected before and 24, 48, 72 and 168 h post-RIPC. The repeated bout protocol consisted of three 4-day periods of RIPC training, each interspersed by a 1-day break. Similar to time controls, ECG was collected before and 24 h after the last RIPC bout. HRV was analysed by power spectral density and symbolic dynamics using 350-beat ECG segments. After a single bout of RIPC, no changes in HRV were observed at any time point (P > 0.05). After 2 weeks of repeated RIPC, the percentage of zero-variation fragments (baseline = 13.1 ± 1.9%, post-RIPC = 6.9 ± 1.5%, P < 0.05) and the LF/HF ratio decreased (baseline = 1.1 ± 0.2, post-RIPC = 0.7 ± 0.1, P < 0.01), whereas the percentage of two-variation fragments increased (baseline = 42.9 ± 3.6%, post-RIPC = 52.5 ± 3.0%, P < 0.01). These data indicate that repeated RIPC is necessary to elicit changes in sympathovagal balance, specifically resulting in increased vagal and decreased sympathetic activity., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

Purpose: To evaluate the independent and combined associations of cardiorespiratory fitness (CRF) and muscular strength (MS) with arterial stiffness (AS), a strong predictor of cardiovascular disease, in older adults., Methods: This cross-sectional study included 405 older adults (mean age, 72 yr). Cardiorespiratory fitness was assessed by time (s) to complete a 400-m walking test and MS by maximal handgrip strength (kg). Carotid-femoral pulse wave velocity was used to assess AS. High AS was defined as a pulse wave velocity of ≥10 m·s, a previously established threshold for increased cardiovascular risk. Poisson regression was used to calculate prevalence ratios (PR) and 95% confidence intervals (CI) of having high AS across sex-specific tertiles of CRF and MS. Muscular strength and CRF were further dichotomized into either "weak" or "unfit" (lower one third for each), or "strong" or "fit" (upper two thirds for each) to investigate the combined associations of CRF and MS with high AS. All analyses were adjusted for potential confounders, including MS for CRF and CRF for MS., Results: Sixty-nine (17%) participants had high AS. Compared with lower CRF, PR (95% CI) of having high AS were 0.53 (0.30-0.95) and 0.69 (0.38-1.23) for middle and upper CRF, respectively. Compared with lower MS, PR (95% CI) of having high AS were 0.81 (0.49-1.34) and 0.52 (0.29-0.92) for middle and upper MS, respectively. In the joint analysis, compared with the "unfit and weak" group, PR (95% CI) of having high AS were 0.72 (0.38-1.35), 0.58 (0.29-1.16), and 0.46 (0.25-0.85) for "unfit and strong," "fit and weak," and "fit and strong" groups, respectively., Conclusions: Higher levels of CRF and MS were independently associated with lower (healthier) levels of AS in older adults.

