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The Committee for Infection Control in the Emergency Department and the Joint Working Group undertook a comprehensive and multifaceted review of infection control measures for emergency outpatients and related matters, and released a checklist for infection control in emergency departments. This checklist includes a control system for infection control, education, screening, and vaccination, prompt response to suspected infections, and management of the risk of infection in facilities. In addition, the timing of the check and interval at which the check is carried out are specified as categories., The risk of encountering human‐to‐human infections, including emerging infectious diseases, should be adequately and appropriately addressed in the emergency department. However, guidelines based on sufficient evidence on infection control in the emergency department have not been developed anywhere in the world. Each facility examines and implements its own countermeasures. The Japanese Association for Acute Medicine has established the “Committee for Infection Control in the Emergency Department” in cooperation with the Japanese Association for Infectious Diseases, Japanese Society for Infection Prevention and Control, Japanese Society for Emergency Medicine, and Japanese Society for Clinical Microbiology. A joint working group has been established to consider appropriate measures. This group undertook a comprehensive and multifaceted review of infection control measures for emergency outpatients and related matters, and released a checklist for infection control in emergency departments. This checklist has been prepared such that even small emergency departments with few or no emergency physicians can control infection by following the checklist, without committing any major errors. The checklist includes a control system for infection control, education, screening, and vaccination, prompt response to suspected infections, and management of the risk of infection in facilities. In addition, the timing of the check and interval at which the check is carried out are specified as categories. We hope that this checklist will contribute to improving infection control in the emergency department.

Some macrolides such as 14- and 15-membered macrolides have immunomodulatory effects such as suppression of mucin overproduction. Because a novel macrolide, solithromycin, was developed, we examined whether it suppresses the overexpression of mucin in vitro. A human airway epithelial cell line NCI–H292 was stimulated by Pseudomonas aeruginosa lipopolysaccharides to induce the overproduction of a major mucin, MUC5AC. Treatment with 10 μg/mL of solithromycin significantly inhibited LPS-induced MUC5AC in both mRNA and protein levels as well as a 15-membered macrolide, azithromycin. These findings support that solithromycin has a potential immunomodulatory effect.

Previous studies in animals and humans suggest the periaqueductal grey region (PAG) is a final integration station between the brain and laryngeal musculature during phonation. To date, a limited number of functional magnetic neuroimaging (fMRI) studies have examined the functional connectivity of the PAG during volitional human phonation. An event-related, stimulus-induced, volitional movement paradigm was used to examine neural activity during sustained vocalization in neurologically healthy adults and was compared to controlled exhalation through the nose. The contrast of vocalization greater than controlled expiration revealed activation of bilateral auditory cortex, dorsal and ventral laryngeal motor areas (dLMA and vLMA) (p 0.05, corrected), and suggested activation of the cerbellum, insula, dorsomedial prefrontal cortex (dmPFC), amygdala, and PAG. The functionally defined PAG cluster was used as a seed region for psychophysiological interaction analysis (PPI) to identify regions with greater functional connectivity with PAG during volitional vocalization, while the above functionally defined amygdala cluster was used in an ROI PPI analysis. Whole-brain results revealed increased functional connectivity of the PAG with left vLMA during voicing, relative to controlled expiration, while trend-level evidence was observed for increased PAG/amygdala coupling during voicing (p = 0.07, uncorrected). Diffusion tensor imaging (DTI) analysis confirmed structural connectivity between PAG and vLMA. The present study sheds further light on neural mechanisms of volitional vocalization that include multiple inputs from both limbic and motor structures to PAG. Future studies should include investigation of how these neural mechanisms are affected in individuals with voice disorders during volitional vocalization.

BACKGROUND: Whole-brain radiotherapy (WBRT) in patients with brain metastases (BM) is associated with neurocognitive decline. Given its crucial role in learning and memory, efforts to mitigate this toxicity have mostly focused on sparing radiation to the hippocampus. We hypothesized that BM are not evenly distributed across the brain and that several additional areas may be avoided in WBRT based on a low risk of developing BM. METHODS: We contoured 2757 lesions in a large, single-institution database of patients with newly diagnosed BM. BM centroids were mapped onto a standard brain atlas of 55 anatomic subunits and the observed percentage of BM was compared with what would be expected based on that region’s volume. A region of interest (ROI) analysis was performed in a validation cohort of patients from 2 independent institutions using equivalence and one-sample hypothesis tests. RESULTS: The brainstem and bilateral thalami, hippocampi, parahippocampal gyri, amygdala, and temporal poles had a cumulative risk of harboring a BM centroid of 4.83% in the initial cohort. This ROI was tested in 157 patients from the validation cohort and was found to have a 4.1% risk of developing BM, which was statistically equivalent between the 2 groups (P < 1 × 10(–6), upper bound). CONCLUSION: Several critical brain structures are at a low risk of developing BM. A risk-adapted approach to WBRT is worthy of further investigation and may mitigate the toxicities of conventional radiation.

