Simultaneous integrated boost with intensity modulated radiation therapy in brain oligometastases: A feasible technique for developing countries

PubMed Central

Tiwari, Vivek; Pande, Subodh C.; Verma, Kamal; Goel, Sandeep

2015-01-01

Introduction: To analyze the pattern of brain metastasis (BM), and to use intensity modulated radiation therapy (IMRT) for target dose escalation in cases with ≤3 metastatic lesions (oligometastases). Materials and Methods: Thirty-two consecutive cases of BM treated during September 2009 to August 2012 were analyzed retrospectively. Results: The study comprised 13 males (40.62%) and 19 females (59.37%). Thirteen (40%) patients presented with disseminated intracranial metastases, while 19 (60%) had ≤3 foci. In 25 cases (78%), the primary was located either in the breast (14 cases) or lung (11 cases). The 13 patients with disseminated intracranial metastases received whole brain radiation therapy to a dose of 30 Gy/10-12 daily fractions (Group A) while the 19 cases with ≤3 lesions received an additional dose of 6-10 Gy to gross lesions using a simultaneous integrated boost (SIB) with IMRT thus receiving a total dose of 36-40 Gy/12-15 fractions (Group B). Overall survival (OS) for the breast primary was 6.3 and lung primary was 5.3 months, respectively. The mean OS for breast cases in Group B was higher (9.5 months) as compared to Group A cases (1.9 months) and was statistically significant (P = 0.0056). Similarly, primary lung cancer cases in Group B showed a mean OS of 8.75 months versus 2.6 months for Group A cases (P = 0.213). Conclusions: IMRT is a safe and effective technique in cases with oligometastases for dose escalation in the form of SIB. PMID:25839012

Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial.

PubMed

But-Hadzic, Jasna; Anderluh, Franc; Brecelj, Erik; Edhemovic, Ibrahim; Secerov-Ermenc, Ajra; Hudej, Rihard; Jeromen, Ana; Kozelj, Miran; Krebs, Bojan; Oblak, Irena; Omejc, Mirko; Vogrin, Andrej; Velenik, Vaneja

2016-12-01

This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m 2 /12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Intensive Care, Intense Conflict: A Balanced Approach.

PubMed

Paquette, Erin Talati; Kolaitis, Irini N

2015-01-01

Caring for a child in a pediatric intensive care unit is emotionally and physically challenging and often leads to conflict. Skilled mediators may not always be available to aid in conflict resolution. Careproviders at all levels of training are responsible for managing difficult conversations with families and can often prevent escalation of conflict. Bioethics mediators have acknowledged the important contribution of mediation training in improving clinicians' skills in conflict management. Familiarizing careproviders with basic mediation techniques is an important step towards preventing escalation of conflict. While training in effective communication is crucial, a sense of fairness and justice that may only come with the introduction of a skilled, neutral third party is equally important. For intense conflict, we advocate for early recognition, comfort, and preparedness through training of clinicians in de-escalation and optimal communication, along with the use of more formally trained third-party mediators, as required. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

Intensity-modulated proton therapy further reduces normal tissue exposure during definitive therapy for locally advanced distal esophageal tumors: a dosimetric study.

PubMed

Welsh, James; Gomez, Daniel; Palmer, Matthew B; Riley, Beverly A; Mayankkumar, Amin V; Komaki, Ritsuko; Dong, Lei; Zhu, X Ronald; Likhacheva, Anna; Liao, Zhongxing; Hofstetter, Wayne L; Ajani, Jaffer A; Cox, James D

2011-12-01

We have previously found that ≤ 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p<.0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p≤.0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p<.001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p≤.02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p<.0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p≤.005), heart (p≤.003), and liver (p≤.04). Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigated further in a prospective trial at our institution. Copyright © 2011 Elsevier Inc. All rights reserved.

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu; Schipper, Mathew; Francis, Isaac R.

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) wasmore » given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.« less

Anal Cancer: An Examination of Radiotherapy Strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glynne-Jones, Rob; Lim, Faye

2011-04-01

The Radiation Therapy Oncology Group 9811, ACCORD-03, and ACT II Phase III trials in anal cancer showed no benefit for cisplatin-based induction and maintenance chemotherapy, or radiation dose-escalation >59 Gy. This review examines the efficacy and toxicity of chemoradiation (CRT) in anal cancer, and discusses potential alternative radiotherapy strategies. The evidence for the review was compiled from randomized and nonrandomized trials of radiation therapy and CRT. A total of 103 retrospective/observational studies, 4 Phase I/II studies, 16 Phase II prospective studies, 2 randomized Phase II studies, and 6 Phase III trials of radiotherapy or chemoradiation were identified. There are nomore » meta-analyses based on individual patient data. A 'one-size-fits-all' approach for all stages of anal cancer is inappropriate. Early T1 tumors are probably currently overtreated, whereas T3/T4 lesions might merit escalation of treatment. Intensity-modulated radiotherapy or the integration of biological therapy may play a role in future.« less

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

A prospective pilot study on early toxicity from a simultaneously integrated boost technique for canine sinonasal tumours using image-guided intensity-modulated radiation therapy.

PubMed

Soukup, A; Meier, V; Pot, S; Voelter, K; Rohrer Bley, C

2018-05-14

In order to overcome the common local treatment failure of canine sinonasal tumours, integrated boost techniques were tried in the cobalt/orthovoltage era, but dismissed because of unacceptable early (acute) toxicity. Intriguingly, a recent calculation study of a simultaneously integrated boost (SIB) technique for sinonasal irradiation using intensity-modulated radiation therapy (IMRT) predicted theoretical feasibility. In this prospective pilot study we applied a commonly used protocol of 10 × 4.2 Gy to the planning target volume (PTV) with a 20%-SIB dose to the gross tumour volume (GTV). Our hypothesis expected this dose escalation to be clinically tolerable if applied with image-guided IMRT. We included 9 dogs diagnosed with sinonasal tumours without local/distant metastases. For treatment planning, organs at risk were contoured according to strict anatomical guidelines. Planning volume extensions (GTV/CTV/PTV) were standardized to minimize interplanner variability. Treatments were applied with rigid patient positioning and verified daily with image guidance. After radiation therapy, we set focus on early ophthalmologic complications as well as mucosal and cutaneous toxicity. Early toxicity was evaluated at week 1, 2, 3, 8 and 12 after radiotherapy. Only mild ophthalmologic complications were found. Three patients (33%) had self-limiting moderate to severe early toxicity (grade 3 mucositis) which was managed medically. No patient developed ulcerations/haemorrhage/necrosis of skin/mucosa. The SIB protocol applied with image-guided IMRT to treat canine sinonasal tumours led to clinically acceptable side effects. The suspected increased tumour control probability and the risk of late toxicity with the used dose escalation of 20% has to be further investigated. © 2018 John Wiley & Sons Ltd.

Radiation Therapy for Locally Advanced Esophageal Cancer.

PubMed

Chun, Stephen G; Skinner, Heath D; Minsky, Bruce D

2017-04-01

The treatment of locally advanced esophageal cancer is controversial. For patients who are candidates for surgical resection, multiple prospective clinical trials have demonstrated the advantages of neoadjuvant chemoradiation. For patients who are medically inoperable, definitive chemoradiation is an alternative approach with survival rates comparable to trimodality therapy. Although trials of dose escalation are ongoing, the standard radiation dose remains 50.4 Gy. Modern radiotherapy techniques such as image-guided radiation therapy with motion management and intensity-modulated radiation therapy are strongly encouraged with a planning objective to maximize conformity to the intended target volume while reducing dose delivered to uninvolved normal tissues. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer.

PubMed

López, Escarlata; Lazo, Antonio; Gutiérrez, Antonio; Arregui, Gregorio; Núñez, Isabel; Sacchetti, Antonio

2015-01-01

To evaluate the influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer patients. Precise information on the extension of prostate cancer is crucial for the choice of an appropriate therapeutic strategy. (11)C-choline positron emission tomography ((11)C-choline PET/CT) has two roles in radiation oncology (RT): (1) patient selection for treatment and (2) target volume selection and delineation. In conjunction with high-accuracy techniques, it might offer an opportunity of dose escalation and better tumour control while sparing healthy tissues. We carried out a retrospective study in order to analyse RT planning modification based on (11)C-choline PET/CT in 16 prostate cancer patients. Patients were treated with hypofractionated step-and-shoot Intensity Modulated Radiotherapy (IMRT), or Volumetric Modulated Arc Therapy (VMAT), and a daily cone-beam CT for Image Guided Radiation Therapy (IGRT). All patients underwent a (11)C-choline-PET/CT scan prior to radiotherapy. In 37.5% of cases, a re-delineation and new dose prescription occurred. Data show good preliminary clinical results in terms of biochemical control and toxicity. No gastrointestinal (GI)/genitourinary (GU) grade III toxicities were observed after a median follow-up of 9.5 months. In our experience, concerning the treatment of prostate cancer (PCa), (11)C-choline PET/CT may be helpful in radiotherapy planning, either for dose escalation or exclusion of selected sites.