Opioids play a critical role in acute postoperative pain management. Our objective was to develop machine learning models to predict postoperative opioid requirements in patients undergoing ambulatory surgery. To develop the models, we used a perioperative dataset of 13,700 patients (≥ 18 years) undergoing ambulatory surgery between the years 2016-2018. The data, comprising of patient, procedure and provider factors that could influence postoperative pain and opioid requirements, was randomly split into training (80%) and validation (20%) datasets. Machine learning models of different classes were developed to predict categorized levels of postoperative opioid requirements using the training dataset and then evaluated on the validation dataset. Prediction accuracy was used to differentiate model performances. The five types of models that were developed returned the following accuracies at two different stages of surgery: 1) Prior to surgery-Multinomial Logistic Regression: 71%, Naïve Bayes: 67%, Neural Network: 30%, Random Forest: 72%, Extreme Gradient Boost: 71% and 2) End of surgery-Multinomial Logistic Regression: 71%, Naïve Bayes: 63%, Neural Network: 32%, Random Forest: 72%, Extreme Gradient Boost: 70%. Analyzing the sensitivities of the best performing Random Forest model showed that the lower opioid requirements are predicted with better accuracy (89%) as compared with higher opioid requirements (43%). Feature importance (% relative importance) of model predictions showed that the type of procedure (15.4%), medical history (12.9%) and procedure duration (12.0%) were the top three features contributing to model predictions. Overall, the contribution of patient and procedure features towards model predictions were 65% and 35% respectively. Machine learning models could be used to predict postoperative opioid requirements in ambulatory surgery patients and could potentially assist in better management of their postoperative acute pain., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: BGN owns equity in Perimatics LLC and serves as its advisor. The University of Washington provided support in the form of salaries for some of the authors [BGN, JDL, CTF]. Perimatics LLC provided support in the form of salaries for some of the authors [NV, RV, LB]. VA Puget Sound Health System provided support in the form of salaries for the author [MH]. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Chest imaging often incidentally finds indeterminate nodules that need to be monitored to ensure early detection of lung cancers. Health care systems need effective approaches for identifying these lung nodules. We compared the diagnostic performance of 2 approaches for identifying patients with lung nodules on imaging studies (chest/abdomen): (1) relying on radiologists to code imaging studies with lung nodules; and (2) applying a text search algorithm to identify references to lung nodules in radiology reports., Methods: We assessed all radiology studies performed between January 1, 2016 and November 30, 2016 in a single Veterans Health Administration hospital. We first identified imaging reports with a diagnostic code for a pulmonary nodule. We then applied a text search algorithm to identify imaging reports with key words associated with lung nodules. We reviewed medical records for all patients with a suspicious radiology report based on either search strategy to confirm the presence of a lung nodule. We calculated the yield and the positive predictive value (PPV) of each search strategy for finding pulmonary nodules., Results: We identified 12,983 imaging studies with a potential lung nodule. Chart review confirmed 8,516 imaging studies with lung nodules, representing 2,912 unique patients. The text search algorithm identified all the patients with lung nodules identified by the radiology coding (n = 1,251) as well as an additional 1,661 patients. The PPV of the text search was 72% (2,912/4,071) and the PPV of the radiology code was 92% (1,251/1,363). Among the patients with nodules missed by radiology coding but identified by the text search algorithm, 130 had lung nodules > 8 mm in diameter., Conclusions: The text search algorithm can identify additional patients with lung nodules compared to the radiology coding; however, this strategy requires substantial clinical review time to confirm nodules. Health care systems adopting nodule-tracking approaches should recognize that relying only on radiology coding might miss clinically important nodules., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to the article., (Copyright © 2020 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Introduction: During cold exposure, an increase in sympathetic nerve activity evokes vasoconstriction (VC) of cutaneous vessels to minimize heat loss. In older adults, this reflex VC response is impaired thereby increasing their susceptibility to excess heat loss and hypothermia. Because L-tyrosine, the amino acid substrate necessary for catecholamine production, has been shown to augment reflex VC in age skin, we hypothesize that oral ingestion of L-tyrosine will attenuate the decline in core temperature (Tc) during whole-body cooling in older adults., Methods: In a randomized, double-blind design, nine young (25 ± 3 yr) and nine older (72 ± 8 yr) participants ingested either 150 mg·kg of L-tyrosine or placebo before commencing 90 min of whole-body cooling to decrease skin temperature to approximately 29.5°C. Esophageal temperature and forearm laser Doppler flux (LDF) were measured continuously throughout the protocol to provide an index of Tc and skin blood flow, respectively. The change in esophageal temperature (ΔTES) was the difference in temperature at the end of cooling subtracted from baseline. Cutaneous vascular conductance (CVC) was calculated as CVC = LDF/mean arterial pressure and expressed as a percent change from baseline (%ΔCVCBASELINE)., Results: Oral tyrosine ingestion augmented the cutaneous VC response to cooling in older adults (placebo, 14.4 ± 2.0; tyrosine, 32.7% ± 1.7% ΔCVCBASELINE; P < 0.05). Additionally, tyrosine improved Tc maintenance throughout cooling in older adults (placebo, -0.29 ± 0.07; tyrosine, -0.07 ± 0.07 ΔTES; P < 0.05). Both the cutaneous VC and Tc during cooling were similar between young and older adults supplemented with tyrosine (P > 0.05)., Conclusions: These results indicate that L-tyrosine supplementation improves Tc maintenance in response to acute cold exposure in an older population.

