This study aims to develop a model designed to effectively respond to fluctuations in energy demand. It involves constructing a physics-based simulation capable of real-time performance prediction for a two-stage centrifugal pump system. The model is composed of Modelica and a Reduced-order Model(ROM). It predicts key performance indicators such as pump head and flow rate in real-time. Additionally, a multi-parameter calibration framework using Bayesian optimization was applied to reflect the actual performance of the pump. This framework calibrates the parameters of the Modelica model. As a result, the error rates for flow rate and head were reduced to 2.87% and 3.58%, respectively.

Circ Cardiovasc Interv. 2023;16:e012621. DOI: 10.1161/CIRCINTERVENTIONS.122.012621 March 2023 Correspondence to: Joo Myung Lee, MD, MPH, PhD, Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea. Email drone80@hanmail.net *D. Hong and D. Shin contributed equally. Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCINTERVENTIONS.122.012621. For Sources of Funding and Disclosures, see page 109. © 2023 American Heart Association, Inc. ORIGINAL ARTICLE

Periodic leg movements during sleep (PLMS) are repetitive and involuntary jerking movements of the legs during sleep. PLMS are observed in many patients with sleep disorders including restless legs syndrome (RLS). Decreased dopamine transmission associated with neuronal hyper-excitability of the central pattern generator has been suggested as the pathophysiology of PLMS. However, its localization and the origin of rhythmicity remains uncertain. Here, we investigated the intracerebral sources of PLMS using electroencephalographic (EEG) spectral power analysis, and for the first time showed the correlation between rhythmicity of PLMS and intracerebral source. Polysomnography data of 14 patients with RLS were included in the present study. Electromyographic, 19-channel EEG with 10–20 system, and electrocardiographic (ECG) signals were obtained. To investigate PLMS-related neural synchronies, delta-band (2–4 Hz) and alpha-band (8–12 Hz) activities were analyzed. Spectral power for EEG channels was obtained and topography or average values were measured. The data were analyzed compared to the values of baseline interval which was set to -15 to -10 seconds preceding to the leg movement (LM) onset. Source localization was done using the head model in FreeSurfer toolbox and Beamformer method to solve inverse problems. Correlation between PLMS rhythmicity (PLMS index or inter-movement interval (IMI)) and intracerebral sources were tested. EEG and ECG signals began to change at 3–4 second ahead of LM onset. Especially, delta-band was the first signal to increase, and was immediately followed by ECG and alpha-band signals. Before the LM onset, the source of delta-band was localized into right precentral gyrus between -3 and -2 second. Just after LM onset, the source was at bilateral superior frontal gyri. During -5 and -2 seconds, PLMS index was correlated with delta power in left anterior cingulate gyrus, and IMI was negatively correlated with both left anterior cingulate gyrus and right inferior parietal gyrus. Intracerebral sources of PLMS differed temporally according to the EEG signals. Rhythmicity of PLMS was well correlated with electrophysiological spectral power in cingulate gyrus. Our data provide insight into a cortical organizing mechanism of PLMS. None.

Restless legs syndrome (RLS) is a sensorimotor neurological disorder that is frequently accompanied by sleep disturbances. The neurophysiological mechanisms of spindle generation reflect interactions between inhibitory cells in the thalamic reticular nucleus (RE) and bursting thalamocortical (TC) relay neurons. Sleep spindles have been implicated in multiple brain functions, including sleep quality, sensory gating, learning, and memory. As increased thalamic glutamatergic activities in RLS has been reported, which may be related to the arousal disrupting sleep, we hypothesized that patients with RLS may have abnormal sleep spindles activities during sleep. Fifteen drug-naïve idiopathic RLS patients and 15 healthy controls were participated in this study. Nineteen channel electroencephalograms (EEGs) were recorded during the sleep. Automated sleep spindle detection algorithm was used for extracting slow (9–12 Hz) and fast (12–15 Hz) sleep spindle event. Quantitative characteristics of sleep spindle activity were obtained by analyzing EEG power spectra. For both slow and fast sleep spindle activity, decreased spindle density was observed in RLS group compared with control group. Oscillatory power of fast and slow sleep spindles was significantly reduced in RLS group. Fast sleep spindle density in RLS group negatively correlated with wake time after sleep onset (WASO) (r=-0.548, p=0.034). Fast sleep spindle power in control group was positively correlated with portion of slow wave sleep (%) (r=0.5956, p=0.0192). However, no significant correlation was found in RLS group (r=0.0237, p=0.9331). Abnormal sleep spindle activity in RLS support the notion of underlying impaired cortical thalamic communication in RLS, which might contribute to disturbance in sleep integrity. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2017R1A2B2012280) and the Brain Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning (2017M3C7A1029485).