BACKGROUND. Although established guidelines give indications for performing staging brain MRI at initial diagnosis of non-small cell lung cancer (NSCLC), guidelines are lacking for performing surveillance brain MRI for patients without brain metastases at presentation. OBJECTIVE. The purpose of this study is to estimate the cumulative incidence of and risk factors for brain metastasis development in patients with NSCLC without brain metastases at initial presentation. METHODS. This retrospective study included 1495 patients with NSCLC (mean [± SD] age, 65 ± 10 years; 920 men and 575 women) without brain metastases at initial evaluation that included brain MRI. Follow-up brain MRI was ordered at the discretion of the referring physicians. MRI examinations were reviewed in combination with clinical records for brain metastasis development; patients not undergoing MRI were deemed to have not had metastases develop through last clinical follow-up. The cumulative incidence of brain metastases was determined, with death considered a competing risk, and was stratified by clinical stage group, cell type, and epidermal growth factor receptor (EGFR) gene mutation status. Univariable and multivariable Cox proportional hazards regression analyses were performed. RESULTS. A total of 258 of 1495 patients (17.3%) underwent follow-up brain MRI, and 72 (4.8%) had brain metastases develop at a median of 12.3 months after initial diagnosis of NSCLC. Of the 72 patients who had metastases develop, 44.4% had no neurologic symptoms, and 58.3% had stable primary thoracic disease. The cumulative incidence of brain metastases at 6, 12, 18, and 24 months after initial evaluation was 0.6%, 2.1%, 4.2%, and 6.8%, respectively. Cumulative incidence at 6, 12, 18, and 24 months was higher (p < .001) in patients with clinical stage III-IV disease (1.3%, 3.9%, 7.7%, and 10.9%, respectively) than in those with clinical stage I-II disease (0.0%, 0.8%, 1.2%, and 2.6%, respectively), and it was higher (p < .001) in patients with EGFR mutation-positive adenocarcinoma (0.7%, 2.5%, 6.3%, and 12.3%, respectively) than in those with EGFR mutation-negative adenocarcinoma (0.4%, 1.8%, 2.9%, and 4.4%, respectively). Among 1109 patients with adenocarcinoma, independent risk factors for the development of brain metastasis were clinical stage III-IV (hazard ratio [HR], 9.39; p < .001) and EGFR mutation-positive status (HR, 1.78; p = .04). The incidence of brain metastasis over the study interval was 8.7% among patients with clinical stage III-IV disease and 17.4% among those with EGFR mutation-positive adenocarcinoma. CONCLUSION. Clinical stage III-IV and EGFR mutation-positive adenocarcinoma are independent risk factors for brain metastasis development. CLINICAL IMPACT. For patients with clinical stage III-IV disease or EGFR mutation-positive adenocarcinoma, surveillance brain MRI performed 12 months after initial evaluation may be warranted.