One week of daily remote ischemic preconditioning (RIPC) improves cutaneous vasodilatory (VD) function. However, the underlying mechanisms and the number of sessions needed to optimize this adaptive response remain unclear. We hypothesized that the responses to localized heating of the skin will be greater after 2 wk as opposed to 1 wk of RIPC. Furthermore, 2 wk of repeated RIPC will augment cutaneous VD responses to thermal and pharmacological stimuli. In methods, twenty-four participants (24 ± 2 yr; 13 men, 11 women) performed repeated RIPC (7 daily sessions over 1 wk, n = 11; 12 sessions over 2 wk, n = 13), consisting of four repetitions of 5 min of arm blood flow occlusion separated by 5 min reperfusion. Laser speckle contrast imaging was used to measure skin blood flow responses, in perfusion units (PU), to local heating (T loc  = 42°C), acetylcholine (ACh), and sodium nitroprusside (SNP) before and after repeated RIPC. Data were expressed as cutaneous vascular conductance (CVC, in PU/mmHg). In results, the VD response to local heating increased after RIPC (∆CVC from baseline; 1 wk: 0.94 ± 0.11 to 1.19 ± 0.15, 2 wk: 1.18 ± 0.07 to 1.33 ± 0.10 PU/mmHg; P < 0.05) but the ∆CVC did not differ between weeks. SNP-induced VD increased after 2 wk of RIPC (∆CVC; 0.34 ± 0.07 to 0.63 ± 0.11 PU/mmHg; P < 0.05), but ACh-induced VD did not. In conclusion, repeated RIPC improves local heating- and SNP-mediated cutaneous VD. When compared with 1 wk of RIPC, 2 wk of RIPC does not induce further improvements in cutaneous VD function. NEW & NOTEWORTHY Repeated RIPC increases the cutaneous vasodilatory response to local heating and to sodium nitroprusside but not to acetylcholine. Thus, endothelial-independent and local heating-mediated cutaneous vasodilation are improved following RIPC. However, 2 wk of RIPC sessions are not more effective than 1 wk of RIPC sessions in enhancing local heating-mediated cutaneous vasodilation.

Angiotensin II (ANG II) is locally produced in human skin and contributes to the reflex vasoconstriction (VC) response in aged but not young skin. We hypothesized that the exogenous ANG II-mediated VC response would be greater in older adults and would be affected by inhibition of adrenoreceptor or ANG II type II receptor (AT 2 R) pathways. Three microdialysis (MD) fibers were placed in the forearm skin of 11 young (26 ± 3 yr) and 11 older (68 ± 4 yr) individuals for perfusion of 1) Ringer solution (control), 2) adrenoreceptor blockade with yohimbine + propranolol, and 3) AT 2 R inhibition with PD-123319. ANG II was then added to the perfusates at eight graded dose concentrations ranging from 10 -10 to 10 -3 M. Laser Doppler flux was measured at each MD site, and cutaneous vascular conductance (CVC) was calculated as CVC =  laser Doppler flux/mean arterial pressure and normalized to baseline CVC values collected before ANG II perfusion (%ΔCVC baseline ). At the control site, older adults (-34 ± 4%ΔCVC baseline ) exhibited a greater peak VC compared with young adults (-22 ± 2%ΔCVC baseline , P < 0.05), which was attenuated with adrenoreceptor blockade. Young skin exhibited a vasodilation in response to lower ANG II doses that was inhibited with AT 2 R inhibition. AT 2 R inhibition also increased the VC response to higher ANG II doses such that young skin responded similarly to older skin. These results indicate that ANG II has a greater VC influence in older than young individuals. Furthermore, ANG II may be affecting multiple targets, including adrenergic and AT 2 R pathways. NEW & NOTEWORTHY Intradermal perfusion of successive doses of angiotensin II (ANG II) revealed a role for ANG II type II receptors and dose-dependent, ANG II-mediated vasodilation in young but not older adults. In contrast, older adults exhibited greater vasoconstriction for a given dose of ANG II. The increased vasoconstriction in older adults was subsequently blunted with adrenoreceptor blockade, which indicates an interaction between ANG II and adrenergic signaling pathways in the cutaneous microcirculation.