Periodic leg movements in sleep (PLMS) are present in more than 80% of patients with restless legs syndrome (RLS). Some leg movements in sleep (LM) do not satisfy the PLMS diagnostic criteria, which are called non-periodic leg movement (NPLM). They can be classified as short-interval LM in sleep (SILMS, IMI<10s), isolated LM in sleep (ILMS, IMI>90s), and others. PLMS are associated with arousals and autonomic activation, which may contribute to higher cardiovascular disease risk in patients with RLS. Thus, the aim of this study is to evaluate clinical impacts of SILMS and ILMS in patients with RLS by comparison of heart rate related SILM, ILMS between patients and controls. In this retrospective case-control study, 10 idiopathic RLS patients and 10 controls were included. LMs were automatically detected within polysomnography (PSG). Objective sleep quality was measured with PSG findings including total sleep time, sleep latency and slow wave sleep. Subjective sleep quality was measured with Pittsburgh Sleep Quality Index (PSQI). RLS severity was measured with International Restless Legs Syndrome Study Group Rating Scale (IRLS). We assessed the correlation between frequencies of SILMS, ILMS, PLMS and RLS severity, sleep quality. In addition, correlation between heart rate associated each LM type and clinical factors was evaluated. Frequencies of SILMS, ILMS and PLMS in patients with RLS were not significantly different compared to controls. However, patients presented higher heart rate associated with SILMS (p=0.011) and ILMS (p=0.026) than controls, but not heart rate associated with PLMS. Heart rate related to SILMS and ILMS were correlated with IRLS scale (r=0.7262, p=0.0188 and r=0.7632, p=0.0147, respectively) and PSQI (r=0.724, p=0.0178 and r=0.6420, p=0.0454, respectively) in patients with RLS. Heart rate associated with PLMS did not show correlation with IRLS scale in patients. Our results suggest that cardiac activation related to SILMS and ILMS might contribute to sleep disturbance and sensorimotor symptom in patients with RLS. none.

According to Korean’s National Nutrition Examination Surveys, hypertension patients’ awareness, treatment, and control rate are low despite high prevalence. This study aims to investigate medication adherence and quality of life (QoL) of uncontrolled hypertension patients in Korea. Inclusion criteria are as follows; over 20 yrs old, patients whose systolic blood pressure (SBP) > 140mmHg or diastolic blood pressure (DBP) > 90mmHg, despite taking antihypertensive drugs Demographic characteristics, treatment status (controlled / uncontrolled) and patient reported outcome (EQ-5D, Morisky 4-Items Self-Report Measure of Medication questionnaire (MMAS-4)) were assessed at baseline, 3 months (FU1), and 6 months (FU2) after enrollment. We enrolled 1,001 patients from 13 university hospitals and collected data prospectively in the period from February, 2014 to June, 2016. Mean age of patients was 64.6±12.5 years old and male was 52.3%. The mean SBP decreased from 150.8mmHg at baseline to 134.3 at FU2, and the mean DBP from 85.7 to 79.2mmHg; 59% of patients had controlled hypertension during follow up. The patients’ QoL was analyzed by the EQ-5D and the mean score was 0.87±0.11, 0.88±0.11 and 0.87±0.11 at baseline, FU1 and FU2 respectively. Medication adherence was analyzed by MMAS-4, the mean score was 0.52±0.82 and 0.45±0.75 (lower score means better adherence) at FU1 and FU2 respectively. For items of MMAS-4 at FU2, patients who responded question that ask ever forgetting or feeling tired to take drugs was 22.8%, 18.8% respectively; only 67.9% patients are fully adherent. Patient with better medication adherence show higher rate of controlled hypertension and higher QoL analyzed by EQ-5D. The patient group whose BP was well controlled showed higher EQ-5D-VAS score. Our data demonstrates there are still rooms for improvement of medication adherence. Since medication adherence, blood pressure control and quality of life are closely inter-related, strategy to enhance medication adherence would be clinically important.