Rheumatoid arthritis frequently complicates airway diseases and is associated with high rates of pneumonia and mortality. The relationship between microorganisms colonizing the lower respiratory tract and the subsequent incidence of pneumonia in patients with rheumatoid arthritis is unclear. In this study, we aimed to identify microorganisms colonizing the lower respiratory tract in patients with rheumatoid arthritis related to the risk of developing subsequent pneumonia in these patients.A retrospective cohort study was designed to include a total of 121 patients with rheumatoid arthritis (median age, 67 years; women, 78.5%) who underwent bronchoscopy at three hospitals from January 2008 to December 2017. The following information was extracted from their electronic medical records: patient characteristics, microorganisms detected by bronchoscopy, and subsequent incidences of pneumonia. The patients were divided into groups based on the microorganisms isolated from the lower respiratory tract and compared with control subjects. The cumulative incidence of pneumonia was assessed using the Kaplan–Meier method and log-rank test. Risk factors for pneumonia were analyzed using the Cox proportional-hazards analysis.The most frequently isolated microbes from the lower respiratory tract in descending order were Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. The annual incidence rates of pneumonia per 1000 patients were 100, 62, 132, and 38, in the P. aeruginosa, S. aureus, H. influenzae, and control group, respectively. Patients colonized with P. aeruginosa had a higher frequency of macrolide use and a higher degree of bronchiectasis than patients in the control group. The rate of the subsequent incidence of pneumonia was higher in the P. aeruginosa group (P = 0.038), and P. aeruginosa was an independent risk factor for pneumonia (hazard ratio, 3.504; 95% confidence interval, 1.153–10.330).The colonization of the lower respiratory tract by P. aeruginosa in patients with rheumatoid arthritis was associated with the subsequent incidence of pneumonia.

BackgroundA few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 (COVID-19) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 patients.MethodsBlood samples were collected from 143 COVID-19 patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a second SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured using the enzyme-linked immunosorbent assay to compare false-negative- with positive-result samples.ResultsSensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. IgM-, IgG-, and total-antibody positivity rates in the patients with negative results from the second genetic testing were 22.9%, 47.6%, and 72.4%, respectively. All antibody titers, especially those of the IgG antibody against nucleocapsid protein, were significantly lower in blood samples with false-negative results than in those with positive results.ConclusionsThese findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 patients than required in the guidelines, and situations in which it is useful are limited.Key pointsAnti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 patients is lower than the required clinical sensitivity, although it may be useful in patients at 3–4 weeks after symptom onset but with negative SARS-CoV-2 genetic test results.

Background Existing guidelines are inconsistent regarding the indications for staging brain MRI in patients with newly diagnosed, early-stage non-small cell lung cancer (NSCLC). Purpose To evaluate the diagnostic yield of staging brain MRI in the initial evaluation of lung cancer. Materials and Methods This retrospective, observational, single-institution study included patients with newly diagnosed NSCLC who underwent staging chest CT and staging brain MRI from November 2017 to October 2018. Diagnostic yield was defined as the proportion of patients with brain metastases among all patients. Yield was stratified into clinical stage groups per the eighth edition of the American Joint Committee on Cancer staging guidelines, based on staging chest CT and in adenocarcinoma with epidermal growth factor receptor

The coronavirus disease 2019 (COVID-19) pandemic has forced a re-design of care in radiation oncology. Perhaps more than any other disease site we commonly see, the evaluation and treatment of head and neck cancer has posed the greatest risk of COVID-19 transmission between patients and radiotherapy providers. In our early experience with the novel coronavirus, several staff members were exposed to a COVID-positive patient and this caused us to devise policies and procedures to mitigate further risk in a way that could practically be employed across a large health system while not compromising care delivery. Here, we formulate a concise summary of simple steps, including a novel thermoplastic mask fitting technique and procedures for intraoral immobilization devices, to guide practices and provide new layers of protection for both patients and staff.