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talleur, Aimee C.; Navid, Fariba; Spunt, Sheri L.

Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resectionmore » received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, P; Kuo, L; Yorke, E

Purpose: To develop a biological modeling strategy which incorporates the response observed on the mid-treatment PET/CT into a dose escalation design for adaptive radiotherapy of non-small-cell lung cancer. Method: FDG-PET/CT was acquired midway through standard fractionated treatment and registered to pre-treatment planning PET/CT to evaluate radiation response of lung cancer. Each mid-treatment PET voxel was assigned the median SUV inside a concentric 1cm-diameter sphere to account for registration and imaging uncertainties. For each voxel, the planned radiation dose, pre- and mid-treatment SUVs were used to parameterize the linear-quadratic model, which was then utilized to predict the SUV distribution after themore » full prescribed dose. Voxels with predicted post-treatment SUV≥2 were identified as the resistant target (response arm). An adaptive simultaneous integrated boost was designed to escalate dose to the resistant target as high as possible, while keeping prescription dose to the original target and lung toxicity intact. In contrast, an adaptive target volume was delineated based only on the intensity of mid-treatment PET/CT (intensity arm), and a similar adaptive boost plan was optimized. The dose escalation capability of the two approaches was compared. Result: Images of three patients were used in this planning study. For one patient, SUV prediction indicated complete response and no necessary dose escalation. For the other two, resistant targets defined in the response arm were multifocal, and on average accounted for 25% of the pre-treatment target, compared to 67% in the intensity arm. The smaller response arm targets led to a 6Gy higher mean target dose in the adaptive escalation design. Conclusion: This pilot study suggests that adaptive dose escalation to a biologically resistant target predicted from a pre- and mid-treatment PET/CT may be more effective than escalation based on the mid-treatment PET/CT alone. More plans and ultimately clinical protocols are needed to validate this approach. MSKCC has a research agreement with Varian Medical System.« less

Alcohol and violence: neuropeptidergic modulation of monoamine systems

PubMed Central

Miczek, Klaus A.; DeBold, Joseph F.; Hwa, Lara S.; Newman, Emily L.; de Almeida, Rosa M. M.

2015-01-01

Neurobiological processes underlying the epidemiologically-established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals that are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption. PMID:26285061

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brower, Jeffrey V.; Chen, Shuai; Bassetti, Michael F.

Purpose: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Methods and Materials: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. Results: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received dosesmore » >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). Conclusions: In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.« less

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012.

PubMed

Brower, Jeffrey V; Chen, Shuai; Bassetti, Michael F; Yu, Menggang; Harari, Paul M; Ritter, Mark A; Baschnagel, Andrew M

2016-12-01

To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Results of a multicentric in silico clinical trial (ROCOCO): comparing radiotherapy with photons and protons for non-small cell lung cancer.

PubMed

Roelofs, Erik; Engelsman, Martijn; Rasch, Coen; Persoon, Lucas; Qamhiyeh, Sima; de Ruysscher, Dirk; Verhaegen, Frank; Pijls-Johannesma, Madelon; Lambin, Philippe

2012-01-01

This multicentric in silico trial compares photon and proton radiotherapy for non-small cell lung cancer patients. The hypothesis is that proton radiotherapy decreases the dose and the volume of irradiated normal tissues even when escalating to the maximum tolerable dose of one or more of the organs at risk (OAR). Twenty-five patients, stage IA-IIIB, were prospectively included. On 4D F18-labeled fluorodeoxyglucose-positron emission tomography-computed tomography scans, the gross tumor, clinical and planning target volumes, and OAR were delineated. Three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) photon and passive scattered conformal proton therapy (PSPT) plans were created to give 70 Gy to the tumor in 35 fractions. Dose (de-)escalation was performed by rescaling to the maximum tolerable dose. Protons resulted in the lowest dose to the OAR, while keeping the dose to the target at 70 Gy. The integral dose (ID) was higher for 3DCRT (59%) and IMRT (43%) than for PSPT. The mean lung dose reduced from 18.9 Gy for 3DCRT and 16.4 Gy for IMRT to 13.5 Gy for PSPT. For 10 patients, escalation to 87 Gy was possible for all 3 modalities. The mean lung dose and ID were 40 and 65% higher for photons than for protons, respectively. The treatment planning results of the Radiation Oncology Collaborative Comparison trial show a reduction of ID and the dose to the OAR when treating with protons instead of photons, even with dose escalation. This shows that PSPT is able to give a high tumor dose, while keeping the OAR dose lower than with the photon modalities.

Proton therapy in clinical practice

PubMed Central

Liu, Hui; Chang, Joe Y.

2011-01-01

Radiation dose escalation and acceleration improves local control but also increases toxicity. Proton radiation is an emerging therapy for localized cancers that is being sought with increasing frequency by patients. Compared with photon therapy, proton therapy spares more critical structures due to its unique physics. The physical properties of a proton beam make it ideal for clinical applications. By modulating the Bragg peak of protons in energy and time, a conformal radiation dose with or without intensity modulation can be delivered to the target while sparing the surrounding normal tissues. Thus, proton therapy is ideal when organ preservation is a priority. However, protons are more sensitive to organ motion and anatomy changes compared with photons. In this article, we review practical issues of proton therapy, describe its image-guided treatment planning and delivery, discuss clinical outcome for cancer patients, and suggest challenges and the future development of proton therapy. PMID:21527064

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men receivedmore » CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this hypofractionation regimen.« less

Robotic crabs reveal that female fiddler crabs are sensitive to changes in male display rate.

PubMed

Mowles, Sophie L; Jennions, Michael D; Backwell, Patricia R Y

2018-01-01

Males often produce dynamic, repetitive courtship displays that can be demanding to perform and might advertise male quality to females. A key feature of demanding displays is that they can change in intensity: escalating as a male increases his signalling effort, but de-escalating as a signaller becomes fatigued. Here, we investigated whether female fiddler crabs, Uca mjoebergi , are sensitive to changes in male courtship wave rate. We performed playback experiments using robotic male crabs that had the same mean wave rate, but either escalated, de-escalated or remained constant. Females demonstrated a strong preference for escalating robots, but showed mixed responses to robots that de-escalated ('fast' to 'slow') compared to those that waved at a constant 'medium' rate. These findings demonstrate that females can discern changes in male display rate, and prefer males that escalate, but that females are also sensitive to past display rates indicative of prior vigour. © 2018 The Authors.

Safety Features of Material and Personnel Movement Devices. Module SH-25. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on safety features of material and personnel movement devices is one of 50 modules concerned with job safety and health. This module covers safe conditions and operating practices for conveyors, elevators, escalators, moving walks, manlifts, forklifts, and motorized hand trucks. Following the introduction, 10 objectives (each…

Adaptive Radiation Therapy for Localized Mesothelioma with Mediastinal Metastasis Using Helical Tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renaud, James; Yartsev, Slav; Department of Oncology, University of Western Ontario, London, Ontario

2009-10-01

The purpose of this study was to compare 2 adaptive radiotherapy strategies with helical tomotherapy. A patient having mesothelioma with mediastinal nodes was treated using helical tomotherapy with pretreatment megavoltage CT (MVCT) imaging. Gross tumor volumes (GTVs) were outlined on every MVCT study. Two alternatives for adapting the treatment were investigated: (1) keeping the prescribed dose to the targets while reducing the dose to the OARs and (2) escalating the target dose while maintaining the original level of healthy tissue sparing. Intensity modulated radiotherapy (step-and-shoot IMRT) and 3D conformal radiotherapy (3DCRT) plans for the patient were generated and compared. Themore » primary lesion and nodal mass regressed by 16.2% and 32.5%, respectively. Adapted GTVs and reduced planning target volume (PTV) margins of 4 mm after 22 fractions decrease the planned mean lung dose by 19.4%. For dose escalation, the planned prescribed doses may be increased from 50.0 to 58.7 Gy in PTV{sub 1} and from 60.0 to 70.5 Gy in PTV{sub 2}. The step-and-shoot IMRT plan was better in sparing healthy tissue but did not provide target coverage as well as the helical tomotherapy plan. The 3DCRT plan resulted in a prohibitively high planned dose to the spinal cord. MVCT studies provide information both for setup correction and plan adaptation. Improved healthy tissue sparing and/or dose escalation can be achieved by adaptive planning.« less

Hyperfractionated accelerated radiotherapy with concomitant integrated boost of 70-75 Gy in 5 weeks for advanced head and neck cancer. A phase I dose escalation study.

