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The diversity of retinal imaging devices poses a significant challenge: domain shift, which leads to performance degradation when applying the deep learning models trained on one domain to new testing domains. In this paper, we propose a multi-scale input along with multiple domain adaptors applied hierarchically in both feature and output spaces. The proposed training strategy and novel unsupervised domain adaptation framework, called Collaborative Adversarial Domain Adaptation (CADA), can effectively overcome the challenge. Multi-scale inputs can reduce the information loss due to the pooling layers used in the network for feature extraction, while our proposed CADA is an interactive paradigm that presents an exquisite collaborative adaptation through both adversarial learning and ensembling weights at different network layers. In particular, to produce a better prediction for the unlabeled target domain data, we simultaneously achieve domain invariance and model generalizability via adversarial learning at multi-scale outputs from different levels of network layers and maintaining an exponential moving average (EMA) of the historical weights during training. Without annotating any sample from the target domain, multiple adversarial losses in encoder and decoder layers guide the extraction of domain-invariant features to confuse the domain classifier. Meanwhile, the ensembling of weights via EMA reduces the uncertainty of adapting multiple discriminator learning. Comprehensive experimental results demonstrate that our CADA model incorporating multi-scale input training can overcome performance degradation and outperform state-of-the-art domain adaptation methods in segmenting retinal optic disc and cup from fundus images stemming from the REFUGE, Drishti-GS, and Rim-One-r3 datasets., Comment: arXiv admin note: text overlap with arXiv:1910.07638

PURPOSE Neoadjuvant chemotherapy (NAC) is used to treat locally advanced breast cancer (LABC) and high-risk early breast cancer (BC). Pathological complete response (pCR) has prognostic value depending on BC subtype. Rates of pCR, however, can be variable. Predictive modeling is desirable to help identify patients early who may have suboptimal NAC response. Here, we test and compare the predictive performances of machine learning (ML) prediction models to a standard statistical model, using clinical and pathological data. METHODS Clinical and pathological variables were collected in 431 patients, including tumor size, patient demographics, histological characteristics, molecular status, and staging information. A standard multivariable logistic regression (MLR) was developed and compared with five ML models: k-nearest neighbor classifier, random forest (RF) classifier, naive Bayes algorithm, support vector machine, and multilayer perceptron model. Model performances were measured using a receiver operating characteristic (ROC) analysis and statistically compared. RESULTS MLR predictors of NAC response included: estrogen receptor (ER) status, human epidermal growth factor-2 (HER2) status, tumor size, and Nottingham grade. The strongest MLR predictors of pCR included HER2+ versus HER2− BC (odds ratio [OR], 0.13; 95% CI, 0.07 to 0.23; P < .001) and Nottingham grade G3 versus G1-2 (G1-2: OR, 0.36; 95% CI, 0.20 to 0.65; P < .001). The area under the curve (AUC) for the MLR was AUC = 0.64. Among the various ML models, an RF classifier performed best, with an AUC = 0.88, sensitivity of 70.7%, and specificity of 84.6%, and included the following variables: menopausal status, ER status, HER2 status, Nottingham grade, tumor size, nodal status, and presence of inflammatory BC. CONCLUSION Modeling performances varied between standard versus ML classification methods. RF ML classifiers demonstrated the best predictive performance among all models.

With the increase of cosmetic injectable hyaluronic acid (HA), there have been more cases with serious complications, including skin necrosis, blindness, and cerebral embolism. Patients who have recovered from HA filler-induced total vision loss are extremely rare. We report a case of a 27-year-old female who developed severe ocular pain on the right side and total vision loss following a 1.0 ml HA filler injection in the nasal dorsum. She arrived at our hospital 4 hours later. Her visual acuity was no light perception (NLP), and she exhibited eyelid ptosis, ophthalmoplegia, and frontal and nasal ecchymosis. She was promptly treated with subcutaneous and retrobulbar hyaluronidase injections, as well as intra-arterial 1500 IU hyaluronidase injections into the right ophthalmic artery with DSA assistance. Her vision improved from NLP to counting fingers at 1.0 meters. Unfortunately, 13 hours later, she felt an intense headache, and her vision again decreased to NLP. We immediately performed an injection of 1500 IU hyaluronidase combined with 8 mg alteplase for intra-arterial thrombolysis (IAT) into the right ophthalmic artery. Her vision improved immediately afterward. After 3 months, her visual acuity had significantly recovered from NLP (admission vision status) to 20/50 (Snellen chart with glasses). Similarly, skin, conjunctival, eye movement, and ptosis symptoms completely recovered. This case demonstrates that reversal of complete blindness due to embolism of the ophthalmic and central retinal arteries could be accomplished through multidisciplinary therapies, especially IAT using fibrinolytic agents combined with hyaluronidase followed by an anticoagulant regimen. Level of evidence VThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Various risk score calculators used to predict 30-day mortality after treatment of ruptured abdominal aortic aneurysms (rAAAs) have produced mixed results regarding their usefulness and reproducibility. We prospectively validated the accuracy of our preoperative scoring system in a modern cohort of patients with rAAAs.A retrospective review of all patients wiith rAAAs who had presented to a single academic center from January 2002 to December 2018 was performed. The patients were divided into three cohorts according to when the institutional practice changes had occurred: the pre-endovascular aneurysm repair (EVAR) era (January 2002 to July 2007), the pre-Harbor View risk score era (August 2007 to October 2013), and the modern era (November 2013 to December 2018). The primary outcome measure was 30-day mortality. Our preoperative risk score assigns 1 point for each of the following: age76 years, pH 7.2, creatinine2 mg/dL, and any episode of hypotension (systolic blood pressure 70 mm Hg). The previously reported mortality from a retrospective analysis of the first two cohorts was 22% for 1 point, 69% for 2 points, 78% for 3 points, and 100% for 4 points. The goal of the present study was to prospectively validate the Harborview scoring system in the modern era.During the 17-year study period, 417 patients with rAAAs were treated at our institution. Of the 118 patients treated in the modern era, 45 (38.1%) had undergone open aneurysm repair (OAR), 61 (51.7%) had undergone EVAR, and 12 (10.2%) had received comfort measures only. Excluding the 12 patients without aneurysm repair, we found a statistically significant linear trend between the preoperative risk score and subsequent 30-day mortality for all patients combined (P .0001), for OAR patients alone (P = .0003), and for EVAR patients alone (P .0001). After adjustment for the Harborview risk score, the 30-day mortality was 41.3% vs 31.6% after OAR vs EVAR, respectively (P = .2). For all repairs, the 30-day mortality was 14.6% for a score of 0, 35.7% for a score of 1, 68.4% for a score of 2, and 100% for a score of 3 or 4.Our results, representing one of the largest modern series of rAAAs treated at a single institution, have confirmed the accuracy of a simple 4-point preoperative risk score in predicting 30-day mortality in the modern rAAA patient. Such tools should be used when discussing the treatment options with referring physicians, patients, and their family members to help guide transfer and treatment decision-making.