Background: Pertuzumab provided overall and progression-free survival (PFS) benefits in HER2-positive metastatic breast cancer patients (pts) in the CLEOPATRA (Clinical evaluation of docetaxel, pertuzumab and trastuzumab) study. However, few studies have described the efficacy of other drugs in combination with pertuzumab plus trastuzumab. Here, we present a pre-specified analysis of eribulin in combination with pertuzumab plus trastuzumab as first- and second-line therapy for advanced or metastatic breast cancer (AMBC) in a multicenter, open-label phase II study (UMIN000012232, JBCRG-M03). Methods: HER2-positive AMBC with no or single prior chemotherapy for AMBC were enrolled. All pts were administered trastuzumab and taxane as adjuvant or first-line chemotherapy. Treatment consisted of eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day cycle and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) plus pertuzumab (840 mg/body loading dose, then 420 mg/ body) once every 3 weeks, all administered intravenously. The primary endpoint was PFS, and secondary endpoints included overall response rate (ORR) and safety. PFS was determined using Kaplan–Meier analysis. Tumor response was assessed according to RECIST ver. 1.1. Results: Fifty pts were enrolled from November 2013 to April 2016. Forty-nine pts were eligible for safety analysis and the full analysis set (FAS) included 46 pts. The median age was 56 years (23–70), and 8 (16%) and 41 (84%) pts were treated in first- and second-line settings, respectively. Eleven pts (23.9%) were de-novo Stage 4, and 35 pts (76.1%) had progressed in metastatic disease after completion of local therapy. Median PFS was 9.3 months (M) (95% confidence interval [CI]: 6.4–12.3). Table 1 shows the efficacy data for each treatment line and includes ORR, complete response rate (CR), partial response rate (PR), stable disease rate (SD), progressive disease rate (PD), not evaluable rate (NE) and PFS in the FAS. The median relative dose intensities of eribulin, trastuzumab, and pertuzumab were 93.3% (77.0%–100%), 100% (96.0%–100%), and 100% (89.7%–100%), respectively, in the FAS. The grade 3/4 adverse events (AE) were neutropenia in 5 pts (10.2%), including 2 pts (4.1%) with febrile neutropenia; hypertension in 3 pts (6.1%), and other AEs in only one patient. The average of the ejection fraction did not decrease significantly. Symptomatic left ventricular systolic dysfunction was not observed. Conclusion: In pts with HER2-positive AMBC, first- and second-line therapy of eribulin in combination with pertuzumab plus trastuzumab demonstrated substantial antitumor activity with an acceptable safety profile. We are planning a phase III study comparing eribulin with taxanes in combination with pertuzumab plus trastuzumab for the treatment of HER2-positive AMBC. Efficacy data for each treatment lineTreatment LineTotal (n=46)First line (n=8)Second line (n=38)PFS (95% CI), months9.3 (6.4-12.3)20.8 (2.8-38.7)8.7 (7.2-10.2)ORR (%)28 (60.9)7 (87.5)21 (55.3)CR (%)8 (17.4)3 (37.5)5 (13.2)PR (%)20 (43.5)4 (50.0)16 (42.1)SD (%)11 (23.9)1 (12.5)10 (26.3)PD (%)5 (10.9)05 (13.2)NE (%)2 (4.3)02 (5.3) Citation Format: Kawaguchi H, Yamashita T, Masuda N, Kitada M, Narui K, Hattori M, Yoshinami T, Matsunami N, Yanagihara K, Kawasoe T, Nagashima T, Bando H, Yano H, Hasegawa Y, Nakamura R, Kashiwaba M, Morita S, Ohno S, Toi M. Phase II study of eribulin in combination with pertuzumab plus trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-07.

Pelvic radiotherapy for gynecologic malignancies traditionally used a 4-field box technique. Later trials have shown the feasibility of using intensity-modulated radiotherapy (IMRT) instead. But vaginal movement between fractions is concerning when using IMRT due to greater conformality of the isodose curves to the target and the resulting possibility of missing the target while the vagina is displaced. In this study, we showed that the use of a rectal balloon during treatment can decrease vaginal displacement, limit rectal dose, and limit acute and late toxicities. Little is known regarding the use of a rectal balloon (RB) in treating patients with IMRT in the posthysterectomy setting. We hypothesize that the use of an RB during treatment can limit rectal dose and acute and long-term toxicities, as well as decrease vaginal cuff displacement between fractions. We performed a retrospective review of patients with gynecological malignancies who received postoperative IMRT with the use of an RB from January 1, 2012 to January 1, 2015. Rectal dose constraint was examined as per Radiation Therapy Oncology Group (RTOG) 1203 and 0418. Daily cone beam computed tomography (CT) was performed, and the average (avg) displacement, avg magnitude, and avg magnitude of vector were calculated. Toxicity was reported according to RTOG acute radiation morbidity scoring criteria. Acute toxicity was defined as less than 90 days from the end of radiation treatment. Late toxicity was defined as at least 90 days after completing radiation. Twenty-eight patients with postoperative IMRT with the use of an RB were examined and 23 treatment plans were reviewed. The avg rectal V40 was 39.3% ± 9.0%. V30 was65.1% ± 10.0%. V50 was 0%. Separate cone beam computed tomography (CBCT) images ( n = 663) were reviewed. The avg displacement was as follows: superior 0.4 + 2.99 mm, left 0.23 ± 4.97 mm, and anterior 0.16 ± 5.18 mm. The avg magnitude of displacement was superior/inferior 2.22 ± 2.04 mm, laterally 3.41 ± 3.62 mm, and anterior/posterior 3.86 ± 3.45 mm. The avg vector magnitude was 6.60 ± 4.14 mm. For acute gastrointestinal (GI) toxicities, 50% experienced grade 1 toxicities and 18% grade 2 GI toxicities. For acute genitourinary (GU) toxicities, 21% had grade 1 and 18% had grade 2 toxicities. For late GU toxicities, 7% had grade 1 and 4% had grade 2 toxicities. RB for gynecological patients receiving IMRT in the postoperative setting can limit V40 rectal dose and vaginal displacement. Although V30 constraints were not met, patients had limited acute and late toxicities. Further studies are needed to validate these findings.