PubMed

Cvek, J; Kubes, J; Skacelikova, E; Otahal, B; Kominek, P; Halamka, M; Feltl, D

2012-08-01

The present study was performed to evaluate the feasibility of a new, 5-week regimen of 70-75 Gy hyperfractionated accelerated radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced, inoperable head and neck cancer. A total of 39 patients with very advanced, stage IV nonmetastatic head and neck squamous cell carcinoma (median gross tumor volume 72 ml) were included in this phase I dose escalation study. A total of 50 fractions intensity-modulated radiotherapy (IMRT) were administered twice daily over 5 weeks. Prescribed total dose/dose per fraction for planning target volume (PTV(tumor)) were 70 Gy in 1.4 Gy fractions, 72.5 Gy in 1.45 Gy fractions, and 75 Gy in 1.5 Gy fractions for 10, 13, and 16 patients, respectively. Uninvolved lymphatic nodes (PTV(uninvolved)) were irradiated with 55 Gy in 1.1 Gy fractions using the concomitant integrated boost. Acute toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade 3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery time was ≤ 9 weeks for all patients. Late toxicity was evaluated in patients in complete remission according to the RTOG/EORTC scale. No grade 3/4 late toxicity was observed. The 1-year locoregional progression-free survival was 50% and overall survival was 55%. HARTCIB (75 Gy in 5 weeks) is feasible for patients deemed unsuitable for chemoradiation. Acute toxicity was lower than predicted from radiobiological models; duration of dysphagia and confluent mucositis were particularly short. Better conformity of radiotherapy allows the use of more intensive altered fractionation schedules compared with older studies. These results suggest that further dose escalation might be possible when highly conformal techniques (e.g., stereotactic radiotherapy) are used.

Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study.

PubMed

Haslett, Kate; Franks, Kevin; Hanna, Gerard G; Harden, Susan; Hatton, Matthew; Harrow, Stephen; McDonald, Fiona; Ashcroft, Linda; Falk, Sally; Groom, Nicki; Harris, Catherine; McCloskey, Paula; Whitehurst, Philip; Bayman, Neil; Faivre-Finn, Corinne

2016-04-15

The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of 'isotoxic' radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable. Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years. The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West-Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally. NCT01836692; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

PubMed Central

Lee, Nancy Y.; Mechalakos, James G.; Nehmeh, Sadek; Lin, Zhixiong; Squire, Olivia D.; Cai, Shangde; Chan, Kelvin; Zanzonico, Pasquale B.; Greco, Carlo; Ling, Clifton C.; Humm, John L.; Schöder, Heiko

2010-01-01

Purpose Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTVh) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTVh increases the tumor control probability. This study examined the feasibility of fluorine-18–labeled fluoromisonidazole positron emission tomography/computed tomography (18F-FMISO PET/CT)–guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients. Methods and Materials 18F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and 18F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated 18F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate 18F-FMISO PET/CT-guided IMRT plans. Results The heterogeneous distribution of 18F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing 18F-FMISO PET/CT–guided IMRT for 10 HNC patients achieved 84 Gy to the GTVh and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTVh for 2 patients and were successful in 1, with normal tissue sparing. Conclusion It was feasible to dose escalate the GTVh to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients. PMID:17869020

Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

NASA Astrophysics Data System (ADS)

Gutierrez, Alonso Navar

2007-12-01

Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the feasibility of delivering a simultaneously integrated subvolume boost to canine nasal tumors and was found to dramatically increase estimated 1-year tumor control probability (TCP) without increasing the dose to the eyes, so as to preserve vision, and to the brain, so as to prevent neuropathy.

Technological advances in radiotherapy of rectal cancer: opportunities and challenges.

PubMed

Appelt, Ane L; Sebag-Montefiore, David

2016-07-01

This review summarizes the available evidence for the use of modern radiotherapy techniques for chemoradiotherapy for rectal cancer, with specific focus on intensity-modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) techniques. The dosimetric benefits of IMRT and VMAT are well established, but prospective clinical studies are limited, with phase I-II studies only. Recent years have seen the publication of a few larger prospective patient series as well as some retrospective cohorts, several of which include much needed late toxicity data. Overall results are encouraging, as toxicity levels - although varying across reports - appear lower than for 3D conformal radiotherapy. Innovative treatment techniques and strategies which may be facilitated by the use of IMRT/VMAT include simultaneously integrated tumour boost, adaptive treatment, selective sparing of specific organs to enable chemotherapy escalation, and nonsurgical management. Few prospective studies of IMRT and VMAT exist, which causes uncertainty not just in regards to the clinical benefit of these technologies but also in the optimal use. The priority for future research should be subgroups of patients who might receive relatively greater benefit from innovative treatment techniques, such as patients receiving chemoradiotherapy with definitive intent and patients treated with dose escalation.

Escalation of Commitment in the Surgical ICU.

PubMed

Braxton, Carla C; Robinson, Celia N; Awad, Samir S

2017-04-01

Escalation of commitment is a business term that describes the continued investment of resources into a project even after there is objective evidence of the project's impending failure. Escalation of commitment may be a contributor to high healthcare costs associated with critically ill patients as it has been shown that, despite almost certain futility, most ICU costs are incurred in the last week of life. Our objective was to determine if escalation of commitment occurs in healthcare settings, specifically in the surgical ICU. We hypothesize that factors previously identified in business and organizational psychology literature including self-justification, accountability, sunk costs, and cognitive dissonance result in escalation of commitment behavior in the surgical ICU setting resulting in increased utilization of resources and cost. A descriptive case study that illustrates common ICU narratives in which escalation of commitment can occur. In addition, we describe factors that are thought to contribute to escalation of commitment behaviors. Escalation of commitment behavior was observed with self-justification, accountability, and cognitive dissonance accounting for the majority of the behavior. Unlike in business decisions, sunk costs was not as evident. In addition, modulating factors such as personality, individual experience, culture, and gender were identified as contributors to escalation of commitment. Escalation of commitment occurs in the surgical ICU, resulting in significant expenditure of resources despite a predicted and often known poor outcome. Recognition of this phenomenon may lead to actions aimed at more rational decision making and may contribute to lowering healthcare costs. Investigation of objective measures that can help aid decision making in the surgical ICU is warranted.

Methods, safety, and early clinical outcomes of dose escalation using simultaneous integrated and sequential boosts in patients with locally advanced gynecologic malignancies.

PubMed

Boyle, John; Craciunescu, Oana; Steffey, Beverly; Cai, Jing; Chino, Junzo

2014-11-01

To evaluate the safety of dose escalated radiotherapy using a simultaneous integrated boost technique in patients with locally advanced gynecological malignancies. Thirty-nine women with locally advanced gynecological malignancies were treated with intensity modulated radiation therapy utilizing a simultaneous integrated boost (SIB) technique for gross disease in the para-aortic and/or pelvic nodal basins, sidewall extension, or residual primary disease. Women were treated to 45Gy in 1.8Gy fractions to elective nodal regions. Gross disease was simultaneously treated to 55Gy in 2.2Gy fractions (n=44 sites). An additional sequential boost of 10Gy in 2Gy fractions was delivered if deemed appropriate (n=29 sites). Acute and late toxicity, local control in the treated volumes (LC), overall survival (OS), and distant metastases (DM) were assessed. All were treated with a SIB to a dose of 55Gy. Twenty-four patients were subsequently treated with a sequential boost to a median dose of 65Gy. Median follow-up was 18months. Rates of acute>grade 2 gastrointestinal (GI), genitourinary (GU), and hematologic (heme) toxicities were 2.5%, 0%, and 30%, respectively. There were no grade 4 acute toxicities. At one year, grade 1-2 late GI toxicities were 24.5%. There were no grade 3 or 4 late GI toxicities. Rates of grade 1-2 late GU toxicities were 12.7%. There were no grade 3 or 4 late GU toxicities. Dose escalated radiotherapy using a SIB results in acceptable rates of acute toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, Sunil, E-mail: skrishnan@mdanderson.org; Chadha, Awalpreet S.; Suh, Yelin

2016-03-15

Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume wasmore » treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.« less

Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls.