There are increasing role of ECMO in refractory cardiogenic shock. Among them, temporary support for myocardial stunning during peri-myocardial infarction period is utmost importance. However, there are mostly small case series of single center experiences. We aimed to evaluate the role and characteristics of open use of ECMO from tertiary centers at current highly developed medical and procedural era. Of 11,974 patients of acute myocardial infarction from March 2006 through December 2014, 1,022 patients (8.5%) were complicated with cardiogenic shock during index hospitalization. Patients with available data were divided into two groups according to application of ECMO. Of 766 patients, 115 (15%) patients were in ECMO group and 651 (85%) patients were in No-ECMO group. Primary outcome was the in-hospital mortality. Survival analysis after propensity matching was performed. Patients in ECMO group were younger, and had low initial mean blood pressure, large infarct size, and more left-sided coronary disease as target vessel. Cardiogenic shock developed in ECMO group at mean 1.2 days, and 1.4 days in No-ECMO group without statistically significant difference. ECMO application was performed at 0.4 days from cardiogenic shock. Crude in-hospital mortality rate was significantly higher in ECMO group (81.7% vs. 35.5%, p<0.0001) compared to the NO-ECMO group. However, there was no statistical difference after propensity score matching in in-hospital mortality (76% in ECMO group vs. 52% in No-ECMO group, p=0.08). ECMO was not a significant predictor for in-hospital mortality after matching (OR 1.505, 95% CI 0.907-2.498, p=0.11). Within ECMO subgroup, early insertion of ECMO within admission day, co-treatment with IABP, and no CPR were associated with in-hospital survival. Among acute myocardial infarction patients complicated with cardiogenic shock, open use of ECMO was not associated with increased in-hospital mortality. Timely approach of ECMO might augment its beneficial effect.

Objective: Fimasartan is a new antihypertensive drug which blocks AT-1 receptor selectively. It exhibited a potent antihypertensive effect and quick onset of the effect. We investigated antihypertensive effect of 60 and 120 mg of Fimasartan and its safety in comparison with 8 mg of Candesartan. Design and method: After 2 weeks’ placebo run-in period, 290 patients with mild to moderate hypertension (diastolic blood pressure (DBP), 90 ∼ 110 mmHg) aged from 19 to 75 years old were randomly assigned to 60 mg, 120 mg daily of Fimasartan or 8 mg daily of Candesartan. They were administered for 12 weeks without dosage adjustment. Primary endpoint was difference in changes of DBP from baseline at 12 weeks. Results: After 12 weeks’ treatment, DBP and systolic blood pressure (SBP) were decreased significantly in all 3 groups. The decrease of DBP at 12 weeks was larger, but not statistically significant, in Fimasartan 60 mg compared with the Candesartan 8 mg group with the difference of 1.72 ± 8.32 mmHg (95% confidence interval, -0.71∼ 4.15 mmHg, p = 0.16). Lower margin of the confidence interval, -0.71 mmHg, exceeded the pre-defined non-inferiority margin, -3.0 mmHg. DBP lowering effect of Fimasartan 120 mg was also non-significantly larger than the candesartan 8 mg (difference, 1.58 ± 8.27 mmHg, p = 0.20). The decrease of SBP was also non-significantly larger in Fimasartan 60 mg compared with the candesartan 8 mg group (difference, 3.50 ± 12.63 mmHg, p = 0.06). However, SBP lowering effect of the Fimasartan 120 mg was statistically larger than the candesartan 8 mg (difference 4.98 ± 13.99 mmHg, p = 0.02). Responder rate (DBP < 90 mmHg or DBP lowering > 10 mmHg at 12 weeks) was also non-significantly greater in both Fimasartan groups (Fimsartan 60 mg, 81%; Fimasartan 120 mg, 72%; Candesartan 8 mg, 71%). Safety profile of the Fimasartan 60 mg and 120 mg was similar to candesartan 8 mg, with slightly higher, but statistically not significant, incidence of hepatic enzyme elevation in Fimasartan 120 mg. Conclusions: Fimasartan, a newly available AT-1 receptor blocker, is an effective antihypertensive agent, comparable to candesartan, with good safety profile.