We report the first quasi-optical simulations of wave beams in a hot plasma using the quasi-optical code PARADE (PAraxial RAy DEscription) [K. Yanagihara, I. Y. Dodin, and S. Kubo, Phys. Plasmas 26, 072112 (2019)]. This code is unique in that it accounts for inhomogeneity of the dissipation-rate across the beam and mode conversion simultaneously. We show that the dissipation-rate inhomogeneity shifts beams relative to their trajectories in cold plasma and that the two electromagnetic modes are coupled via this process, an effect that was ignored in the past. We also propose a simplified approach to account for the dissipation-rate inhomogeneity. This approach is computationally inexpensive and simplifies the analysis of actual experiments.

PURPOSE/OBJECTIVE(S) Stereotactic radiosurgery (SRS), compared to whole brain radiotherapy is limited in its ability to prevent development of brain metastases in untreated areas. The purpose of this study is to assess whether low-dose volumes delivered to uninvolved regions of the brain during SRS can reduce the risk of developing brain metastases in those regions. MATERIALS AND METHODS Data were collected for 69 patients with brain metastases who were treated with SRS at least two occasions. The regions of uninvolved brain receiving a high, intermediate, and low dose of incidental radiotherapy were defined as the volume receiving at least 10, 5, and 2.5 Gy if the prescribed dose was < 25 Gy (1-3 fraction plans) or the volume receiving at least 15, 7.5, and 5 Gy if the prescribed dose was ≥ 25 Gy (5 fraction plans). A second round metastasis was considered to occur within a given dose level if 20% or more of the tumor was found within that dose level. Probabilities were calculated based on the volume of each dose level as a percentage of total brain volume and were used to estimate the expected number of cases with at least one metastasis occurring in each dose level. RESULTS The average number of metastases treated in both rounds of SRS was two. The expected and observed number of cases with at least one second round metastasis were 0 and 2 for the high dose level (p=0.151), 7 and 3 for the intermediate dose level (p=0.018), and 17 and 11 for the low dose level (p=0.094). CONCLUSION We observed fewer than expected new metastases within prior SRS low dose levels based on volumetric probabilities, though this difference was only significant for the intermediate dose level. This suggests that low dose volumes from SRS may provide benefit in preventing future regional metastases.

Infection during pregnancy is common and the developing fetal brain is vulnerable to vertical transmission due to immaturity of the fetal immune system. Infection is a major cause of multiple organ abnormalities, including the neuraxis, due to the neurotropism of the infectious agents. This review sets out to give an overview of fetal infection, review the general principles of the nature and timing of the infectious insult with respect to outcomes, review the neuroimaging of infection by ultrasound and magnetic resonance imaging (MRI), and review the various pathogens involved, including the two most common, cytomegalovirus (CMV) and Toxoplasma, and also other common viral and nonviral infections.

Alternating electric fields have been successfully applied to cancer cells in-vitro to disrupt malignant progression and this antimitotic therapy has now been proven to be efficacious in Phase II and Phase III randomized clinical trials of patients with glioblastoma. With additional clinical trials ongoing in a number of other malignancies, there is a crucial need for a better understanding of the radiographic predictors of response and standardization of surveillance imaging interpretation. However, many radiologists have yet to become familiarized with this emerging cancer therapy and there is little active investigation to develop prognostic or predictive imaging biomarkers. This article provides an overview of the pre-clinical data that elucidate the biologic mechanisms of alternating electric fields as a cancer therapy. Results from clinical trials in patients with glioblastoma are then reviewed while elaborating on the several limitations to adoption of this promising line of treatment. Finally, a proposal for the development of imaging markers as a means of overcoming some of these limitations is made, which may improve treatment utilization by augmenting patient selection not only in glioblastoma, but also other malignant conditions for which this therapy is currently being evaluated.