PubMed

Mendenhall, William M; Amdur, Robert J; Palta, Jatinder R

2006-06-10

The purpose of this article is to review the role of intensity-modulated radiotherapy (IMRT) in the standard management of patients with head and neck cancer through a critical review of the pertinent literature. IMRT may result in a dose distribution that is more conformal than that achieved with three-dimensional conformal radiotherapy (3D CRT), allowing dose reduction to normal structures and thus decreasing toxicity and possibly enhancing locoregional control through dose escalation. Disadvantages associated with IMRT include increased risk of a marginal miss, decreased dose homogeneity, increased total body dose, and increased labor and expense. Outcomes data after IMRT are limited, and follow-up is relatively short. Locoregional control rates appear to be comparable to those achieved with 3D CRT and, depending on the location and extent of the tumor, late toxicity may be lower. Despite limited data on clinical outcomes, IMRT has been widely adopted as a standard technique in routine practice and clinical trials. The use of IMRT involves a learning curve for the practitioner and will continue to evolve, requiring continuing education and monitoring of outcomes from routine practice. Additional standards pertaining to a variety of issues, including target definitions and dose specification, need to be developed. Phase III trials will better define the role of IMRT in coming years.

External Beam Radiotherapy for Prostate Cancer Patients on Anticoagulation Therapy: How Significant is the Bleeding Toxicity?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choe, Kevin S.; Jani, Ashesh B.; Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.ed

Purpose: To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy. Methods and Materials: The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits. Results: With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receivingmore » AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >=70 Gy was <10% or the rectum receiving >=50 Gy was <50%. Conclusion: Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.« less

Postoperative Intensity-Modulated Radiotherapy in Low-Risk Endometrial Cancers: Final Results of a Phase I Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.i; Cilla, Savino M.P.; Ferrandina, Gabriella

2010-04-15

Purpose: To determine the maximum tolerated dose of short-course radiotherapy (intensity-modulated radiotherapy technique) to the upper two thirds of the vagina in endometrial cancers with low risk of local recurrence. Patients and Methods: A Phase I clinical trial was performed. Eligible patients had low-risk resected primary endometrial adenocarcinomas. Radiotherapy was delivered in 5 fractions over 1 week. The planning target volume was the clinical target volume plus 5 mm. The clinical target volume was defined as the upper two thirds of the vagina as evidenced at CT simulation by a vaginal radio-opaque device. The planning target volume was irradiated bymore » a seven-field intensity-modulated radiotherapy technique, planned by the Plato Sunrise inverse planning system. A first cohort of 6 patients received 25 Gy (5-Gy fractions), and a subsequent cohort received 30 Gy (6-Gy fractions). The Common Toxicity Criteria scale, version 3.0, was used to score toxicity. Results: Twelve patients with endometrial cancer were enrolled. Median age was 58 years (range, 49-74 years). Pathologic stage was IB (83.3%) and IC (16.7%). Median tumor size was 30 mm (range, 15-50 mm). All patients completed the prescribed radiotherapy. No patient experienced a dose-limiting toxicity at the first level, and the radiotherapy dose was escalated from 25 to 30 Gy. No patients at the second dose level experienced dose-limiting toxicity. The most common Grade 2 toxicity was gastrointestinal, which was tolerable and manageable. Conclusions: The maximum tolerated dose of short-course radiotherapy was 30 Gy at 6 Gy per fraction. On the basis of this result, we are conducting a Phase II study with radiotherapy delivered at 30 Gy.« less

De-escalation, adequacy of antibiotic therapy and culture positivity in septic patients: an observational study.

PubMed

Moraes, Rafael Barberena; Guillén, Julián Alberto Viteri; Zabaleta, William Javier Castillo; Borges, Flavia Kessler

2016-09-01

To evaluate the prevalence of antibiotic de-escalation in patients diagnosed with severe sepsis or septic shock at a public academic tertiary hospital and to evaluate antibiotic adequacy and culture positivity. The prevalence of antibiotic de-escalation, the adequacy of antibiotic treatment and the rates of culture positivity were analyzed in patients with severe sepsis and septic shock between April and December 2013 at an intensive care unit in a tertiary university hospital. Among the 224 patients included in the study, de-escalation was appropriate in 66 patients (29.4%) but was implemented in 44 patients (19.6%). Among the patients who underwent de-escalation, half experienced narrowing of the antimicrobial spectrum. The mortality rate was 56.3%, with no differences between the patients with or without de-escalation (56.8% versus 56.1%; p = 0.999) nor in the length of hospital stay. Empirical antibiotic therapy was appropriate in 89% of cases. Microorganisms were isolated from total cultures in 30% of cases and from blood cultures in 26.3% of cases. The adequacy rate of empirical antibiotic therapy was high, reflecting an active institutional policy of monitoring epidemiological profiles and institutional protocols on antimicrobial use. However, antibiotic de-escalation could have been implemented in a greater number of patients. De-escalation did not affect mortality rates.

Interfractional Dose Variations in Intensity-Modulated Radiotherapy With Breath-Hold for Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Mitsuhiro; Shibuya, Keiko, E-mail: kei@kuhp.kyoto-u.ac.jp; Nakamura, Akira

2012-04-01

Purpose: To investigate the interfractional dose variations for intensity-modulated radiotherapy (RT) combined with breath-hold (BH) at end-exhalation (EE) for pancreatic cancer. Methods and Materials: A total of 10 consecutive patients with pancreatic cancer were enrolled. Each patient was fixed in the supine position on an individualized vacuum pillow with both arms raised. Computed tomography (CT) scans were performed before RT, and three additional scans were performed during the course of chemoradiotherapy using a conventional RT technique. The CT data were acquired under EE-BH conditions (BH-CT) using a visual feedback technique. The intensity-modulated RT plan, which used five 15-MV coplanar ports,more » was designed on the initial BH-CT set with a prescription dose of 39 Gy at 2.6 Gy/fraction. After rigid image registration between the initial and subsequent BH-CT scans, the dose distributions were recalculated on the subsequent BH-CT images under the same conditions as in planning. Changes in the dose-volume metrics of the gross tumor volume (GTV), clinical target volume (CTV = GTV + 5 mm), stomach, and duodenum were evaluated. Results: For the GTV and clinical target volume (CTV), the 95th percentile of the interfractional variations in the maximal dose, mean dose, dose covering 95% volume of the region of structure, and percentage of the volume covered by the 90% isodose line were within {+-}3%. Although the volume covered by the 39 Gy isodose line for the stomach and duodenum did not exceed 0.1 mL at planning, the volume covered by the 39 Gy isodose line for these structures was up to 11.4 cm{sup 3} and 1.8 cm{sup 3}, respectively. Conclusions: Despite variations in the gastrointestinal state and abdominal wall position at EE, the GTV and CTV were mostly ensured at the planned dose, with the exception of 1 patient. Compared with the duodenum, large variations in the stomach volume receiving high-dose radiation were observed, which might be beyond the negligible range in achieving dose escalation with intensity-modulated RT combined with BH at EE.« less

A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu; Ayala, Deandra; Jensen, Courtney

2012-02-01

Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patientsmore » experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.« less

Prevention and reversal of social stress-escalated cocaine self-administration in mice by intra-VTA CRFR1 antagonism.