Sir, Monoclonal gammopathies are a group of disorders characterized by the production of monoclonal immunoglobulins (M-proteins) by clonal plasma cells. The standard methods for identification of M-proteins include serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE) and quantitative serum free light chain (sFLC) assay. Also, capillary zone electrophoresis (CZE) and immunosubtraction-capillary electrophoresis (IS-CE) have been used increasingly in clinical laboratories as alternatives for the conventional agarose gel electrophoresis and IFE because of slightly higher sensitivity and technical feasibility. Recently, an automated immunoassay that provides quantitative measurement of specific pairs of heavy/light chains (HLCs) and also the HLC ratio (Ig′j/Ig′k) for each class of immunoglobulin (Ig) has been introduced [1]. This new HLC measurement can identify the absolute value of the involved IgGj, IgGk, IgAj, IgAk, IgMj, and IgMk separately, along with their ratios. Hence, we evaluated the performance of the HLC assay in diagnosing and monitoring patients with intact immunoglobulin multiple myeloma (IIMM) and compared the use of HLC assay with the routine serologic tests. This study was approved by the Institutional Review Board at Catholic Medical Center (KC11EISI0646). HLC assay was conducted using Hevylite turbidimetric immunoassay (The Binding Site, Birmingham, UK) on SPAPLUS analyzer (The Binding Site). HLC ratio was calculated with the involved intact Ig as the numerator and the polyclonal intact Ig of the same class as the denominator. Statistical analyses were performed using the MedCalc version 12.1.4 (MedCalc Software, Mariakerke, Belgium). The 95% reference intervals were verified using sera from 30 Korean healthy individuals (16 men and 14 women, mean age SD of 51.5 10.0 years) (IgGj 3.84–12.07, IgGk 1.91–6.74, IgGj/IgGk 1.12–3.21, IgAj 0.57–2.08, IgAk 0.44–2.04, IgAj/IgAk 0.78–1.94, IgMj 0.19–1.63, IgMk 0.12–1.01, IgMj/IgMk 1.18–2.74). An abnormal HLC ratio was defined as any value outside the 95% reference interval. The correlation of the summed concentrations of lightchain pairs of each Ig class, measured by HLC, with the respective total IgG, IgA, and IgM was as follows; coefficient of correlation (R) = 0.835, 0.941, and 0.961, respectively. Serum samples of 109 IIMM patients were retrospectively analyzed (49 men and 60 women, median age of 62 (37–81)). Paraprotein types were IgG in 65 patients (46 IgGj, 19 IgGk), IgA in 35 (20 IgAj, 15 IgAk), and IgM in 9 (8 IgMj, 1 IgMk). The routine serologic tests performed in this lab consisted of total protein: IgG, IgA, IgM, CZE, IS-CE, and sFLC assays. The diagnostic performance of the HLC assay at initial presentation of IIMM showed full agreement in the clonality assessment and M-protein characterization. Thirteen patients (7 IgG, 4 IgA, 2 IgM), who initially presented with IIMM, had abnormal HLC concentrations and HLC ratios. The monoclonal typing obtained with the HLC assay agreed with the CZE and IS-CE results in all patients. sFLC assay did not detect one initial IgMj IIMM patient. In 98 (89.9%) of the 109 samples, the isotope-specific HLC ratios accurately predicted the presence or absence of M-protein even in those cases associated with a low concentration of M-protein. The sensitivity of HLC ratio was 91.0% and specificity 77.4% compared with CZE and IS-CE. Eleven samples gave discrepant results, and 7 of them showed normal HLC ratios with detectable M-protein by CZE and IS-CE, and 4 showed abnormal HLC ratios without an M-protein (Table 1). Of the 7 samples, with false-negative HLC ratios, 4 had M-protein concentrations near the detection limit of quantitation of CZE and IS-CE (0.020 g/dL). Of the 4 samples with false-positive HLC ratios, 3 of them had normal or near-normal HLC concentrations despite of abnormal HLC ratios. In one case (case 11), both HLC concentration and HLC ratio were abnormal, but M-protein was not detected by CZE and IS-CE. Subsequent follow-up revealed a relapse in 2 months time after the HLC measurements were made (Figure 1). International guidelines recommend the use of SPEP or CZE to screen for the presence of M-protein, and the