It is common clinical practice to consider the location of a brain metastasis when making decisions regarding local therapies and, in some scenarios, estimating clinical outcomes, such as local disease control and patient survival. However, the location of a brain metastasis is not included in any validated prognostic nomogram and it is unclear if this is due to a lack of a relationship or a lack of support from published data. We performed a comprehensive review of the literature focusing on studies that have investigated a relationship between brain metastasis location and clinical outcomes, including patient survival. The vast majority of reports anatomically categorized brain metastases as supratentorial or infratentorial whereas some reports also considered other subdivisions of the brain, including different lobes or with particular areas defined as eloquent cortex. Results were variable across studies, with some finding a relationship between metastasis location and survival, but the majority finding either no relationship or a weak correlation that was not significant in the context of multivariable analysis. Here, we highlight the key findings and limitations of many studies, including how neurosurgical resection might influence the relative importance of metastasis location and in what ways future analyses may improve anatomical categorization and resection status.

This work continues a series of papers where we propose an algorithm for the quasi-optical modeling of electromagnetic beams with and without mode conversion. The general theory was reported in the first paper of this series, where a parabolic partial differential equation was derived for the field envelope that may contain one or multiple modes with close group velocities. Here, we present a corresponding code paraxial ray description and its test applications to single-mode beams in vacuum and also in inhomogeneous magnetized plasma. The numerical results are compared with analytic formulas from Gaussian-beam optics and also with cold-plasma ray tracing, respectively. The quasi-optical simulations of mode-converting beams are reported in the third paper of this series.This work continues a series of papers where we propose an algorithm for the quasi-optical modeling of electromagnetic beams with and without mode conversion. The general theory was reported in the first paper of this series, where a parabolic partial differential equation was derived for the field envelope that may contain one or multiple modes with close group velocities. Here, we present a corresponding code paraxial ray description and its test applications to single-mode beams in vacuum and also in inhomogeneous magnetized plasma. The numerical results are compared with analytic formulas from Gaussian-beam optics and also with cold-plasma ray tracing, respectively. The quasi-optical simulations of mode-converting beams are reported in the third paper of this series.

This work opens a series of papers where we develop a general quasioptical theory for mode-converting electromagnetic beams in plasma and implement it in a numerical algorithm. Here, the basic theory is introduced. We consider a general quasimonochromatic multi-component wave in a weakly inhomogeneous linear medium with no sources. For any given dispersion operator that governs the wave field, we explicitly calculate the approximate operator that governs the wave envelope $\psi$ to the second order in the geometrical-optics parameter. Then, we further simplify this envelope operator by assuming that the gradient of $\psi$ transverse to the local group velocity is much larger than the corresponding parallel gradient. This leads to a parabolic differential equation for $\psi$ ("quasioptical equation") in the basis of the geometrical-optics polarization vectors. Scalar and mode-converting vector beams are described on the same footing. We also explain how to apply this model to electromagnetic waves in general. In the next papers of this series, we report successful quasioptical modeling of radiofrequency wave beams in magnetized plasma based on this theory., Comment: This is the first part of the three-paper series that also includes arXiv:1903.01357 and arXiv:1903.01364

This work continues a series of papers where we propose an algorithm for quasi-optical modeling of electromagnetic beams with and without mode conversion. The general theory was reported in the first paper of this series, where a parabolic partial differential equation was derived for the field envelope that may contain one or multiple modes with close group velocities. In the second paper, we presented a corresponding code PARADE (PAraxial RAy DEscription) and its test applications to single-mode beams. Here, we report quasi-optical simulations of mode-converting beams for the first time. We also demonstrate that PARADE can model splitting of two-mode beams. The numerical results produced by PARADE show good agreement with those of one-dimensional full-wave simulations and also with conventional ray tracing (to the extent that one-dimensional and ray-tracing simulations are applicable).This work continues a series of papers where we propose an algorithm for quasi-optical modeling of electromagnetic beams with and without mode conversion. The general theory was reported in the first paper of this series, where a parabolic partial differential equation was derived for the field envelope that may contain one or multiple modes with close group velocities. In the second paper, we presented a corresponding code PARADE (PAraxial RAy DEscription) and its test applications to single-mode beams. Here, we report quasi-optical simulations of mode-converting beams for the first time. We also demonstrate that PARADE can model splitting of two-mode beams. The numerical results produced by PARADE show good agreement with those of one-dimensional full-wave simulations and also with conventional ray tracing (to the extent that one-dimensional and ray-tracing simulations are applicable).