Key Points: Remote ischaemic preconditioning (RIPC), induced by brief bouts of ischaemia followed by reperfusion, confers vascular adaptations that protect against subsequent bouts of ischaemia; however, the effect of RIPC repeated over several days on the human microcirculation is unknown. Using skin as a model, microvascular function was assessed at a control and a NO-inhibited area of skin before 1 day after and 1 week after administering seven consecutive days of repeated RIPC on the contralateral arm. Maximal vasodilatation was increased by ∼20-50% following 7 days of repeated RIPC, and this response remained elevated 1 week after stopping RIPC; however, NO-mediated vasodilatation was not affected by the RIPC stimulus. These data indicate that repeated RIPC augments maximal vasodilatation, but the underlying mechanism for this improvement is largely independent of NO. This finding suggests a role for other endothelium-derived mediators and/or for endothelium-independent adaptations with repeated RIPC., Abstract: Remote ischaemic preconditioning (RIPC), induced by intermittent periods of ischaemia followed by reperfusion, confers cardiovascular protection from subsequent ischaemic bouts. RIPC increases conduit and resistance vessel function; however, the effect of RIPC on the microvasculature remains unclear. Using human skin as a microvascular model, we hypothesized that cutaneous vasodilatory (VD) function elicited by localized heating would be increased following repeated RIPC. Ten participants (23 ± 1 years, 6 males, 4 females) performed RIPC for seven consecutive days. Each daily RIPC session consisted of 4 repetitions of 5 min of arm blood flow occlusion interspersed by 5 min reperfusion. Before, 1 day after and 1 week after the 7 days of RIPC, two microdialysis fibres were placed in ventral forearm skin for continuous infusion of Ringer solution or 20 mM l-NAME. Red blood cell flux was measured by laser Doppler flowmetry at each fibre site during local heating (T loc  = 39°C) and during maximal VD elicited by heating (T loc  = 43°C) and 28 mM sodium nitroprusside infusion. Data were normalized to cutaneous vascular conductance (flux/mmHg). Seven days of RIPC did not alter the nitric oxide (NO) contribution to the VD response to local heating (P > 0.05). However, the maximal VD was augmented (Pre: 2.5 ± 0.2, Post: 3.8 ± 0.5 flux/mmHg; P < 0.05) and remained elevated 1 week post RIPC (3.3 ± 0.4 flux/mmHg; P < 0.05). Repeated RIPC improves maximal VD but does not affect NO-mediated VD in the cutaneous microvasculature. This finding suggests that other factors may explain the vasodilatory adaptations that occur following repeated RIPC., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

Background: In young adults, blood flow restricted exercise (BFRE) at relatively low intensities can increase muscle strength as effectively as conventional high intensity training. Ischemic exercise can also increase collateral blood flow in skeletal muscle. However, the effects of chronic BFRE on muscle strength and blood flow in older adults remain unknown. The purpose of this study was to compare the effects of 4weeks of BFRE training on skeletal muscle strength and blood flow between young and older subjects and between older adults performing BFRE and conventional high intensity resistance exercise., Methods: Maximum voluntary contraction (MVC), forearm girth, peak forearm blood flow (FBF) and forearm vascular conductance (FVC) were assessed before and after 4weeks of forearm resistance training with BFRE in older adults (O-BFRE, 63±1 y, n=9) and younger adults (Y-BFRE, 22±1 y, n=8) and with high intensity training at 75% maximum voluntary contraction in older adults (O-HI, 63±1 y, n=10)., Results: MVC increased in all groups (O-BFRE, 33.4±4.7 to 36.3±4.7kg; Y-BFRE, 37.2±4.9 to 43.0±5.0kg; O-HI, 34.0±4.4 to 39.8±4.4kg; all p<0.05). Forearm girth increased in O-BFRE (26.3±1.1 to 26.7±1.1cm; p<0.05) and Y-BFRE (23.9±0.9 to 25.1±1.5cm; p<0.05) but not in O-HI (25.9±1.0 to 26.1±1.0cm; p=0.26). Peak forearm vascular conductance increased in Y-BFRE (0.190±0.016 to 0.311±0.031units; p=0.01) but not in O-BFRE (0.157±0.024 to 0.193±0.029units; p=0.48) and O-HI (0.188±0.035 to 0.227±0.035units; p=0.18)., Conclusion: These data suggest that chronic BFRE training is effective in increasing muscular strength, muscle size and vascularity in young adults but, in older adults, increases only muscular strength and size. Longer training durations or higher volumes may be required to evoke similar vascular adaptations in older adults., (Copyright © 2017 Elsevier Inc. All rights reserved.)