Study ObjectivesThe aim of this study is to evaluate prevalence of 6H5T, suggested by American Heart Association (AHA) for considering causes of cardiac arrest and to compare to that of cerebral hemorrhage and aortic dissection.MethodsWe enrolled non-traumatic out-of-hospital cardiac arrest patients who visited ED from 12th November, 1996 to 6th June, 2008 and reviewed their medical records on CAD-WCHED (Cardiac Arrest Database-Wonju Christian Hospital Emergency Department).ResultsThe number of cases enrolled during study period was 1798. Among 1798 cases, the number of non-traumatic out-of-hospital cardiac arrest patients who had PEA or asystole on ED arrival was 1159 (64.4%). Male were 63.7% (738 cases) and mean ages were 55±19 years old in male, 63±18 years old in female. When we classify causes of non-traumatic out-of-hospital cardiac arrest as to 6H5T, 68 cases (5.9%) were hypovolemia, 210 cases (18.1%) were hypoxia, 41 cases (3.5%) were hydrogen ion, 38 cases (3.3%) were hypo/hyperkalemia, 1 case (0.1%) was hypoglycemia, 5 cases (0.4%) were hypothermia, 50 cases (4.3%) were toxin, 10 cases (0.9%) were tamponade (cardiac), 6 cases (0.5%) were tension pneumothorax, 291 cases (25.1%) were thrombosis, and the causes of 353 cases (30.5%) were unknown. Aortic dissection had 25 cases (2.2%) and spontaneous cerebral hemorrhage had 40 cases (3.5%).ConclusionThe prevalence of cerebral hemorrhage and aortic dissection were similar to that of hydrogen ion, hypo/hyperkalemia, toxin and higher than that of hypoglycemia, hypothermia, tamponade (cardiac), and tension pneumothorax. So we suggest to add 1H1T (“Hemorrhage of cerebrum” and “Tear of the aorta”) to 6H5T for evaluation of causes of non-traumatic out-of-hospital cardiac arrest. Study ObjectivesThe aim of this study is to evaluate prevalence of 6H5T, suggested by American Heart Association (AHA) for considering causes of cardiac arrest and to compare to that of cerebral hemorrhage and aortic dissection. The aim of this study is to evaluate prevalence of 6H5T, suggested by American Heart Association (AHA) for considering causes of cardiac arrest and to compare to that of cerebral hemorrhage and aortic dissection. MethodsWe enrolled non-traumatic out-of-hospital cardiac arrest patients who visited ED from 12th November, 1996 to 6th June, 2008 and reviewed their medical records on CAD-WCHED (Cardiac Arrest Database-Wonju Christian Hospital Emergency Department). We enrolled non-traumatic out-of-hospital cardiac arrest patients who visited ED from 12th November, 1996 to 6th June, 2008 and reviewed their medical records on CAD-WCHED (Cardiac Arrest Database-Wonju Christian Hospital Emergency Department). ResultsThe number of cases enrolled during study period was 1798. Among 1798 cases, the number of non-traumatic out-of-hospital cardiac arrest patients who had PEA or asystole on ED arrival was 1159 (64.4%). Male were 63.7% (738 cases) and mean ages were 55±19 years old in male, 63±18 years old in female. When we classify causes of non-traumatic out-of-hospital cardiac arrest as to 6H5T, 68 cases (5.9%) were hypovolemia, 210 cases (18.1%) were hypoxia, 41 cases (3.5%) were hydrogen ion, 38 cases (3.3%) were hypo/hyperkalemia, 1 case (0.1%) was hypoglycemia, 5 cases (0.4%) were hypothermia, 50 cases (4.3%) were toxin, 10 cases (0.9%) were tamponade (cardiac), 6 cases (0.5%) were tension pneumothorax, 291 cases (25.1%) were thrombosis, and the causes of 353 cases (30.5%) were unknown. Aortic dissection had 25 cases (2.2%) and spontaneous cerebral hemorrhage had 40 cases (3.5%). The number of cases enrolled during study period was 1798. Among 1798 cases, the number of non-traumatic out-of-hospital cardiac arrest patients who had PEA or asystole on ED arrival was 1159 (64.4%). Male were 63.7% (738 cases) and mean ages were 55±19 years old in male, 63±18 years old in female. When we classify causes of non-traumatic out-of-hospital cardiac arrest as to 6H5T, 68 cases (5.9%) were hypovolemia, 210 cases (18.1%) were hypoxia, 41 cases (3.5%) were hydrogen ion, 38 cases (3.3%) were hypo/hyperkalemia, 1 case (0.1%) was hypoglycemia, 5 cases (0.4%) were hypothermia, 50 cases (4.3%) were toxin, 10 cases (0.9%) were tamponade (cardiac), 6 cases (0.5%) were tension pneumothorax, 291 cases (25.1%) were thrombosis, and the causes of 353 cases (30.5%) were unknown. Aortic dissection had 25 cases (2.2%) and spontaneous cerebral hemorrhage had 40 cases (3.5%). ConclusionThe prevalence of cerebral hemorrhage and aortic dissection were similar to that of hydrogen ion, hypo/hyperkalemia, toxin and higher than that of hypoglycemia, hypothermia, tamponade (cardiac), and tension pneumothorax. So we suggest to add 1H1T (“Hemorrhage of cerebrum” and “Tear of the aorta”) to 6H5T for evaluation of causes of non-traumatic out-of-hospital cardiac arrest. The prevalence of cerebral hemorrhage and aortic dissection were similar to that of hydrogen ion, hypo/hyperkalemia, toxin and higher than that of hypoglycemia, hypothermia, tamponade (cardiac), and tension pneumothorax. So we suggest to add 1H1T (“Hemorrhage of cerebrum” and “Tear of the aorta”) to 6H5T for evaluation of causes of non-traumatic out-of-hospital cardiac arrest.