PubMed

Han, Xiao; DeBold, Joseph F; Miczek, Klaus A

2017-09-01

A history of brief intermittent social defeat stress can escalate cocaine self-administration and induce long-term adaptations in the mesolimbic dopamine system. Extra-hypothalamic corticotrophin releasing factor (CRF) has been shown to be closely associated with stress-induced escalation of drug use. How repeated stress modulates CRF release in the ventral tegmental area (VTA) and the roles of CRF receptors during different phases of stress-induced cocaine self-administration remain to be defined. The current study examines the roles of CRF and CRF receptor 1 (CRFR1) in escalated intravenous cocaine self-administration after exposure to social defeat stress in mice. First, CRFR1 antagonist (CP 376,395, 15 mg/kg, i.p.) given 30 min prior to each social defeat episode prevented later escalated cocaine self-administration. When CP 376,395 (5 and 15 mg/kg, i.p.) was administered 10 days after the last episode of social stress, the escalation of cocaine intake was dose-dependently reversed. Moreover, socially defeated mice showed increased CRF release in the VTA compared to controls. To further explore the role of CRFR1, CP 376,395 (0.5 and 1 μg/0.2 μl) was infused directly into the VTA before the cocaine self-administration session. Intra-VTA antagonism of CRFR1 was sufficient to reverse social defeat stress-escalated cocaine self-administration. These findings suggest that CRF and CRFR1 exert multiple roles in the response to social stress that are relevant to escalated cocaine self-administration.

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer

PubMed Central

Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

2014-01-01

Purpose Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Methods and materials Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. Conclusion There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for the treatment of prostate cancer. PMID:25210465

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer.

PubMed

Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

2014-01-01

Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for the treatment of prostate cancer.

Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaidar-Person, Orit; Roach, Mack; Créhange, Gilles, E-mail: gcrehange@cgfl.fr

2013-07-15

Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have amore » high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer.« less

An individualized radiation dose escalation trial in non-small cell lung cancer based on FDG-PET imaging.

PubMed

Wanet, Marie; Delor, Antoine; Hanin, François-Xavier; Ghaye, Benoît; Van Maanen, Aline; Remouchamps, Vincent; Clermont, Christian; Goossens, Samuel; Lee, John Aldo; Janssens, Guillaume; Bol, Anne; Geets, Xavier

2017-10-01

The aim of the study was to assess the feasibility of an individualized 18F fluorodeoxyglucose positron emission tomography (FDG-PET)-guided dose escalation boost in non-small cell lung cancer (NSCLC) patients and to assess its impact on local tumor control and toxicity. A total of 13 patients with stage II-III NSCLC were enrolled to receive a dose of 62.5 Gy in 25 fractions to the CT-based planning target volume (PTV; primary turmor and affected lymph nodes). The fraction dose was increased within the individual PET-based PTV (PTV PET ) using intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) until the predefined organ-at-risk (OAR) threshold was reached. Tumor response was assessed during follow-up by means of repeat FDG-PET/computed tomography. Acute and late toxicity were recorded and classified according to the CTCAE criteria (Version 4.0). Local progression-free survival was determined using the Kaplan-Meier method. The average dose to PTV PET reached 89.17 Gy for peripheral and 75 Gy for central tumors. After a median follow-up period of 29 months, seven patients were still alive, while six had died (four due to distant progression, two due to grade 5 toxicity). Local progression was seen in two patients in association with further recurrences. One and 2-year local progression free survival rates were 76.9% and 52.8%, respectively. Three cases of acute grade 3 esophagitis were seen. Two patients with central tumors developed late toxicity and died due to severe hemoptysis. These results suggest that a non-uniform and individualized dose escalation based on FDG-PET in IMRT delivery is feasible. The doses reached were higher in patients with peripheral compared to central tumors. This strategy enables good local control to be achieved at acceptable toxicity rates. However, dose escalation in centrally located tumors with direct invasion of mediastinal organs must be performed with great caution in order to avoid severe late toxicity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castle, Katherine O., E-mail: kocastle@mdanderson.org; Hoffman, Karen E.; Levy, Lawrence B.

Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis basedmore » on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF.« less

Brain Serotonin Receptors and Transporters: Initiation vs. Termination of Escalated Aggression

PubMed Central

Takahashi, Aki; Quadros, Isabel M.; de Almeida, Rosa M. M.; Miczek, Klaus A.

2013-01-01

Rationale Recent findings have shown a complexly regulated 5-HT system as it is linked to different kinds of aggression. Objective We focus on (1) phasic and tonic changes of 5-HT and (2) state and trait of aggression, and emphasize the different receptor subtypes, their role in specific brain regions, feed-back regulation and modulation by other amines, acids and peptides. Results New pharmacological tools differentiate the first three 5-HT receptor families and their modulation by GABA, glutamate and CRF. Activation of 5-HT1A, 5-HT1B and 5-HT2A/2C receptors in mesocorticolimbic areas, reduce species-typical and other aggressive behaviors. In contrast, agonists at 5-HT1A and 5-HT1B receptors in the medial prefrontal cortex or septal area can increase aggressive behavior under specific conditions. Activation of serotonin transporters reduce mainly pathological aggression. Genetic analyses of aggressive individuals have identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or indirectly (e.g., Neuropeptide Y, αCaMKII, NOS, BDNF). Dysfunction in genes for MAOA escalates pathological aggression in rodents and humans, particularly in interaction with specific experiences. Conclusions Feedback to autoreceptors of the 5-HT1 family and modulation via heteroreceptors are important in the expression of aggressive behavior. Tonic increase of the 5-HT2 family expression may cause escalated aggression, whereas the phasic increase of 5-HT2 receptors inhibits aggressive behaviors. Polymorphisms in the genes of 5-HT transporters or rate-limiting synthetic and metabolic enzymes of 5-HT modulate aggression, often requiring interaction with the rearing environment. PMID:20938650

The Role of Sweet Taste in Satiation and Satiety

PubMed Central

Low, Yu Qing; Lacy, Kathleen; Keast, Russell

2014-01-01

Increased energy consumption, especially increased consumption of sweet energy-dense food, is thought to be one of the main contributors to the escalating rates in overweight individuals and obesity globally. The individual’s ability to detect or sense sweetness in the oral cavity is thought to be one of many factors influencing food acceptance, and therefore, taste may play an essential role in modulating food acceptance and/or energy intake. Emerging evidence now suggests that the sweet taste signaling mechanisms identified in the oral cavity also operate in the gastrointestinal system and may influence the development of satiety. Understanding the individual differences in detecting sweetness in both the oral and gastrointestinal system towards both caloric sugar and high intensity sweetener and the functional role of the sweet taste system may be important in understanding the reasons for excess energy intake. This review will summarize evidence of possible associations between the sweet taste mechanisms within the oral cavity, gastrointestinal tract and the brain systems towards both caloric sugar and high intensity sweetener and sweet taste function, which may influence satiation, satiety and, perhaps, predisposition to being overweight and obesity. PMID:25184369

Dose-Escalated Robotic SBRT for Stage I–II Prostate Cancer

PubMed Central

Meier, Robert

2015-01-01

Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I–II prostate cancer. PMID:25905037

Phase I study of icotinib, an EGFR tyrosine kinase inhibitor combined with IMRT in nasopharyngeal carcinoma.

PubMed

Hu, Wei; Wang, Wei; Yang, Peinong; Zhou, Chao; Yang, Weifang; Wu, Bo; Lu, Hongsheng; Yang, Haihua

2015-01-01

Epidermal growth factor receptor (EGFR) is a new target for nasopharyngeal carcinoma (NPC) therapy. This prospective phase I study sought to determine the safety and recommended phase II dose of icotinib, a novel highly selective oral EGFR tyrosine kinase inhibitor, in combination with intensity-modulated radiotherapy (IMRT) in patients with NPC. Eligible patients with NPC received escalating doses of icotinib during IMRT. We treated six patients at a particular dose level until the maximum tolerated dose (MTD) was determined. The starting dose was 125 mg, once-daily and the dose was escalated to another level 125 mg, twice- and thrice- daily, until dose-limiting toxicity (DLT) occurred in two or more patients at a dose level. Expression and mutation analysis of EGFR were performed in all cases. A total of twelve patients were enrolled. Three patients experienced DLT (250 mg/day cohort) and MTD was 125 mg/day. Mucositis toxicity appears to be the major DLT. While EGFR expression in tumor tissue was detected in 75% (9/12) patients, EGFR mutation was detected in 16.67% (1/6) patients in 125 mg/day cohort, and 50% (3/6) in 250 mg/day cohort. The combination of icotinib (125 mg/day) and IMRT in patients with locally NPC had an acceptable safety profile and was well tolerated.

The development of an inherent safety approach to the prevention of domino accidents.