New Findings: What is the central question of this study? Ageing is associated with altered sympathetic responses to stress, which are explained in part by reduced noradrenergic function. The impact of supplementation with oral l-tyrosine, the amino acid precursor for catecholamine synthesis, on the effector responses to cold and exercise stress has yet to be examined. What is the main finding and its importance? Oral l-tyrosine ingestion augmented the sympathetically mediated vasoconstriction response to cold exposure in aged skin. This suggests that l-tyrosine supplementation might improve thermoregulatory function in older adults. l-Tyrosine is the primary substrate for noradrenaline biosynthesis within sympathetic axon terminals. In stressful conditions requiring increased catecholamine production, the axonal l-tyrosine concentration may limit the full expression of the sympathetic effector response and this may be particularly evident in older adults. We hypothesize that oral l-tyrosine supplementation will increase the sympathetic response to whole-body cooling and muscle metaboreflex activation. In a randomized, double-blind design, 11 young (Y = 24 ± 1 years) and 11 older participants (O = 68 ± 4 years) ingested either 150 mg kg -1 of l-tyrosine or placebo before commencing 30 min of whole-body cooling to induce a gradual decline in skin temperature from 34 to 30.5°C. Laser Doppler flux (LDF) was measured at the ventral forearm, and cutaneous vascular conductance (CVC) was calculated as CVC = LDF/mean arterial pressure and expressed as a percentage change from baseline (%ΔCVC). Two minutes of static hand-grip exercise (35% maximal voluntary contraction) followed by 3 min of postexercise ischaemia were implemented before and toward the end of the cooling bout. l-Tyrosine supplementation did not affect blood pressure or heart rate responses to exercise or postexercise ischaemia. However, the blunted vasoconstriction response to whole-body cooling in older adults (placebo: Y = 39 ± 5%ΔCVC and O = 16 ± 2 %ΔCVC; P < 0.05) was augmented after l-tyrosine supplementation (l-tyrosine: Y = 40 ± 4%ΔCVC and O = 32 ± 5 %ΔCVC; P < 0.05). These results suggest that l-tyrosine bioavailability might limit thermoregulatory function in an older population., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

New Findings: What is the central question of this study? In young adults, about half of the cold-related reduction in skin blood flow during cold exposure is mediated by noradrenaline, while the remainder is attributable to other substances co-released with noradrenaline that have yet to be identified. What is the main finding and its importance? Purinergic receptor blockade blunted the vasoconstriction response to whole-body cooling and to intradermal administration of tyramine. These results indicate that ATP is necessary to vasoconstrict blood vessels in the skin adequately and prevent heat loss in a cold environment. Noradrenaline is responsible for eliciting ∼60% of the reflex cutaneous vasoconstriction (VC) response in young adults, while the remainder is attributable to one or more unidentified co-released sympathetic adrenergic neurotransmitter(s). Inconsistent evidence has placed neuropeptide Y in this role; however, other putative cotransmitters have yet to be tested. We hypothesize that ATP contributes to the reflex cutaneous VC response. Two protocols were conducted in young adults (n = 10); both involved the placement of three microdialysis probes in forearm skin and whole-body cooling (skin temperature = 30.5°C). In protocol 1, the following solutions were infused: (i) lactated Ringer solution (control); (ii) 10 mm l-NAME; and (iii) purinergic receptor blockade with 1 mm suramin plus l-NAME. In protocol 2, the following solutions were infused: (i) lactated Ringer solution; (ii) suramin plus l-NAME; and (iii) suramin plus l-NAME plus adrenoreceptor blockade with 5 mm yohimbine plus 1 mm propranolol. Laser Doppler flux (LDF) was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP) and expressed as percentage changes from baseline (%ΔCVC BASELINE ). l-NAME was used to block the vasodilatory influence of ATP and unmask the P 2 X-mediated VC response to exogenous ATP infusion (-21 ± 6%ΔCVC BASELINE ). During cooling, the VC response (control, -39 ± 8%ΔCVC BASELINE ) was attenuated at the suramin site (-21 ± 4%ΔCVC BASELINE ) and further blunted with combined adrenoreceptor blockade (-9 ± 3%ΔCVC BASELINE ; P < 0.05). Compared with the control site (-22 ± 5%ΔCVC BASELINE ), suramin inhibited pharmacologically induced VC to tyramine (-12 ± 6%ΔCVC BASELINE ; P < 0.05), which displaces adrenergic neurotransmitters from axon terminals. These data indicate that ATP contributes to the cutaneous VC response in humans., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