Purpose: We present a multiple-objective treatment planning framework that involves a wide range of treatment planning variables and multiple clinical objectives and constraints. Our goal is to compare the quality of resulting treatment plans from a multiple-objective approach versus plans from current clinical systems. The techniques is applied across two clinical sites (thus with different clinician preferences and outcome endpoints) to observe consistency of the proposed methods. Methods and Materials:We combine preemptive programming and weighted sum approaches within a large-scale discrete optimization framework to manage the multiple clinical objectives. Four objectives are optimized explicitly: PTV homogeneity, conformity, OAR doses and OAR DVHs. Elements of uncertainty in constraints (e.g., best possible limiting dose bounds to OARs) are preemptively determined and adaptively incorporated into the treatment planning model. Results:Compared to clinical plans, for a collection of 10 head-and-neck cases from 2 clinics, PTV homogeneity improves by 5–14% when using the multiple objective approach, whereas conformity improves by 2–5%. The mean-dose to organs-at-risks reduces uniformly by 8–42% for parotid, 6–30% for mandible, 10–28% for larynx, and 7–22% for oral cavity. In particular, all critical structures receive significantly less dose, as the multiple objective approach focuses the radiation onto the tumor volume. The plans provide over 95% PTV coverage, as requested by the clinicians. Conclusion:The multiple-objective approach produces very high-quality plans. Although the resulting solution is sensitive with respect to the order the objectives are optimized and prioritized, across the two clinical sties, the multiple objective schema works consistently well. Specifically, at both sites, the multiple objective approach results in plans with drastic dose reduction to critical structures, while simultaneously improving PTV coverage, conformity, and dose homogeneity when compared to plans obtained via commercial planning systems. Elements of uncertainty in constraints can be preemptively determined. Computationally it takes about an hour to generate each plan.

Purpose: Although surgery remains the treatment of choice, patients with carcinoma of the extrahepatic bile duct who are not candidates for surgical resection(∼75%) are treated palliatively with radiation therapy and/or chemotherapy. Intraluminal LDR or HDR brachytherapy has the well‐documented advantage of delivering a large target dose, while significantly sparing surrounding healthy tissues. Typically, treatment planning is performed with respect to source‐guide catheter(s) inserted along the biliary canal under fluoroscopic guidance. The prescription hull refers to a volume at a distance of 0.5–1.0 cm from catheter(s). Because of the irregular shape of the source guides, manual contouring of the prescription hull is time consuming and subject to errors. We describe, and illustrate with actual treatment plans, an automatic algorithm to outline the planning volume. Methods and Materials: The contouring of a single catheter can be considered as the trajectory generated by a moving ball. The path of the ball forms a guide curve, which is given by the digitized‐coordinates of the source‐guide catheter. Given a radius r that defines the thickness of the PTV, our volume‐definition algorithm applies curve fitting via Ferguson spline interpolation, followed by circle generation and sphere generation. For multiple catheters, the algorithm is more complex, requiring curve fitting, warping, slicing, and linking to obtain the resulting tumor shape. Results: For the biliary intraluminal case, the algorithm takes only seconds to generate a 3D‐planning volume. Applying it to complex hypothetical cases reveals that it handles irregular tumor volumes and shapes well, and returns a 3D‐planning volume within 1 CPU‐minute. Conclusion: The automatic volume‐definition algorithm works reliably and quickly, and results in plans that are demonstratively superior to those obtained by manual planning. Furthermore, the planning volume is a necessary input to computer‐based plan optimization. The volume‐definition algorithm improves the treatment dosimetric conformity, a factor that may contribute to improved clinical outcome.