Background Delays in diagnosis and treatment from first noticeable breast cancer symptoms are associated with poor outcomes. Understanding the reasons and barriers for patients’ delay in seeking medical care is critical to mitigating the problem. Methods In‐person surveys were conducted among 462 women, aged 18–79, with incident breast cancer cases, recruited from two cancer hospitals in North Vietnam. Delay, defined as the time interval between symptom recognition to the diagnosis and initiation of treatment equal to or exceeding 3 months, was categorized as follows: no delay (, A case cohort study found that delay in diagnosis and treatment of breast cancer is common among Vietnamese women and is affected by financial and physical barriers, psychological barriers, and lack of proper knowledge. Proper policy needs to be developed accordingly to address this public health issue.

In remote areas, extending a power line to the primary electricity grid can be very expensive and power losses are high, making connections to the grid almost impossible. A well-designed microgrid that integrates renewable energy resources can help remote areas reduce investment costs and power losses while providing a reliable power source. Therefore, investigating the design of an independent and economically practical microgrid system for these areas is necessary and plays an important role. This paper introduces a design procedure to design an isolated microgrid using HOMER software (HOMERPro 3.14.5) for remote areas. In Vietnam, due to the obstruction of the mountainous terrain or the isolated island location, many remote areas or islands need electrification. A simple case study of a hybrid system with a 60 kW peak load demand on Con Dao island in Vietnam is used to illustrate the proposed design method. Specifically, a hybrid system that includes a PV system, batteries, and a diesel generator is designed. To provide the full information of the designed hybrid system designed, each solution is analyzed and evaluated in detail according to the sensitivity parameters.

In this letter, we present an experimental demonstration of a Si optical modulator based on Fano-like resonance, which is the first of its kind in the literature. The Fano-like resonance is obtained through weak coupling between two optical resonators in the prototype device and a PN junction is designed for carrier-depletion type electro-refractive modulation. 20 Gb/s data rate on-off keying (OOK) is obtained experimentally on the prototype device. Compared with a ring resonator modulator with a similar optical resonance linewidth, a Fano-like resonance based modulator can potentially have a higher extinction ratio (ER) because the Fano-like resonance has an asymmetric spectrum line shape and the line shape on one side can be sharper than the Lorentz resonance line shape of a ring resonator.

PURPOSE To compare clinical outcomes in a cohort of patients with advanced non–small-cell lung cancer (NSCLC) with targetable genomic alterations detected using plasma-based circulating tumor DNA (ctDNA) or tumor-based next-generation sequencing (NGS) assays treated with US Food and Drug Administration–approved therapies at a large academic research cancer center. METHODS A retrospective review from our MD Anderson GEMINI database identified 2,224 blood samples sent for ctDNA NGS testing from 1971 consecutive patients with a diagnosis of advanced NSCLC. Clinical, treatment, and outcome information were collected, reviewed, and analyzed. RESULTS Overall, 27% of the ctDNA tests identified at least one targetable mutation and 73% of targetable mutations were EGFR-sensitizing mutations. Among patients treated with first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapies, there were no significant differences in progression-free survival of 379 days and 352 days ( P value = .41) with treatment based on tissue (n = 40) or ctDNA (n = 40), respectively. Additionally, there were no differences in progression-free survival or objective response rate among those with low (n = 8, 0.01%-0.99%) versus high (n = 16, ≥ 1%) levels of ctDNA of the targetable mutation as measured by variant allele frequency (VAF). Overall, there was excellent testing concordance (n = 217 tests) of > 97%, sensitivity of 91.7%, and specificity of 99.7% between blood-based ctDNA NGS and tissue-based NGS assays. CONCLUSION There were no significant differences in clinical outcomes among patients treated with approved EGFR-TKIs whose mutations were identified using either tumor- or plasma-based comprehensive profiling and those with very low VAF as compared with high VAF, supporting the use of plasma-based profiling to guide initial TKI use in patients with metastatic EGFR-mutant NSCLC.

Objective:To examine temporal trends and geographic variations and predict inpatient rehabilitation (IPR) length of stay (LOS) and home discharge for stroke patients.Methods:Patients aged ≥18 years who were admitted to an IPR facility in Alberta, Canada, between 04/2014 and 03/2018 (years 2014–2017) were included. Predictors of LOS and home discharge were examined using 2014–2016 data and validated using 2017 data. Multivariable linear regression (MLR), multivariable negative binomial (MNB), and multivariable quantile regressions (MQR) were used to examine LOS, and logistic regression was used for home discharge.Results:We included 2686 rehabilitation admissions between 2014 and 2017. The mean LOS decreased (2014: 71 days; 2017: 62.1 days; p = 0.003) during the study period and was shortest in Edmonton (59.1 days) compared to Calgary (66 days) or other localities (70.8 days; p < 0.001). Three-quarters of patients were discharged home and this proportion remained unchanged between 2014 and 2017. Calgary patients were more likely to be discharged home than those in Edmonton (OR = 0.62; p = 0.019) or other localities (OR = 0.39; p = 0.011). The MLR and MNB models provided accurate prediction for the mean LOS (predicted = 59.9 and 60.8 days, respectively, vs. actual = 62.1 days; both p > 0.5), while the MQR model did so for the median LOS (predicted = 44.3 days vs. actual = 44 days; p = 0.09). The logistic regression resulted in 82.4% of correct prediction, a sensitivity of 91.6%, and a specificity of 50.7% for home discharge.Conclusions:Rehabilitation LOS decreased while the proportion of home discharge remained unchanged during the study period. Both varied across health zones. Identifiable statistical models provided accurate prediction with a separate patient cohort.