Key Points: Lung aeration at birth significantly increases pulmonary blood flow, which is unrelated to increased oxygenation or other spatial relationships that match ventilation to perfusion. Using simultaneous X-ray imaging and angiography in near-term rabbits, we investigated the relative contributions of the vagus nerve and oxygenation to the increase in pulmonary blood flow at birth. Vagal denervation inhibited the global increase in pulmonary blood flow induced by partial lung aeration, although high inspired oxygen concentrations can partially mitigate this effect. The results of the present study indicate that a vagal reflex may mediate a rapid global increase in pulmonary blood flow in response to partial lung aeration., Abstract: Air entry into the lungs at birth triggers major cardiovascular changes, including a large increase in pulmonary blood flow (PBF) that is not spatially related to regional lung aeration. To investigate the possible underlying role of a vagally-mediated stimulus, we used simultaneous phase-contrast X-ray imaging and angiography in near-term (30 days of gestation) vagotomized (n = 15) or sham-operated (n = 15) rabbit kittens. Rabbits were imaged before ventilation, when one lung was ventilated (unilateral) with 100% nitrogen (N 2 ), air or 100% oxygen (O 2 ), and after all kittens were switched to unilateral ventilation in air and then ventilation of both lungs using air. Compared to control kittens, vagotomized kittens had little or no increase in PBF in both lungs following unilateral ventilation when ventilation occurred with 100% N 2 or with air. However, relative PBF did increase in vagotomized animals ventilated with 100% O 2 , indicating the independent stimulatory effects of local oxygen concentration and autonomic innervation on the changes in PBF at birth. These findings demonstrate that vagal denervation inhibits the previously observed increase in PBF with partial lung aeration, although high inspired oxygen concentrations can partially mitigate this effect., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

Lung aeration stimulates the increase in pulmonary blood flow (PBF) at birth, but the spatial relationships between PBF and lung aeration and the role of increased oxygenation remain unclear. Using simultaneous phase-contrast X-ray imaging and angiography, we have investigated the separate roles of lung aeration and increased oxygenation in PBF changes at birth using near-term (30 days of gestation) rabbit kits (n = 18). Rabbits were imaged before ventilation, then the right lung was ventilated with 100% nitrogen (N2), air or 100% O2 (oxygen), before all kits were switched to ventilation in air, followed by ventilation of both lungs using air. Unilateral ventilation of the right lung with 100% N2 significantly increased heart rate (from 69.4 ± 4.9 to 93.0 ± 15.0 bpm), the diameters of both left and right pulmonary axial arteries, number of visible vessels in both left and right lungs, relative PBF index in both pulmonary arteries, and reduced bolus transit time for both left and right axial arteries (from 1.34 ± 0.39 and 1.81 ± 0.43 s to 0.52 ± 0.17 and 0.89 ± 0.21 s in the left and right axial arteries, respectively). Similar changes were observed with 100% oxygen, but increases in visible vessel number and vessel diameter of the axial arteries were greater in the ventilated right lung during unilateral ventilation. These findings confirm that PBF increase at birth is not spatially related to lung aeration and that the increase in PBF to unventilated regions is unrelated to oxygenation, although oxygen can potentiate this increase., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Stimulation of angiotensin II type I receptors (AT1R) elicits vasoconstriction (VC) that may be occurring through the activation of a pathogenic vascular pathway such as Rho kinase (ROCK). We hypothesize that reflex cutaneous VC to whole body cooling (mean skin temperature = 30.5°C) in older humans relies in part on AT1R activation, which may explain greater ROCK activity attendant with aging. Two microdialysis (MD) fibers were placed in the forearm skin of 10 young (Y; 24 ± 1 yr) and 10 older (O; 70 ± 2 yr) individuals for infusion of 1) lactated Ringer's solution (switched to fasudil, a ROCK antagonist, after cooling); and 2) AT1R blockade with losartan. Laser Doppler flux (LDF) was measured over each MD site and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/mean arterial pressure) and expressed as percent change from baseline (%ΔCVCBASELINE). In older individuals the VC response to whole body cooling was blunted (Y = -34 ± 2, O = -17 ± 3%ΔCVC) and was further attenuated at the losartan site (Y = -34 ± 3, O = -9 ± 3%ΔCVC; P < 0.05). The VC response to an exogenous 10-μM dose of angiotensin II (Y = -27 ± 3, O = -42 ± 5%ΔCVC) was completely blocked in sites pretreated with losartan or with fasudil. These data suggest that AT1R activation contributes to the reflex VC response in aged but not young skin. Furthermore, the angiotensin II component of the VC response appears to occur primarily through a ROCK-mediated mechanism., (Copyright © 2015 the American Physiological Society.)