The polarization-dependent Hall effect of light was investigated in full-wave simulations for propagation of electron cyclotron waves in magnetized plasma as an anisotropic medium. The transverse shift of the wave packet, which is comparable to the wavelength in the vacuum, was observed in propagation of extraordinary (X) waves under a static magnetic field. This transverse shift is produced by the Berry curvature for the X wave strongly enhanced at the right-hand cutoff. The direction of the transverse shift is perpendicular not only to the gradient of the refractive index but also to the static magnetic field.

Our aim was to develop an automated multiparametric MR imaging analysis of routinely acquired imaging sequences to identify areas of focally recurrent high-grade glioma. Data from 141 patients treated with radiation therapy with a diagnosis of high-grade glioma were reviewed. Strict inclusion/exclusion criteria identified a homogeneous cohort of 12 patients with a nodular recurrence of high-grade glioma that was amenable to focal re-irradiation (cohort 1). T1WI, FLAIR, and DWI data were used to create subtraction maps across time points. Linear regression was performed to identify the pattern of change in these 3 imaging sequences that best correlated with recurrence. The ability of these parameters to guide treatment decisions in individual patients was assessed in a separate cohort of 4 patients who were treated with radiosurgery for recurrent high-grade glioma (cohort 2). A leave-one-out analysis of cohort 1 revealed that automated subtraction maps consistently predicted the radiologist-identified area of recurrence (median area under the receiver operating characteristic curve = 0.91). The regression model was tested in preradiosurgery MRI in cohort 2 and identified 8 recurrent lesions. Six lesions were treated with radiosurgery and were controlled on follow-up imaging, but the remaining 2 lesions were not treated and progressed, consistent with the predictions of the model. Multiparametric subtraction maps can predict areas of nodular progression in patients with previously treated high-grade gliomas. This automated method based on routine imaging sequences is a valuable tool to be prospectively validated in subsequent studies of treatment planning and posttreatment surveillance.

Objective To assess whether early changes in enhancing tumor volume (eTV) and relative cerebral blood volume (rCBV) 1 month after convection-enhanced delivery of topotecan in patients with recurrent malignant glioma correlated with 6-month disease progression status. Methods Sixteen patients were enrolled in a Phase Ib trial of convection-enhanced delivery of topotecan for recurrent malignant glioma. Each patient was evaluated with serial follow-up magnetic resonance imaging at baseline and at 4- to 8-week intervals. Changes at 1 month compared with baseline in eTV and rCBV were evaluated as potential predictors of 6-month progression status, classified as either progressive disease or nonprogressive disease. Relationships between percent changes in eTV and rCBV at 1 month with the probability of progressive disease at 6 months were estimated by the use of logistic regression analysis. Receiver operating characteristic curves for varying percent change thresholds in eTV and rCBV were evaluated by the use of 6-month progressive disease as the reference. Results There was a significant difference in the percent change in rCBV at 1 month in patients with progressive disease compared with those with nonprogressive disease at 6 months (+12% vs. −29%, P = 0.02). Logistic regression analysis demonstrated on average that a 10% increase in rCBV at 1 month after convection-enhanced delivery of topotecan was associated with 1.7 times the odds of developing progressive disease at 6 months (95% confidence interval [CI] 1.0–2.9 P = 0.05). Receiver operating characteristic analysis for determining progressive disease at 6 months showed a greater area under the curve with rCBV (0.867; 95% CI 0.66–1.00) than with change in enhancing tumor volume (0.767; 95% CI 0.51–1.00). Conclusion In this selected population of patients with recurrent malignant glioma treated with convection-enhanced delivery of topotecan, early changes in rCBV at 4 weeks after therapy may help predict progression status at 6 months.