We present an adaptive IMRT treatment planning approach that is guided by 3D/4D images and that allows exploration of a wide range of beam angles for optimal treatment design. Computational advances to improve solution times are highlight, and robustness of the method and quality of the resulting plans are compared.We focus on column generation of adaptable and clinically acceptable plans. Binary (0/1)variables are used to capture “on”/“off” for each beam. Guided by the tumor image, these candidate beams are generated dynamically throughout the solution process. The treatment model includes explicit clinical constraints, including constraints based on upper/lower/mean dose, approximate organs‐at‐risks dose‐volume relationships, and PTV homogeneity and coverage. During the solution process, at most k active beams are allowed in the branch‐and‐price framework(where k is input by clinicians and is patient/tumor‐specific).Compared to clinical plans, for prostate cases, PTV homogeneity improves by 8–11%, whereas mean‐dose to rectum and bladder reduce uniformly by over 50%. For head‐and‐neck cases, left‐parotid mean dose reduces uniformly by over 50%. In particular, all critical structures receive significantly less dose, as the adaptive approach focuses the radiation onto the tumor volume. The adaptive plans provide over 95% PTV coverage, as requested by the clinicians.The adaptive branch‐and‐price approach proves efficient to simultaneously optimize the beam orientations over the entire space of gantry angles and the fluence map. Two significant advances were made: 1) We efficiently and rapidly solved previously intractable large‐scale treatment instances with important clinical constraints to optimality. 2)We designed a rapid column‐generation approach where candidate beams are chosen adaptively and dynamically, and where the set of active beams are set to clinically acceptable values. These properties allow for generation of plans that are practical for actual delivery and guided in real‐time by tumor images. Clinical experiments showed that our approach produces superior plans.

We sought to determine the risk factors for mortality in organophosphate poisoning.

Uncertainties in the precise locations of tumor voxels are inherent for a variety of reasons. It is therefore desirable to take those uncertainties into account, and further, to derive treatment planning methodologies that directly utilize information (e.g. probability distributions or actual trajectories) about the location of the target, including spatial uncertainties, so that resulting treatment plans exhibit normal tissue dose reduction, and potentially higher tumor doses.Two novel robust approaches are investigated. 1)Under‐dose probability(UDP) estimates the probability of the tumor receiving a dose less than a user‐defined critical dose. It can be modeled using linear mixed‐integer programming techniques. 2)Probability dose generation(PDG) designs treatment plans in which the probability of a voxel located in a target is factored during the dose generation process. Utilizing 4D‐CT scans of lung/liver cancer patients during different breathing phases(phases 0–9, 0:full‐inhale, 5:full‐exhale), four treatment planning strategies are compared. 1)Standard planning with a static PTV based on a single selected phase (control). 2)The Internal Target Volume (ITV) approach, where ITV is defined as the union of CTVs in all breathing phases. 3)Plans obtained with UDP. 4)Plans obtained via PDG. Sophisticated computational optimization techniques are used to solve each of these models.Compared to Standard and ITV plans, UDP and PDG plans offer good coverage, comparable min‐PTV‐dose, improved PTV‐conformity, and higher PTV‐dose. In addition, in lung, PDG reduces normal‐lung‐mean‐dose by 13% and heart‐mean‐dose by 20%; and UDP reduces esophagus‐mean‐dose by 70% and heart‐mean‐dose by 49%. In liver, PDG reduces normal‐liver‐ mean‐dose by 8% and other‐normal‐tissue‐mean‐dose by 26%, whereas UDP reduces normal‐liver‐mean‐dose by 10%, both with improved PTV‐conformity of 7%.Thus, the UDP and PDG approaches can result in treatment plans of increased robustness, they allow a reduction in mean dose to organs‐at‐risk and normal tissue, and in some cases, deliver higher dose to the tumor volume.