At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large increase in pulmonary blood flow (PBF). Current theories predict that the increase in PBF is spatially related to ventilated lung regions as they aerate after birth. Using simultaneous phase-contrast X-ray imaging and angiography we investigated the spatial relationships between lung aeration and the increase in PBF after birth. Six near-term (30-day gestation) rabbits were delivered by caesarean section, intubated and an intravenous catheter inserted, before they were positioned for X-ray imaging. During imaging, iodine was injected before ventilation onset, after ventilation of the right lung only, and after ventilation of both lungs. Unilateral ventilation increased iodine levels entering both left and right pulmonary arteries (PAs) and significantly increased heart rate, iodine ejection per beat, diameters of both left and right PAs, and number of visible vessels in both lungs. Within the 6th intercostal space, the mean gray level (relative measure of iodine level) increased from 68.3 ± 11.6 and 70.3 ± 7.5%·s to 136.3 ± 22.6 and 136.3 ± 23.7%·s in the left and right PAs, respectively. No differences were observed between vessels in the left and right lungs, despite the left lung not initially being ventilated. The increase in PBF at birth is not spatially related to lung aeration allowing a large ventilation/perfusion mismatch, or pulmonary shunting, to occur in the partially aerated lung at birth., (Copyright © 2014 the American Physiological Society.)

Background: Studies across a range of specialties have consistently yielded positive associations between performance on in-training examinations and board certification examinations, supporting the use of the in-training examination as a valuable formative feedback tool for residents and residency programs. That association to date, however, has not been tested in child and adolescent psychiatry residents., Objective: This is the first study to explore the relationship between performance on the American College of Psychiatrists' Child Psychiatry Resident In-Training Examination (CHILD PRITE) and subsequent performance on the American Board of Psychiatry and Neurology's (ABPN) subspecialty multiple-choice examination (Part I) in child and adolescent psychiatry (CAP)., Methods: Pearson correlation coefficients were used to examine the relationship between performance on the CHILD PRITE and the CAP Part I examination for 342 fellows., Results: Second-year CAP fellows performed significantly better on the CHILD PRITE than did the first-year fellows. The correlation between the CHILD PRITE total score and the CAP Part I examination total score was .41 (P  =  .01) for first-year CAP fellows; it was .52 (P  =  .01) for second-year CAP fellows., Conclusions: The significant correlations between scores on the 2 tests show they assess the same achievement domain. This supports the use of the CHILD PRITE as a valid measure of medical knowledge and formative feedback tool in child and adolescent psychiatry.

Acute leg exercise increases brachial artery retrograde shear rate (SR), while chronic exercise improves vasomotor function. These combined observations are perplexing given the proatherogenic impacts of retrograde shear stress on the vascular endothelium and may be the result of brief protocols used to study acute exercise responses. Therefore, we hypothesized that brachial artery retrograde SR increases initially but subsequently decreases in magnitude during prolonged leg cycling. Additionally, we tested the role of cutaneous vasodilation in the elimination of increased retrograde SR during prolonged exercise. Brachial artery diameter and velocity profiles and forearm skin blood flow and temperature were measured at rest and during 50 min of steady-state, semirecumbent leg cycling (120 W) in 14 males. Exercise decreased forearm vascular conductance (FVC) and increased retrograde SR at 5 min (both P < 0.05), but subsequently forearm and cutaneous vascular conductance (CVC) rose while retrograde SR returned toward baseline values. The elimination of increased retrograde SR was related to the increase in FVC (r(2) = 0.58; P < 0.05) and CVC (r(2) = 0.32; P < 0.05). Moreover, when the forearm was cooled via a water-perfused suit between minutes 30 and 40 to blunt cutaneous vasodilation attending exercise, FVC was reduced and the magnitude of retrograde SR was increased from -49.7 ± 13.6 to -78.4 ± 16.5 s(-1) (P < 0.05). Importantly, these responses resolved with removal of cooling during the final 10 min of exercise (retrograde SR: -46.9 ± 12.5 s(-1)). We conclude that increased brachial artery retrograde SR at the onset of leg cycling subsequently returns toward baseline values due in part to thermoregulatory cutaneous vasodilation during prolonged exercise.