PubMed

Cozzani, Valerio; Tugnoli, Alessandro; Salzano, Ernesto

2009-11-01

The severity of industrial accidents in which a domino effect takes place is well known in the chemical and process industry. The application of an inherent safety approach for the prevention of escalation events leading to domino accidents was explored in the present study. Reference primary scenarios were analyzed and escalation vectors were defined. Inherent safety distances were defined and proposed as a metric to express the intensity of the escalation vectors. Simple rules of thumb were presented for a preliminary screening of these distances. Swift reference indices for layout screening with respect to escalation hazard were also defined. Two case studies derived from existing layouts of oil refineries were selected to understand the potentialities coming from the application in the methodology. The results evidenced that the approach allows a first comparative assessment of the actual domino hazard in a layout, and the identification of critical primary units with respect to escalation events. The methodology developed also represents a useful screening tool to identify were to dedicate major efforts in the design of add-on measures, optimizing conventional passive and active measures for the prevention of severe domino accidents.

A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer.

PubMed

Reynolds, Kerry Lynn; Bedard, Philippe L; Lee, Se-Hoon; Lin, Chia-Chi; Tabernero, Josep; Alsina, Maria; Cohen, Ezra; Baselga, José; Blumenschein, George; Graham, Donna M; Garrido-Laguna, Ignacio; Juric, Dejan; Sharma, Sunil; Salgia, Ravi; Seroutou, Abdelkader; Tian, Xianbin; Fernandez, Rose; Morozov, Alex; Sheng, Qing; Ramkumar, Thiruvamoor; Zubel, Angela; Bang, Yung-Jue

2017-09-12

Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. This open-label, dose-finding study comprised dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer. During dose escalation, patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles. An adaptive Bayesian logistic regression model was used to guide dose escalation and establish the RDE. Exploratory pharmacodynamic tumor studies evaluated modulation of HER3 signaling. Patients received LJM716 3-40 mg/kg QW and 20 mg/kg Q2W (54 patients; 36 patients at 40 mg/kg QW). No dose-limiting toxicities (DLTs) were reported during dose-escalation. One patient experienced two DLTs (diarrhea, hypokalemia [both grade 3]) in the expansion phase. The RDE was 40 mg/kg QW, providing drug levels above the preclinical minimum effective concentration. One patient with gastric cancer had an unconfirmed partial response; 17/54 patients had stable disease, two lasting >30 weeks. Down-modulation of phospho-HER3 was observed in paired tumor samples. LJM716 was well tolerated; the MTD was not reached, and the RDE was 40 mg/kg QW. Further development of LJM716 is ongoing. Clinicaltrials.gov registry number NCT01598077 (registered on 4 May, 2012).

Internal States and Behavioral Decision-Making: Toward an Integration of Emotion and Cognition.

PubMed

Kennedy, Ann; Asahina, Kenta; Hoopfer, Eric; Inagaki, Hidehiko; Jung, Yonil; Lee, Hyosang; Remedios, Ryan; Anderson, David J

2014-01-01

Social interactions, such as an aggressive encounter between two conspecific males or a mating encounter between a male and a female, typically progress from an initial appetitive or motivational phase, to a final consummatory phase. This progression involves both changes in the intensity of the animals' internal state of arousal or motivation and sequential changes in their behavior. How are these internal states, and their escalating intensity, encoded in the brain? Does this escalation drive the progression from the appetitive/motivational to the consummatory phase of a social interaction and, if so, how are appropriate behaviors chosen during this progression? Recent work on social behaviors in flies and mice suggests possible ways in which changes in internal state intensity during a social encounter may be encoded and coupled to appropriate behavioral decisions at appropriate phases of the interaction. These studies may have relevance to understanding how emotion states influence cognitive behavioral decisions at higher levels of brain function. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients.

PubMed

De Meerleer, Gert; Vakaet, Luc; Meersschout, Sabine; Villeirs, Geert; Verbaeys, Antony; Oosterlinck, Wim; De Neve, Wilfried

2004-11-01

Dose escalation improves local control in prostate cancer. At Ghent University Hospital, intensity-modulated radiotherapy (IMRT) is used to increase the dose to the prostate and/or seminal vesicles. We report on acute toxicity in 114 patients who received IMRT for prostate cancer. Intensity-modulated radiotherapy was initiated after approval of our ethics committee. A class solution was used to plan all cases. Three beams (gantry 0 degrees , 116 degrees , and 244 degrees ) and anatomy-based segmentation were used to create an intensity-modulated dose distribution. Maximal rectal dose was set at 2 Gy per fraction. Detailed dose-volume histograms for all relevant structures were present. For all patients, we determined the pretreatment morbidity by a detailed preradiotherapy, in-house developed symptom scale. All patients were treated with 18 MV photons of an Elekta linear accelerator. Patients were seen on a weekly basis during treatment, and 1 month (M1) and 3 months (M3) thereafter. The registration of acute toxicity was standardized by a fixed questionnaire. The Radiation Therapy Oncology Group (RTOG) toxicity scale served as a basis, but additional symptoms, such as rectal blood loss, urgency, and incontinence, were scored as well. All 114 IMRT plans were delivered successfully without any interruption or technical problem. Daily treatment time was always less than 8 min and less than 6 min in 90% of the cases. Grade 1 and Grade 2 gastrointestinal (GI) toxicities were observed in 44% and 29% of the patients, respectively, during the whole period. If only the RTOG scale was used, Grade 1 and Grade 2 GI toxicities were noted in 39% and 27% of the patients, respectively, leaving 34% free of acute RTOG-scaled toxicity. Grade 3 genitourinary (GU) toxicity was seen in 8 patients (7%), all but 1 during treatment. Grade 2 and Grade 1 GU toxicities were seen in 36% and 47% of the patients, respectively, leaving only 10% free of acute GU toxicity. Anatomy-based IMRT to treat prostate cancer is incorporated into our daily routine without any problem. Acute toxicity is very low. Most of the recorded symptoms decrease over time, except for GI urgency and incontinence. The incorporation of additional symptoms makes the scoring more detailed.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuong, Michael D.; Hallemeier, Christopher L.; Jabbour, Salma K.

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with protonmore » beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.« less

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

PubMed

Chuong, Michael D; Hallemeier, Christopher L; Jabbour, Salma K; Yu, Jen; Badiyan, Shahed; Merrell, Kenneth W; Mishra, Mark V; Li, Heng; Verma, Vivek; Lin, Steven H

2016-05-01

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. Copyright © 2016 Elsevier Inc. All rights reserved.

Advances in radiotherapy techniques and delivery for non-small cell lung cancer: benefits of intensity-modulated radiation therapy, proton therapy, and stereotactic body radiation therapy

PubMed Central

Diwanji, Tejan P.; Mohindra, Pranshu; Vyfhuis, Melissa; Snider, James W.; Kalavagunta, Chaitanya; Mossahebi, Sina; Yu, Jen; Feigenberg, Steven

2017-01-01

The 21st century has seen several paradigm shifts in the treatment of non-small cell lung cancer (NSCLC) in early-stage inoperable disease, definitive locally advanced disease, and the postoperative setting. A key driver in improvement of local disease control has been the significant evolution of radiation therapy techniques in the last three decades, allowing for delivery of definitive radiation doses while limiting exposure of normal tissues. For patients with locally-advanced NSCLC, the advent of volumetric imaging techniques has allowed a shift from 2-dimensional approaches to 3-dimensional conformal radiation therapy (3DCRT). The next generation of 3DCRT, intensity-modulated radiation therapy and volumetric-modulated arc therapy (VMAT), have enabled even more conformal radiation delivery. Clinical evidence has shown that this can improve the quality of life for patients undergoing definitive management of lung cancer. In the early-stage setting, conventional fractionation led to poor outcomes. Evaluation of altered dose fractionation with the previously noted technology advances led to advent of stereotactic body radiation therapy (SBRT). This technique has dramatically improved local control and expanded treatment options for inoperable, early-stage patients. The recent development of proton therapy has opened new avenues for improving conformity and the therapeutic ratio. Evolution of newer proton therapy techniques, such as pencil-beam scanning (PBS), could improve tolerability and possibly allow reexamination of dose escalation. These new progresses, along with significant advances in systemic therapies, have improved survival for lung cancer patients across the spectrum of non-metastatic disease. They have also brought to light new challenges and avenues for further research and improvement. PMID:28529896

With a little help from my kin: barn swallow nestlings modulate solicitation of parental care according to nestmates' need.