Recently, unmanned aerial vehicles (UAVs) enhance connectivity and accessibility for civilian and military applications. A group of UAVs with on-board cameras usually monitors or collects information about designated areas. The UAVs can build a distributed network to share/exchange and to process collected sensing data before sending to a data processing center. A huge data transmission among them may cause latency and high-energy consumption. This paper deploys artificial intelligent (AI) techniques to process the video data streaming among the UAVs. Thus, each distributed UAV only needs to send a certain required information to each other. Each UAV processes data utilizing AI and only sends the data that matters to the others. The UAVs, formed as a connected network, communicate within a short communication range and share their own data to each other. Convolution neural network (CNN) technique extracts feature from images automatically that the UAVs only send the moving objects instead of the whole frames. This significantly reduces redundant information for either each UAV or the whole network and saves a huge energy consumption for the network. The UAVs can also save energy for their motion in the sensing field. In addition, a flocking control algorithm is deployed to lead the group of UAVs in the working fields and to avoid obstacles if needed. Simulation and experimental results are provided to verify the proposed algorithms in either AI-based data processing or controlling the UAVs. The results show promising points to save energy for the networks.

Neurovascular coupling is a key control mechanism in cerebral blood flow (CBF) regulation. Importantly, this process was demonstrated to be affected in several neurological disorders, including epilepsy. Neurovascular coupling (NVC) is the basis for functional brain imaging, such as PET, SPECT, fMRI, and fNIRS, to assess and map neuronal activity, thus understanding NVC is critical to properly interpret functional imaging signals. However, hemodynamics, as assessed by these functional imaging techniques, continue to be used as a surrogate to map seizure activity; studies of NVC and cerebral blood flow control during and following seizures are rare. Recent studies have provided conflicting results, with some studies showing focal increases in CBF at the onset of a seizure while others show decreases. In this brief review article, we provide an overview of the current knowledge state of neurovascular coupling and discuss seizure-related alterations in neurovascular coupling and CBF control.

The research efforts reported here are aimed at experimentally investigating the effects of incorporating steel fibres, with various dosages, on the shear capacity and shear behaviour characteristics of reinforced concrete deep beams. The primary experimental results obtained during this research, as well as an extensive secondary dataset, were used to examine and verify a proposed new model by the authors for calculating the shear resistance of steel fibres reinforced concrete (SFRC) deep beams. The experimental investigation involved 12 deep beams with four fibres dosages, namely: 0, 30, 40, and 65 kg/m3 and three stirrup ratios, namely: 0.1%, 0.15%, and 0.25%. The experimental results have shown that steel fibres improved the shear resistance of the deep beams (up to 55%), decreased the shear crack width (up to 68%), reduced the displacement of the beams (up to 57%), and enhanced the deformation capacity of the beams (up to 45%). The authors propose a new semi-empirical formula for estimation of the shear resistance of SFRC deep beams. The accuracy of the formula was evaluated using 116 beams dataset including a primary dataset obtained during this project as well as the published secondary dataset. The reliability and accuracy of the proposed formula were compared with other four published formulas. It is evident that the newly proposed formula increases the accuracy and reliability of the estimation of the shear resistance of SFRC deep beams when compared to the previously published models.

Background This study was conducted in order to develop a model for predicting response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) using pretreatment quantitative ultrasound (QUS) radiomics. Methods This was a multicenter study involving four sites across North America, and appropriate approval was obtained from the individual ethics committees. Eighty‐two patients with LABC were included for final analysis. Primary tumors were scanned using a clinical ultrasound system before NAC was started. The tumors were contoured, and radiofrequency data were acquired and processed from whole tumor regions of interest. QUS spectral parameters were derived from the normalized power spectrum, and texture analysis was performed based on six QUS features using a gray level co‐occurrence matrix. Patients were divided into responder or nonresponder classes based on their clinical‐pathological response. Classification analysis was performed using machine learning algorithms, which were trained to optimize classification accuracy. Cross‐validation was performed using a leave‐one‐out cross‐validation method. Results Based on the clinical outcomes of NAC treatment, there were 48 responders and 34 nonresponders. A K‐nearest neighbors (K‐NN) approach resulted in the best classifier performance, with a sensitivity of 91%, a specificity of 83%, and an accuracy of 87%. Conclusion QUS‐based radiomics can predict response to NAC based on pretreatment features with acceptable accuracy., This multi‐institutional study investigated the role of radiomics from quantitative ultrasound (QUS) in predicting the final response to neoadjuvant chemotherapy (NAC) for 82 patients with locally advanced breast cancer (LABC). We had shown the QUS‐radiomics model can predict the response to treatment with an accuracy of 87% from spectroscopic features obtained before the start of NAC.

INTRODUCTION: Quantitative ultrasound parameters based on form factor models were investigated as potential biomarkers of cell death in breast tumor (MDA-231) xenografts treated with chemotherapy. METHODS: Ultrasound backscatter radiofrequency data were acquired from MDA-231 breast cancer tumor–bearing mice (n = 20) before and after the administration of chemotherapy drugs at two ultrasound frequencies: 7 MHz and 20 MHz. Radiofrequency spectral analysis involved estimating the backscatter coefficient from regions of interest in the center of the tumor, to which form factor models were fitted, resulting in estimates of average scatterer diameter and average acoustic concentration (AAC). RESULTS: The ∆AAC parameter extracted from the spherical Gaussian model was found to be the most effective cell death biomarker (at the lower frequency range, r2 = 0.40). At both frequencies, AAC in the treated tumors increased significantly (P = .026 and .035 at low and high frequencies, respectively) 24 hours after treatment compared with control tumors. Furthermore, stepwise multiple linear regression analysis of the low-frequency data revealed that a multiparameter quantitative ultrasound model was strongly correlated to cell death determined histologically posttreatment (r2 = 0.74). CONCLUSION: The Gaussian form factor model–based scattering parameters can potentially be used to track the extent of cell death at clinically relevant frequencies (7 MHz). The 20-MHz results agreed with previous findings in which parameters related to the backscatter intensity (i.e., AAC) increased with cell death. The findings suggested that, in addition to the backscatter coefficient parameter ∆AAC, biological features including tumor heterogeneity and initial tumor volume were important factors in the prediction of cell death response.

BACKGROUND: Conventional frequency quantitative ultrasound in conjunction with textural analysis techniques was investigated to monitor noninvasively the effects of cancer therapies in an in vivo preclinical model. METHODS: Conventional low-frequency (∼7 MHz) and high-frequency (∼20 MHz) ultrasound was used with spectral analysis, coupled with textural analysis on spectral parametric maps, obtained from xenograft tumor-bearing animals (n = 20) treated with chemotherapy to extract noninvasive biomarkers of treatment response. RESULTS: Results indicated statistically significant differences in quantitative ultrasound-based biomarkers in both low- and high-frequency ranges between untreated and treated tumors 12 to 24 hours after treatment. Results of regression analysis indicated a high level of correlation between quantitative ultrasound-based biomarkers and tumor cell death estimates from histologic analysis. Applying textural characterization to the spectral parametric maps resulted in an even stronger correlation (r2 = 0.97). CONCLUSION: The results obtained in this research demonstrate that quantitative ultrasound at a clinically relevant frequency can monitor tissue changes in vivo in response to cancer treatment administration. Using higher order textural information extracted from quantitative ultrasound spectral parametric maps provides more information at a high sensitivity related to tumor cell death.