Glioblastoma is the most common adult central nervous system malignancy and carries a poor prognosis. Disease progression and recurrence after chemoradiotherapy are assessed via serial magnetic resonance imaging sequences. T2-weighted fluid-attenuated inversion recovery (FLAIR) signal is presumed to represent edema containing microscopic cancer infiltration. Here we assessed the prognostic impact of computerized volumetry of FLAIR signal in the peri-treatment setting for glioblastoma. We analyzed pre- and posttreatment FLAIR sequences of 40 patients treated at the Columbia University Medical Center between 2011 and 2014, excluding those without high-quality FLAIR imaging within 2 weeks before treatment and 60 to 180 days afterward. We manually contoured regions of FLAIR hyperintensity as per Radiation Therapy Oncology Group guidelines and calculated the volumes of nonenhancing tumor burden. At the time of this study, all but 1 patient had died. Pre- and posttreatment FLAIR volumes were assessed for correlation to overall and progression-free survival. Larger post-treatment FLAIR volumes from sequences taken between 60 and 180 days after conclusion of chemoradiotherapy were negatively correlated with overall survival (P = .048 on Pearson's correlation and P = .017 and P = .043 on univariable and multivariable Cox regression analyses, respectively) and progression-free survival (P = .002 on Pearson's correlation and P = &lt, 001 and P = &lt, 001 on univariable and multivariable Cox regression analyses). This study suggests that higher FLAIR volumes in the 2- to 6-month posttreatment window are associated with worsened survival.

Brain metastases (BMs) are the most common intracranial malignancy and afflict ∼10%–20% of patients with cancer. BMs tend to present at the boundaries of gray and white matter because of the distribution of small vessels. In addition, metastases may not be randomly distributed across gross anatomical regions of the brain, but this has not previously been quantified. We retrospectively analyzed a series of 28 patients with recurrent BMs with a total of 150 lesions. Each lesion was manually defined based on T1 gadolinium-enhanced imaging. Standard brain atlases were used to identify the anatomical brain region affected by each BM and the frequency of metastases in each region was compared with the expected probability, which was assumed to be a random distribution based on the brain volume. After correction for multiple comparisons, the paracingulate gyrus was found to have a statistically significant increase (P = 4.731 × 10−9) in the rate of BMs relative to the random spatial distribution. A nonstochastic spatial distribution of metastases may be used to guide partial brain radiotherapy with risk-adapted dose delivery and reduce the risk of neurotoxicity due to overtreatment.

Background Monocytes can differentiate into either proinflammatory, microbicidal M1 macrophage or anti-inflammatory M2 macrophage subtypes. In addition to macrophages, regarding monocyte subsets, M1 monocytes and M2 monocytes mirroring the M1/M2 macrophage polarization concept were suggested. Little is known regarding the relationships between osteoclastogenesis and M1/M2 monocyte subsets. Objectives We investigated the relationships among M1 monocytes, M2 monocytes, osteoclast differentiation ability and clinical characteristics in patients with rheumatoid arthritis (RA). Methods Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We defined positive CD14, CD68 and CCR2 monocytes as M1 monocytes, and in separate tubes, we defined positive CD14, CX3CR1 and CD163 or CD206 monocytes as M2 monocytes. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate osteoclast differentiation in vitro. We defined osteoclasts as tartrate-resistant acid phosphatase (TRAP) staining-positive cells with >3 nuclei. We counted the osteoclasts in the whole wells of a 96-well dish. Pit formation assays were performed to evaluate function of osteoclasts. Results Forty RA patients and 20 healthy donors were included. Twenty-two patients (55%) were ACPA-positive. The median M1/M2 ratio was 0.59 (0.31–1.11, IQR). There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated osteoclast number in vitro in RA patients (ρ=0.81, p The ACPA-positive patients had significantly higher M1/M2 ratio in vivo (p=0.028) (E) and significantly greater numbers of osteoclasts in vitro (p Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis (β-coefficient 16.3, p RA patients with M1/M2 ratio >1 (having relatively more M1 monocytes) had higher erythrocyte sedimentation rates (p=0.011) and C-reactive protein (p=0.032) than RA patients with M1/M2 ratio ≤1. M1-dominant monocytes in vitro produced higher concentrations of IL-6 upon stimulation with lipopolysaccharide than M2 monocytes (p=0.032). Conclusions The M1/M2 ratio is strongly correlated with the in vitro differentiation of osteoclasts in patients with RA. The RA patients with positive ACPA had higher M1/M2 ratio and higher numbers of osteoclasts. M1 and M2 monocyte subsets may become a new target of treatments for RA. Disclosure of Interest None declared