PubMed

Romano, Andrea; Caprioli, M; Boncoraglio, G; Saino, N; Rubolini, D

2012-09-01

In altricial species, offspring competing for access to limiting parental resources (e.g. food) are selected to achieve an optimal balance between the costs of scrambling for food, the benefits of being fed and the indirect costs of subtracting food to relatives. As the marginal benefits of acquiring additional food decrease with decreasing levels of need, satiated offspring should be prone to favour access to food by their needy kin, thus enhancing their own indirect fitness, while concomitantly reducing costs of harsh competition with hungry broodmates. We tested this prediction in feeding trials of barn swallow (Hirundo rustica) nestlings by comparing begging behaviour and food intake of two similar-sized nestmates, one of which was food-deprived (FD). Non-food-deprived (NFD) offspring modulated begging intensity depending on their nestmate's need: when competing with FD nestmates, NFD nestlings reduced both the intensity and frequency of begging displays compared to themselves in the control trial before food deprivation. Hence, NFD nestlings reduced their competitiveness to the advantage of FD nestmates, which obtained more feedings and showed a threefold larger increase in body mass. Moderation of individual selfishness can therefore be adaptive in the presence of a needier kin, because the indirect fitness benefits of promoting its condition can outweigh the costs of forgoing being fed, and because it limits the cost of begging escalation against a vigorous competitor. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

The support-control continuum: An investigation of staff perspectives on factors influencing the success or failure of de-escalation techniques for the management of violence and aggression in mental health settings.

PubMed

Price, Owen; Baker, John; Bee, Penny; Lovell, Karina

2018-01-01

De-escalation techniques are recommended to manage violence and aggression in mental health settings yet restrictive practices continue to be frequently used. Barriers and enablers to the implementation and effectiveness of de-escalation techniques in practice are not well understood. To obtain staff descriptions of de-escalation techniques currently used in mental health settings and explore factors perceived to influence their implementation and effectiveness. Qualitative, semi-structured interviews and Framework Analysis. Five in-patient wards including three male psychiatric intensive care units, one female acute ward and one male acute ward in three UK Mental Health NHS Trusts. 20 ward-based clinical staff. Individual semi-structured interviews were digitally recorded, transcribed verbatim and analysed using a qualitative data analysis software package. Participants described 14 techniques used in response to escalated aggression applied on a continuum between support and control. Techniques along the support-control continuum could be classified in three groups: 'support' (e.g. problem-solving, distraction, reassurance) 'non-physical control' (e.g. reprimands, deterrents, instruction) and 'physical control' (e.g. physical restraint and seclusion). Charting the reasoning staff provided for technique selection against the described behavioural outcome enabled a preliminary understanding of staff, patient and environmental influences on de-escalation success or failure. Importantly, the more coercive 'non-physical control' techniques are currently conceptualised by staff as a feature of de-escalation techniques, yet, there was evidence of a link between these and increased aggression/use of restrictive practices. Risk was not a consistent factor in decisions to adopt more controlling techniques. Moral judgements regarding the function of the aggression; trial-and-error; ingrained local custom (especially around instruction to low stimulus areas); knowledge of the patient; time-efficiency and staff anxiety had a key role in escalating intervention. This paper provides a new model for understanding staff intervention in response to escalated aggression, a continuum between support and control. It further provides a preliminary explanatory framework for understanding the relationship between patient behaviour, staff response and environmental influences on de-escalation success and failure. This framework reveals potentially important behaviour change targets for interventions seeking to reduce violence and use of restrictive practices through enhanced de-escalation techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-C-BRB-02: Automatic Planning as a Potential Strategy for Dose Escalation for Pancreas SBRT?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, S; Zheng, D; Ma, R

Purpose: Stereotactic body radiation therapy (SBRT) has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly radiosensitive normal tissues usually causes the labor-intensive planning process, and may impede further escalation of the prescription dose. The present study evaluates the potential of an automatic planning system as a dose escalation strategy. Methods: Ten pancreatic cancer patients treated with SBRT were studied retrospectively. SBRT was delivered over 5 consecutive fractions with 6 ∼ 8Gy/fraction. Two plans were generated by Pinnacle Auto-Planning with the original prescription and escalated prescription, respectively. Escalated prescriptionmore » adds 1 Gy/fraction to the original prescription. Manually-created planning volumes were excluded in the optimization goals in order to assess the planning efficiency and quality simultaneously. Critical organs with closest proximity were used to determine the plan normalization to ensure the OAR sparing. Dosimetric parameters including D100, and conformity index (CI) were assessed. Results: Auto-plans directly generate acceptable plans for 70% of the cases without necessity of further improvement, and two more iterations at most are necessary for the rest of the cases. For the pancreas SBRT plans with the original prescription, autoplans resulted in favorable target coverage and PTV conformity (D100 = 96.3% ± 1.48%; CI = 0.88 ± 0.06). For the plans with the escalated prescriptions, no significant target under-dosage was observed, and PTV conformity remains reasonable (D100 = 93.3% ± 3.8%, and CI = 0.84 ± 0.05). Conclusion: Automatic planning, without substantial human-intervention process, results in reasonable PTV coverage and PTV conformity on the premise of adequate OAR sparing for the pancreas SBRT plans with escalated prescription. The results highlight the potential of autoplanning as a dose escalation strategy for pancreas SBRT treatment planning. Further investigations with a larger number of patients are necessary. The project is partially supported by Philips Medical Systems.« less

Ventilator-associated pneumonia: the influence of bacterial resistance, prescription errors, and de-escalation of antimicrobial therapy on mortality rates.

PubMed

Souza-Oliveira, Ana Carolina; Cunha, Thúlio Marquez; Passos, Liliane Barbosa da Silva; Lopes, Gustavo Camargo; Gomes, Fabiola Alves; Röder, Denise Von Dolinger de Brito

2016-01-01

Ventilator-associated pneumonia is the most prevalent nosocomial infection in intensive care units and is associated with high mortality rates (14-70%). This study evaluated factors influencing mortality of patients with Ventilator-associated pneumonia (VAP), including bacterial resistance, prescription errors, and de-escalation of antibiotic therapy. This retrospective study included 120 cases of Ventilator-associated pneumonia admitted to the adult adult intensive care unit of the Federal University of Uberlândia. The chi-square test was used to compare qualitative variables. Student's t-test was used for quantitative variables and multiple logistic regression analysis to identify independent predictors of mortality. De-escalation of antibiotic therapy and resistant bacteria did not influence mortality. Mortality was 4 times and 3 times higher, respectively, in patients who received an inappropriate antibiotic loading dose and in patients whose antibiotic dose was not adjusted for renal function. Multiple logistic regression analysis revealed the incorrect adjustment for renal function was the only independent factor associated with increased mortality. Prescription errors influenced mortality of patients with Ventilator-associated pneumonia, underscoring the challenge of proper Ventilator-associated pneumonia treatment, which requires continuous reevaluation to ensure that clinical response to therapy meets expectations. Copyright © 2016. Published by Elsevier Editora Ltda.

Interactive Book Reading to Accelerate Word Learning by Kindergarten Children with Specific Language Impairment: Identifying an Adequate Intensity and Variation in Treatment Response

ERIC Educational Resources Information Center

Storkel, Holly L.; Voelmle, Krista; Fierro, Veronica; Flake, Kelsey; Fleming, Kandace K.; Romine, Rebecca Swinburne

2017-01-01

Purpose: This study sought to identify an adequate intensity of interactive book reading for new word learning by children with specific language impairment (SLI) and to examine variability in treatment response. Method: An escalation design adapted from nontoxic drug trials (Hunsberger, Rubinstein, Dancey, & Korn, 2005) was used in this Phase…

Louisiana mid-cycle survey shows change in forests resource trends

Treesearch

Charles E. Thomas; Carl V. Bylin

1982-01-01

Because costs of doing surveys are escalating rapidly, and both dollars and manpower are scarce resources, a low-intensity survey for the mid-cycle inventory may be the answer to timely monitoring of state resource trends.

Advanced techniques in neoadjuvant radiotherapy allow dose escalation without increased dose to the organs at risk : Planning study in esophageal carcinoma.

PubMed

Fakhrian, K; Oechsner, M; Kampfer, S; Schuster, T; Molls, M; Geinitz, H

2013-04-01

The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive ≥ 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher doses through advanced techniques in the neoadjuvant treatment of LAEC.

S-1 chemotherapy and intensity-modulated radiotherapy after D1/D2 lymph node dissection in patients with node-positive gastric cancer: a phase I/II study.