Background Breast cancer is the most common cancer among women worldwide and the second leading cause of brain metastases (BrM). We assessed the treatment patterns and outcomes of women treated for breast cancer BrM at our institution in the modern era of stereotactic radiosurgery (SRS). Materials and Methods We conducted a retrospective analysis of women (≥18 years of age) with metastatic breast cancer who were treated with surgery, whole brain radiotherapy (WBRT), or SRS to the brain at the Sunnybrook Odette Cancer Centre, Toronto, Canada, between 2008 and 2018. Patients with a history of other malignancies and those with an uncertain date of diagnosis of BrM were excluded. Descriptive statistics were generated and survival analyses were performed with subgroup analyses by breast cancer subtype. Results Among 683 eligible patients, 153 (22.4%) had triple-negative breast cancer, 188 (27.5%) had HER2+, 246 (36.0%) had hormone receptor (HR)+/HER2−, and 61 (13.3%) had breast cancer of an unknown subtype. The majority of patients received first-line WBRT (n = 459, 67.2%) or SRS (n = 126, 18.4%). The median brain-specific progression-free survival and median overall survival (OS) were 4.1 months (interquartile range [IQR] 1.0–9.6 months) and 5.1 months (IQR 2.0–11.7 months) in the overall patent population, respectively. Age >60 years, presence of neurological symptoms at BrM diagnosis, first-line WBRT, and HER2− subtype were independently prognostic for shorter OS. Conclusion Despite the use of SRS, outcomes among patients with breast cancer BrM remain poor. Strategies for early detection of BrM and central nervous system–active systemic therapies warrant further investigation. Implications for Practice Although triple-negative breast cancer and HER2+ breast cancer have a predilection for metastasis to the central nervous system (CNS), patients with hormone receptor–positive/HER2− breast cancer represent a high proportion of patients with breast cancer brain metastases (BrM). Hence, clinical trials should include patients with BrM and evaluate CNS-specific activity of novel systemic therapies when feasible, irrespective of breast cancer subtype. In addition, given that symptomatic BrM are associated with shorter survival, this study suggests that screening programs for the early detection and treatment of breast cancer BrM warrant further investigation in an era of minimally toxic stereotactic radiosurgery.

Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18–21 and are established driver mutations in non-small cell lung cancer (NSCLC)1–3. Targeted therapies are approved for patients with ‘classical’ mutations and a small number of other mutations4–6. However, effective therapies have not been identified for additional EGFR mutations. Furthermore, the frequency and effects of atypical EGFR mutations on drug sensitivity are unknown1,3,7–10. Here we characterize the mutational landscape in 16,715 patients with EGFR-mutant NSCLC, and establish the structure–function relationship of EGFR mutations on drug sensitivity. We found that EGFR mutations can be separated into four distinct subgroups on the basis of sensitivity and structural changes that retrospectively predict patient outcomes following treatment with EGFR inhibitors better than traditional exon-based groups. Together, these data delineate a structure-based approach for defining functional groups of EGFR mutations that can effectively guide treatment and clinical trial choices for patients with EGFR-mutant NSCLC and suggest that a structure–function-based approach may improve the prediction of drug sensitivity to targeted therapies in oncogenes with diverse mutations.

In this paper, a low-cost prototype for humanoid robotic arm that is controlled by either voice, gesture or brain signals is introduced. The prototype consists of a robotic arm that can rotate around a vertical axis and a hand with five fingers, which animates approximately the movements of a human hand. This model can be operated by brainwave signals from a Neurosky MindWaveTM Mobile 2 Brainwave Sensing Headset, by human gesture using Leap Motion device, by voice command using Google Assistant, or by web-based interface. All operations can be monitored by a user interface on web server, with the support from a Raspberry Pi board. The experiments show that the average accuracy of our mindwave control prototype is about 83%, which is similar to most of previous high-cost solutions, and can go up to nearly 100% for the case that the data acquisition time is larger than 10 s (which improves 2–8% compared to previous works). This model would be highly useful in practice, especially, for people with disabilities who cannot use their hands, as well as in academia when it is used for undergraduate students’ experiments on robotics.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare condition characterized by abnormal involuntary movements that are precipitated by a sudden movement. PKD is often misdiagnosed with psychogenic movement disorders. Carbamazepine is usually the first choice of medication due to its well-established evidence but could induce Stevens-Johnson syndrome. We report a 21-year-old male patient with PKD referred to our movement disorders clinic after being misdiagnosed with conversion syndrome. PRRT2 gene testing using next-generation sequencing revealed a mutation in c.649dupC p. (Arg217fs). The patient responded well to carbamazepine but had to withdraw the treatment due to carbamazepine-induced Stevens-Johnson syndrome after 3 weeks of medication. Our patient did not respond to trials of levetiracetam and phenytoin but finally responded well to oxcarbazepine. The patient was followed up for 4 years, during which he had no attacks and no side effects. Here, we present a PKD case with carbamazepine-induced Stevens-Johnson syndrome successfully treated with oxcarbazepine despite the risk of cross-reactive skin eruption between these antiepileptics. Careful history taking and examining patient’s attacks are crucial to accurate diagnosis and treatment in PKD patients.

Survivorship care plans (SCPs) are recommended to promote appropriate follow-up care, but implementation has been limited. We conducted a randomized controlled trial comparing three SCP delivery models in two health systems. We utilize mixed methods to compare the feasibility and participants’ perceived value of the three models. Patients completing treatment for stage I–III breast, prostate, or colorectal cancer from one urban-academic and one rural community cancer center were randomized to (1) mailed SCP, (2) SCP delivered during an in-person survivorship visit, or (3) SCP delivered during an in-person survivorship visit plus 6-month follow-up. Clinics had flexibility in intervention implementation. Quantitative data summarize intervention fidelity and protocol deviations. Qualitative interview data provide patients’ perspectives on feasibility and intervention value. Of 475 eligible participants approached, 378 (79%) were randomized. Of 345 SCPs delivered, 265 (76.8%) were by protocol. Protocol deviations were more common at the urban-academic center. In post-study qualitative interviews, participants recalled little about the SCP document or visit(s). SCPs were valued for information and care coordination, although their static nature was limiting, and sometimes SCP information differed from that provided elsewhere. Visits were opportunities for care and reassurance, but time and distance to the clinic were barriers. SCP provision was challenging. Patients were interested in SCP, but not necessarily additional survivorship visits, particularly at the urban-academic hospital. These findings suggest that patients value careful consideration of health care needs during the transition out of treatment; SCP documents are one element of this. For many patients, models without additional visits and dynamic SCPs may be preferred.

Oligometastatic disease was originally defined by Hellman and Weichselbaum as an intermediate-state existing between locally confined and widely disseminated malignancy, whose natural history could be positively impacted with systemic and importantly local therapies such as radiation. Currently oligometastatic prostate cancer (OPCa) is defined clinically by lesion enumeration and several subgroups exist: de novo (synchronous) oligometastatic disease present at initial diagnosis, oligorecurrent (metachronous) disease arising after definitive therapy to the prostate, and oligoprogressive disease where isolated lesions progress in a background of otherwise stable disease. In this review we highlight current knowledge and the potential future of local therapies, such as radiation to the primary prostate and metastasis-directed therapy (MDT), in the disease management of OPCa for all three subgroups. In addition, we examine more recent studies classifying the patterns of failure and natural history of OPCa following treatment with local therapies. Finally, while current clinical definitions of OPCa dominate, we introduce studies attempting to elucidate a more biological definition of OPCa to allow for improved selection of patients to treat with local therapies and to better inform precision combination approaches with systemic therapy.

Power supply design is perhaps the most challenging aspect of the entire process of controlling noise and radiation in high-speed DSP design. This is largely because of the complexity of the dynamic load switching conditions. These include the DSP going into or out of low power modes, excessive in-rush current due to bus contention and charging decoupling capacitors, large voltage droop due to inadequate decoupling and layout, oscillations that overload the linear regulator output, and high current switching noise generated by switching voltage regulators. A clean and stable power supply design is required for all DSP systems to guarantee system stability. This chapter outlines the importance of proper power supply design and the methods to minimize unwanted noise.

Assessment of measurable residual disease (often referred to as “minimal residual disease”) has emerged as a highly sensitive indicator of disease burden during and at the end of treatment and has been correlated with time-to-event outcomes in chronic lymphocytic leukemia. Undetectable-measurable residual disease status at the end of treatment demonstrated independent prognostic significance in chronic lymphocytic leukemia, correlating with favorable progression-free and overall survival with chemoimmunotherapy. Given its utility in evaluating depth of response, determining measurable residual disease status is now a focus of outcomes in chronic lymphocytic leukemia clinical trials. Increased adoption of measurable residual disease assessment calls for standards for nomenclature and outcomes data reporting. In addition, many basic questions have not been systematically addressed. Here, we present the work of an international, multidisciplinary, 174-member panel convened to identify critical questions on key issues pertaining to measurable residual disease in chronic lymphocytic leukemia, review evaluable data, develop unified answers in conjunction with local expert input, and provide recommendations for future studies. Recommendations are presented regarding methodology for measurable residual disease determination, assay requirements and in which tissue to assess measurable residual disease, timing and frequency of assessment, use of measurable residual disease in clinical practice versus clinical trials, and the future usefulness of measurable residual disease assessment. Nomenclature is also proposed. Adoption of these recommendations will work toward standardizing data acquisition and interpretation in future studies with new treatments with the ultimate objective of improving outcomes and curing chronic lymphocytic leukemia.

Background The traumatic dislocation of the radial head in children is commonly treated by closed reduction. Sometimes, however, this strategy of treatment may not be effective due to the location of soft tissues in the radio‐shoulder joint. The literature presents a few cases of the irreducible radial head dislocation with ulnar plastic deformation. Because it is a relatively rare condition, such a traumatic dislocation can be easily missed. Neglected injuries can lead to unwanted complications and unpredictable surgical outcomes. Case presentation This study presents a relatively rare case of traumatic radial head dislocation with ulnar plastic deformation in a 3‐year‐old child, which was successfully treated by open reduction. The examined case did not require osteotomy and ligamentous reconstruction. The initial attempt of closed reduction failed due to annular ligament interposition, which has been detected on MRI. After 3 months of treatment, the range of motion of the operated arm gradually improved. At the 6‐month follow‐up, the Mayo elbow‐performance score indicated an excellent treatment outcome. Conclusions The delayed treatment of radial head dislocation with ulnar plastic deformation can hinder the supination and pronation of the forearm, resulting in elbow/forearm deformity. The earlier this condition is detected, the easier it will be to treat it and the better the treatment outcome will be. The examined case of irreversible traumatic dislocation, successfully treated by open reduction, may help to treat radial head dislocation better., Traumatic radial head dislocation with ulnar plastic deformation is very rare. These neglected traumas resulted in a far more complex injury. Here is a rare case of injury in a 3‐year‐old child that was successfully treated. The initial close‐reduction attempt was fail due to annular ligament interposition. Delayed treatment can lead to deformity of elbow and forearm.

Despite the low contribution of heavy ions to the total fluence in the space radiation environment, their radiobiological effect on the human body is extremely high. In this article, we investigated the radiation field which resulted from the interaction of galactic cosmic rays (GCRs), specifically some heavy ions and energies, typically encountered in space with a realistic multilayer sample of the International Space Station (ISS) Columbus module’s shielding wall. The quality factor, Q, and the normalized dose equivalent, H, derived from microdosimetric measurements for C, Ne, and Si ions behind different spacecraft wall configurations and materials are presented in this article. Particularly, carbon fiber, polyoxymethylene, and perspex with same areal density compared to currently used aluminum were investigated.

The hexosamine biosynthetic pathway (HBP) is a glucose metabolism pathway that results in the synthesis of a nucleotide sugar UDP-GlcNAc, which is subsequently used for the post-translational modification (O-GlcNAcylation) of intracellular proteins that regulate nutrient sensing and stress response. The HBP is carried out by a series of enzymes, many of which have been extensively implicated in cancer pathophysiology. Increasing evidence suggests that elevated activation of the HBP may act as a cancer biomarker. Inhibition of HBP enzymes could suppress tumor cell growth, modulate the immune response, reduce resistance, and sensitize tumor cells to conventional cancer therapy. Therefore, targeting the HBP may serve as a novel strategy for treating cancer patients. Here, we review the current findings on the significance of HBP enzymes in various cancers and discuss future approaches for exploiting HBP inhibition for cancer treatment.

Antiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

Asphalt concrete (AC) is a commonly used material in road construction; however, its quality is highly dependent on atmosphere temperature. Temperatures can adversely affect AC performance and its service life. This paper presents an empirical model to predict the heat distribution in AC in Danang. A temperature monitoring station has been set up at the University of Danang—University of Science and Technology to monitor heat distribution in the pavement. The monitored AC layer with a thickness of 13 cm was constructed on a 15 cm cement-treated base. Thermocouple sensors were then installed in AC at different depths of 2, 5, 7, 10, and 12 cm from the pavement surface. The temperature was monitored continuously for five days in September, 2020. Climate data, including air temperature and solar radiation intensity, was collected from the Vietnamese National Centre for Hydro-meteorological Forecasting. Statistical models delivered from the collected data to predict the temperature distribution in AC were developed. They were finally compared with previous studies and suited to predict the temperature distribution in AC in Danang city.

Cellulose microfibers were successfully fabricated from Vietnamese Nipa palm by mechanical and chemical treatments. The Nipa palm petioles were simply rolled, pressed, and separated. They were then pretreated with an alkaline solution and submitted to acid hydrolysis to remove the impurities (tCell). The microfibers were reinforced with reduced graphene oxide to form a hybrid that was reduced with hydrazine hydrate in the last stage (tCell-rGO). The structure and properties of tCell and tCell-rGO were evaluated by FTIR, XRD, DSC, TGA, SEM, BET, and the sheet resistance. It was observed that the treated cellulose microfibers exhibited a diameter of 10–20 μm and had good crystallinity in the structure. Both tCell and tCell-rGO exhibited low-density values of 1.52 kg/m3 and 0.58 kg/m3, respectively, and had good specific surface area values of 11.2 m2/g and 13.0 m2/g, respectively. These results supported the decrease in the density and the increase in the specific surface area of the tCell-rGO samples in comparison with the tCell. The existence of rGO sheets in the cellulose microfiber matrix resulted in changes in the structure, arrangement, and crystallization of pristine microfibers. The thermal property and electrical conductivity of the reinforced GO cellulose microfibers were significantly improved. rGO not only showed its role as a surface modification agent that helps the cellulose microfibers disperse better in the non-polar substrate, but also contributed to the increase of the heat-stable and mechanical properties of polymer. The thermal stability of tCell-rGO/PMMA composite was notably improved more than 40°C in maximum decomposition temperature by an emulsion polymerization technique. The material based on cellulose microfibers from the Vietnamese Nipa palm tree and reduced graphene oxide overcame some disadvantages such as the poor heat resistance, poor dispersion of the original fibers in the non-polar polymer and displayed great potential for environmentally friendly future applications.

BACKGROUND T2 * mapping has proven useful in tendon research and may have the ability to detect subtle changes at an early stage of tendinopathy. PURPOSE To investigate the difference in T2 * between patients with early tendinopathy and healthy controls, and to investigate the relationship between T2 * and clinical outcomes, tendon size, and mechanical properties. STUDY TYPE Prospective cross-sectional. SUBJECTS Sixty-five patients with early tendinopathy and 25 healthy controls. FIELD STRENGTH/SEQUENCE Three Tesla, ultrashort time to echo magnetic resonance imaging. ASSESSMENT Tendon T2 * was quantified using a monoexponential fitting algorithm. Clinical symptoms were evaluated using the Victorian Institute of Sports Assessment-Achilles/Patella (VISA-A/VISA-P). In vivo mechanical properties were measured using an ultrasound-based method that determined force and deformation simultaneously in tendons of patellar tendinopathy patients. STATISTICAL TESTS A generalized linear model adjusted for age was applied to investigate the difference between patients and controls. In the two patient groups, linear regressions were applied to investigate the association between T2 * and tendon size, clinical outcomes, and biomechanical properties. RESULTS There was a significant difference in T2 * between patients and healthy controls (204.8 [95% CI: 44.5-365.0] μsec, P

ispartof: BLOOD vol:137 issue:8 pages:1117-1120 ispartof: location:United States status: published

Objective The hepatitis C virus (HCV) is the most common blood-borne infection in the United States. Although 2% to 3% of the global population is estimated to be infected with HCV, an estimated 18% of the US prison population may be infected. The objective of this study was to establish an epidemiologic profile of HCV infection in the largest urban jail system in the United States. Methods We retrospectively analyzed 20 years of data on demographic characteristics, risk factors, and HCV positivity among 80 681 individuals incarcerated at the Los Angeles County Jail who were tested for HCV infection from January 1, 2000, through December 31, 2019. We used multivariate logistic regression analysis to determine predictors of HCV positivity. Results Of the 80 681 individuals tested, 27 881 (34.6%) had positive test results for HCV infection. In the multivariate analysis, HCV positivity was most strongly associated with injection drug use (adjusted odds ratio [aOR] = 34.9; 95% CI, 24.6-49.5) and being born during 1946-1955 (aOR = 13.0; 95% CI, 11.9-14.2). Men were more likely than women to have HCV infection (aOR = 1.4; 95% CI, 1.3-1.5), and Hispanic (aOR = 4.2; 95% CI, 3.9-4.4) and non-Hispanic White (aOR = 3.8; 95% CI, 3.5-4.0) individuals were more likely than non-Hispanic African American individuals to have HCV infection. Noninjection drug use, homelessness, and mental health issues were also significantly associated with HCV positivity. Conclusion Even in the absence of resources for universal screening for HCV infection, the creation of a risk profile and its implementation into a screening program may be a beneficial first step toward improving HCV surveillance and establishing an accurate estimate of HCV infection in the incarcerated population.

Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC. Neoadjuvant treatment with nivolumab plus ipilimumab is well tolerated and demonstrates clinical efficacy in patients with early stage lung cancer.

Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) is associated with improved survival outcomes among women with HER2 positive (HER2+) breast cancer. We aimed to analyze the clinical, pathological and molecular factors associated with pCR in our series of HER2+ breast cancer patients. Methods: Between 2009 and 2019, breast cancer patients receiving NAC at our centre were enrolled in a prospective database. For this study we selected women with HER2+ unilateral breast cancer stages II or III who received anthracycline-taxane NAC regimens (with trastuzumab given concurrently with the taxane) and subsequently underwent breast and axillary surgery with curative intent. Medical charts of these 161 women were retrospectively reviewed to determine what clinical, pathological and molecular characteristics were associated with pCR using bivariate and multivariate analysis. Results: Of the 161 HER2+ women median age at diagnosis was 49 years (range 25-78) with 90 (56%) women under age 50. Total of 104 (65%) tumors were stage II, 108 (67%) expressed estrogen and/or progesterone receptors, 139 (86%) had HER2 3+ expression by immunohistochemistry (IHC) and 22 (14%) had HER2 IHC 2+ expression with amplified HER2 on fluorescence in situ hybridization (FISH) test. The NAC regimens were: Doxorubicin-Cyclophosphamide-Paclitaxel for 83 (52%) and Fluorouracil-Epirubicin-Cyclophosphamide-Docetaxel for 78 (48%) women. A total of 73 patients [45%; 44/108 HR+ (41%) and 29/53 HR- (55%)] achieved pCR (p=0.94). pCR rate among HER2 IHC 3+ tumors was 69/139 (50%), while for HER2 IHC 2+ tumors was 4/22 (18%). On bivariate analysis HER2 IHC 3+, absence of estrogen receptors and absence of progesterone receptors were predictive of pCR, while age, menopausal status, histologic subtype, tumor grade and NAC regimen were not. In the multivariate model only HER2 IHC 3+ expression remained a significant predictor of pCR (OR =4.443, 95% CI 1.376 - 14.344). Conclusion: Our analysis suggests that for HER2+ breast cancers treated with NAC with anthracycline-taxane and trastuzumab, HER2 IHC 3+ expression is associated with a higher rate of pCR compared to HER2 IHC 2+ expression with FISH amplification. Further analysis in a larger cohort is warranted. Citation Format: Neda Stjepanovic, Katarzyna Jerzak, Maureen Trudeau, Andrea Eisen, Sonal Gandhi, Ellen Warner, Danilo Giffoni MM Mata, Anthony Lott, Maria Romero, Sharon Lemon-Wong, Althea VanMassop, Xingshan Cao, William Tran, Rossanna Pezo. Analysis of factors associated with pathological complete response (pCR) in patients with HER2+ breast cancer receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-33.

Gastric cancer is a rare long-term complication in gastrocystoplasty. We report 2 cases of gastric adenocarcinoma and review the literature for similar cases. A total of 14 cases are identified. The majority of patients are males, presented with hematuria, and developed cancer at a younger age, more than 10 years after gastrocystoplasty. Long-term follow up information was limited, but 5 patients (36%) died within 5 years of diagnosis. Annual surveillance for malignancy may not be effective due to its rarity. However, symptomatic patients, particularly those 10 years after the surgery, warrant detailed evaluation to rule out neoplastic transformation.

This paper designs a 1 × 2 switchable dual-mode optical 90° hybrid device on the silicon-on-insulator (SOI) platform for the mode division multiplexing hybridized coherent transmission systems in optical communication. Our proposed hybrid uses various 2 × 2 multimode interference (MMI) couplers, symmetric Y-junctions, and thermo-optic phase shifters. The suggested hybrid device working principle is proved on theoretical analysis about the multimode interference and the transfer matrix relation. The optimization of geometrical parameters and metallic micro-heaters is executed through the numerical simulation method. The proposed hybrid coupler expresses lots of optical performance advantages, with an insertion loss lower than 2.5 dB, a common-mode rejection ratio (CMRR) better than −24 dB, and phase error smaller than 4° in the 50-nm wavelength bandwidth of the third telecom window for both two TE modes. Besides, the device is proven large geometrical tolerances in terms of width and height tolerances larger than ±50 nm and ±6 nm in the 1.5-dB variation limit of transmission, respectively. In addition, the proposed device attains relatively low power consumption under 75 mW and an ultrafast switching time below 10 μs. Such advantages of good performances make the device a promising potential for broadband and intra-chip MDM-hybridized coherent optical communication systems and photonic integrated circuits.

Neoadjuvant chemotherapy (NAC) is used to treat patients with high-risk breast cancer. The tumor response to NAC can be classified as either a pathological partial response (pPR) or pathological complete response (pCR), defined as complete eradication of invasive tumor cells, with a pCR conferring a significantly lower risk of recurrence. Predicting the response to NAC, however, remains a significant clinical challenge. The objective of this study was to determine if analysis of nuclear features on core biopsies using artificial intelligence (AI) can predict response to NAC. Fifty-eight HER2-positive or triple-negative breast cancer patients were included in this study (pCR n = 37, pPR n = 21). Multiple deep convolutional neural networks were developed to automate tumor detection and nuclear segmentation. Nuclear count, area, and circularity, as well as image-based first- and second-order features including mean pixel intensity and correlation of the gray-level co-occurrence matrix (GLCM-COR) were determined. In univariate analysis, the pCR group had fewer multifocal/multicentric tumors, higher nuclear intensity, and lower GLCM-COR compared to the pPR group. In multivariate binary logistic regression, tumor multifocality/multicentricity (OR = 0.14, p = 0.012), nuclear intensity (OR = 1.23, p = 0.018), and GLCM-COR (OR = 0.96, p = 0.043) were each independently associated with likelihood of achieving a pCR, and the model was able to successful classify 79% of cases (62% for pPR and 89% for pCR). Analysis of tumor nuclear features using digital pathology/AI can significantly improve models to predict pathological response to NAC.

Purpose We develop a multi-centric response predictive model using QUS spectral parametric imaging and novel texture-derivate methods for determining tumour responses to neoadjuvant chemotherapy (NAC) prior to therapy initiation. Materials and methods QUS Spectroscopy provided parametric images of mid-band-fit (MBF), spectral-slope (SS), spectral-intercept (SI), average-scatterer-diameter (ASD), and average-acoustic-concentration (AAC) in 78 patients with locally advanced breast cancer (LABC) undergoing NAC. Ultrasound radiofrequency data were collected from Sunnybrook Health Sciences Center (SHSC), University of Texas MD Anderson Cancer Center (MD-ACC), and St. Michaels Hospital (SMH) using two different systems. Texture analysis was used to quantify heterogeneities of QUS parametric images. Further, a second-pass texture analysis was applied to obtain texture-derivate features. QUS, texture- and texture-derivate parameters were determined from both tumour core and a 5-mm tumour margin and were used in comparison to histopathological analysis for developing a response predictive model to classify responders versus non-responders. Model performance was assessed using leave-one-out cross-validation. Three standard classification algorithms including a linear discriminant analysis (LDA), k-nearest-neighbors (KNN), and support vector machines-radial basis function (SVM-RBF) were evaluated. Results A combination of tumour core and margin classification resulted in a peak response prediction performance of 88% sensitivity, 78% specificity, 84% accuracy, 0.86 AUC, 84% PPV, and 83% NPV, achieved using the SVM-RBF classification algorithm. Other parameters and classifiers performed less well running from 66% to 80% accuracy. Conclusions A QUS-based framework and novel texture-derivative method enabled accurate prediction of responses to NAC. Multi-centric response predictive model provides indications of the robustness of the approach to variations due to different ultrasound systems and acquisition parameters.

Cancer metastasis is the leading cause of cancer-related mortality, and most patients with metastases from solid tumors have historically been considered incurable. Here, we discuss the evolution of our understanding of the oligometastatic state with an emphasis on the view that cancer metastasis represents a spectrum of disease. We highlight several recently published prospective clinical trials demonstrating improvements in cancer-specific outcomes with the utilization of metastasis-directed local therapies. We discuss biological aspects of oligometastases, including genetic, epigenetic, and immune determinants of the metastatic spectrum. Finally, we propose future considerations regarding clinical trial design for patients with oligometastatic disease.

There are limited data to guide the use of anticoagulation in cirrhotic patients prior to liver transplantation especially when using direct oral anticoagulants. In this article, we present 2 cases. The first is a 42-year-old male with cirrhosis complicated by portal vein thrombosis (PVT) treated with dabigatran who underwent orthotopic liver transplantation without complication. The second case is a 65-year-old man with alcoholic cirrhosis complicated by PVT treated with dabigatran who underwent orthotopic liver transplantation and required reoperation for surgical bleeding. Both patients were treated with dabigatran’s reversal agent idarucizumab prior to incision. In this case series, we discuss the treatment of cirrhotic patients with various anticoagulants, considerations for anticoagulant selection and reversal prior to liver transplant, and questions for future investigation.

Background As the transgender and gender non-conforming (TGNC) population in the United States continues to grow, there is a need for health care providers who are competent in managing gender-affirming therapy (GAT) for these individuals. Objectives The purpose of this study was to assess practicing pharmacists’ readiness to care for transgender and gender nonconforming (TGNC) patients and to compare the perceptions between pharmacists who have received formal education about gender-affirming therapy (GAT) and those who have not received such training. Methods This was a cross-sectional study that was conducted online over 4 weeks (January 2019-February 2019). A survey was distributed to pharmacists in the United States. Distribution of the survey was conducted through professional pharmacy social media groups. Respondents were asked to anonymously rate their perceived preparedness to care for a TGNC patient and to disclose any formal GAT training they had received during pharmacy school or through continuing pharmacy education. Responses were further stratified on the basis of self-reported completion of GAT education taken after pharmacy school. The responses of those who had received GAT training were compared with the responses of those who had not received GAT training. Results The results of this survey indicated that few pharmacists felt prepared to care for TGNC patients. Furthermore, few pharmacists report receiving formal education over GAT during pharmacy school or postgraduation. Approximately 41% and 40% of respondents, respectively, reported that they did not feel prepared to make recommendations to other health care providers on GAT and counsel TGNC patients about GAT regimens. However, the self-reported GAT-trained pharmacists showed a significantly increased level of perceived preparedness in caring for TGNC patients when compared with pharmacists who did not receive such education. Conclusion Increased accessibility to GAT education for pharmacists may be associated with a significant growth in pharmacists’ perceived ability to provide care for and interact with transgender patients.

Introduction The combination of programmed cell death protein-1 or programmed death-ligand 1 immune checkpoint blockade and chemotherapy has revolutionized the treatment of advanced NSCLC, but the mechanisms underlying this synergy remain incompletely understood. In this study, we explored the relationships between neoadjuvant chemotherapy and the immune microenvironment (IME) of resectable NSCLC to identify novel mechanisms by which chemotherapy may enhance the effect of immune checkpoint blockade. Methods Genomic, transcriptomic, and immune profiling data of 511 patients treated with neoadjuvant chemotherapy followed by surgery (NCT) versus upfront surgery (US) were compared with determined differential characteristics of the IMEs derived from whole-exome sequencing (NCT = 18; US = 73), RNA microarray (NCT = 45; US = 202), flow cytometry (NCT = 17; US = 39), multiplex immunofluorescence (NCT = 10; US = 72), T-cell receptor sequencing (NCT = 16 and US = 63), and circulating cytokines (NCT = 18; US = 73). Results NCT was associated with increased infiltration of cytotoxic CD8+ T cells and CD20+ B cells. Moreover, NCT was associated with increases in CD8+CD103+ and CD4+CD103+PD-1+TIM3− tissue resident memory T cells. Gene expression profiling supported memory function of CD8+ and CD4+ T cells. However, NCT did not affect T-cell receptor clonality, richness, or tumor mutational burden. Finally, NCT was associated with decreased plasma BDNF (TrkB) at baseline and week 4 after surgery. Conclusions Our study supports that, in the context of resectable NSCLC, neoadjuvant chemotherapy promotes antitumor immunity through T and B cell recruitment in the IME and through a phenotypic change toward cytotoxic and memory CD8+ and CD4+ memory helper T cells.

Purpose of Review This review highlights the applications of point-of-care ultrasound in low- and middle-income countries and shows the diversity of ultrasound in the diagnosis and management of patients. Recent Findings There is a paucity of data on point-of-care ultrasound in anesthesiology in low- and middle-income countries. However, research has shown that point-of-care ultrasound can effectively help manage infectious diseases, as well as abdominal and pulmonary pathologies. Summary Point-of-care ultrasound is a low-cost imaging modality that can be used for the diagnosis and management of diseases that affect low- and middle-income countries. There is limited data on the use of ultrasound in anesthesiology, which provides clinicians and researchers opportunity to study its use during the perioperative period.

Objective We calculated the short- and long-term care resource use and costs in adults with high-risk conditions for cardiovascular disease (HRCVD) as defined by the Canadian Cardiovascular Society dyslipidemia guidelines. Methods We linked Alberta health databases to identify patients aged ≥ 18 years with HRCVD between fiscal year (FY) 2012 and FY2016. The first HRCVD event was the index event. Patients were categorized into (1) primary prevention patients and (2) secondary prevention patients at the index event and were followed until death, they moved out of the province, or they were censored at March 2018. We calculated the resource use and costs for each of the 5 years after the index event. Results The study included 459,739 HRCVD patients (13,947 [3%] were secondary prevention patients). The secondary prevention patients were older (median age 61 years vs. 55 years; p < 0.001), and there were fewer females in this group (30.4% vs. 51.3%; p < 0.001). The total healthcare costs in the first year decreased over time (FY2012: 1.16 billion Canadian dollars (CA$); FY2016: CA$1.05 billion; p < 0.001). An HRCVD patient incurred CA$12,068, CA$5626, and CA$4655 during the first, second, and fifth year, respectively (p for trend