PubMed

Wang, X; Zhao, D B; Yang, L; Chi, Y; Tang, Y; Li, N; Wang, S L; Song, Y W; Liu, Y P; Liu, W Y; Ren, H; Zhang, T; Wang, J Y; Chen, X S; Fang, H; Wang, W H; Li, Y X; Jin, J

2018-02-06

This phase I/II clinical trial investigated S-1 administered with intensity-modulated radiotherapy (IMRT) as adjuvant therapy for node-positive gastric cancer. Patients had undergone radical resection and D1/D2 lymph node dissection. In phase I, patients received adjuvant chemoradiotherapy of IMRT (45 Gy in 25 fractions) with concurrent S-1 administered on a dose-escalation schedule to determine the recommended dose (RD). In phase II, the safety and efficacy of the RD of S-1 combined with IMRT were assessed. We consecutively enrolled 73 patients (56 men; median age, 53 years; range, 29-73 years) and the phase I portion of the study included 27 patients. The RD of S-1 administered concomitantly with IMRT was 80 mg m -2  day -1 orally, twice daily. The phase II analysis included 52 patients (46 new patients plus 6 from phase I). 8 patients (15.4%) developed grade 3 or 4 toxicities. There were 21 recurrence events and 15 deaths (1 bowel obstruction, 14 gastric cancer). Three-year disease-free survival and overall survival were 62.2% (95% confidence interval (CI), 48.5-75.9) and 70.0% (95% CI, 56.3-83.7), respectively. The median time to recurrence was 17.5 months (range, 3.8-42.0). The median time from recurrence to death was 7.0 months (range, 1.5-28.7). S-1 combined with IMRT adjuvant chemoradiotherapy is safe and efficacious for advanced gastric cancer.

Planning magnetic resonance imaging for prostate cancer intensity-modulated radiation therapy: Impact on target volumes, radiotherapy dose and androgen deprivation administration.

PubMed

Horsley, Patrick J; Aherne, Noel J; Edwards, Grace V; Benjamin, Linus C; Wilcox, Shea W; McLachlan, Craig S; Assareh, Hassan; Welshman, Richard; McKay, Michael J; Shakespeare, Thomas P

2015-03-01

Magnetic resonance imaging (MRI) scans are increasingly utilized for radiotherapy planning to contour the primary tumors of patients undergoing intensity-modulated radiation therapy (IMRT). These scans may also demonstrate cancer extent and may affect the treatment plan. We assessed the impact of planning MRI detection of extracapsular extension, seminal vesicle invasion, or adjacent organ invasion on the staging, target volume delineation, doses, and hormonal therapy of patients with prostate cancer undergoing IMRT. The records of 509 consecutive patients with planning MRI scans being treated with IMRT for prostate cancer between January 2010 and July 2012 were retrospectively reviewed. Tumor staging and treatment plans before and after MRI were compared. Of the 509 patients, 103 (20%) were upstaged and 44 (9%) were migrated to a higher risk category as a result of findings at MRI. In 94 of 509 patients (18%), the MRI findings altered management. Ninety-four of 509 patients (18%) had a change to their clinical target volume (CTV) or treatment technique, and in 41 of 509 patients (8%) the duration of hormone therapy was changed because of MRI findings. The use of radiotherapy planning MRI altered CTV design, dose and/or duration of androgen deprivation in 18% of patients in this large, single institution series of men planned for dose-escalated prostate IMRT. This has substantial implications for radiotherapy target volumes and doses, as well as duration of androgen deprivation. Further research is required to investigate whether newer MRI techniques can simultaneously fulfill staging and radiotherapy contouring roles. © 2014 Wiley Publishing Asia Pty Ltd.

Inverse planning in three-dimensional conformal and intensity-modulated radiotherapy of mid-thoracic oesophageal cancer.

PubMed

Wu, V W C; Sham, J S T; Kwong, D L W

2004-07-01

The aim of this study is to demonstrate the use of inverse planning in three-dimensional conformal radiation therapy (3DCRT) of oesophageal cancer patients and to evaluate its dosimetric results by comparing them with forward planning of 3DCRT and inverse planning of intensity-modulated radiotherapy (IMRT). For each of the 15 oesophageal cancer patients in this study, the forward 3DCRT, inverse 3DCRT and inverse IMRT plans were produced using the FOCUS treatment planning system. The dosimetric results and the planner's time associated with each of the treatment plans were recorded for comparison. The inverse 3DCRT plans showed similar dosimetric results to the forward plans in the planning target volume (PTV) and organs at risk (OARs). However, they were inferior to that of the IMRT plans in terms of tumour control probability and target dose conformity. Furthermore, the inverse 3DCRT plans were less effective in reducing the percentage lung volume receiving a dose below 25 Gy when compared with the IMRT plans. The inverse 3DCRT plans delivered a similar heart dose as in the forward plans, but higher dose than the IMRT plans. The inverse 3DCRT plans significantly reduced the operator's time by 2.5 fold relative to the forward plans. In conclusion, inverse planning for 3DCRT is a reasonable alternative to the forward planning for oesophageal cancer patients with reduction of the operator's time. However, IMRT has the better potential to allow further dose escalation and improvement of tumour control.

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Xuanfeng; Dionisi, Francesco; Tang, Shikui

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as wellmore » as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.« less

Prostate Cancer Radiation Therapy: What Do Clinicians Have to Know?

PubMed Central

Van Limbergen, Evert J.; van Lin, Emile N.; van Roermund, Joep G. H.; Lambin, Philippe

2016-01-01

Radiotherapy (RT) for prostate cancer (PC) has steadily evolved over the last decades, with improving biochemical disease-free survival. Recently population based research also revealed an association between overall survival and doses ≥ 75.6 Gray (Gy) in men with intermediate- and high-risk PC. Examples of improved RT techniques are image-guided RT, intensity-modulated RT, volumetric modulated arc therapy, and stereotactic ablative body RT, which could facilitate further dose escalation. Brachytherapy is an internal form of RT that also developed substantially. New devices such as rectum spacers and balloons have been developed to spare rectal structures. Newer techniques like protons and carbon ions have the intrinsic characteristics maximising the dose on the tumour while minimising the effect on the surrounding healthy tissue, but clinical data are needed for confirmation in randomised phase III trials. Furthermore, it provides an overview of an important discussion issue in PC treatment between urologists and radiation oncologists: the comparison between radical prostatectomy and RT. Current literature reveals that all possible treatment modalities have the same cure rate, but a different toxicity pattern. We recommend proposing the possible different treatment modalities with their own advantages and side-effects to the individual patient. Clinicians and patients should make treatment decisions together (shared decision-making) while using patient decision aids. PMID:28116302

Using individual patient anatomy to predict protocol compliance for prostate intensity-modulated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caine, Hannah; Whalley, Deborah; Kneebone, Andrew

If a prostate intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) plan has protocol violations, it is often a challenge knowing whether this is due to unfavorable anatomy or suboptimal planning. This study aimed to create a model to predict protocol violations based on patient anatomical variables and their potential relationship to target and organ at risk (OAR) end points in the setting of definitive, dose-escalated IMRT/VMAT prostate planning. Radiotherapy plans from 200 consecutive patients treated with definitive radiation for prostate cancer using IMRT or VMAT were analyzed. The first 100 patient plans (hypothesis-generating cohort) were examined to identifymore » anatomical variables that predict for dosimetric outcome, in particular OAR end points. Variables that scored significance were further assessed for their ability to predict protocol violations using a Classification and Regression Tree (CART) analysis. These results were then validated in a second group of 100 patients (validation cohort). In the initial analysis of the hypothesis-generating cohort, percentage of rectum overlap in the planning target volume (PTV) (%OR) and percentage of bladder overlap in the PTV (%OB) were highlighted as significant predictors of rectal and bladder dosimetry. Lymph node treatment was also significant for bladder outcomes. For the validation cohort, CART analysis showed that %OR of < 6%, 6% to 9% and > 9% predicted a 13%, 63%, and 100% rate of rectal protocol violations respectively. For the bladder, %OB of < 9% vs > 9% is associated with 13% vs 88% rate of bladder constraint violations when lymph nodes were not treated. If nodal irradiation was delivered, plans with a %OB of < 9% had a 59% risk of violations. Percentage of rectum and bladder within the PTV can be used to identify individual plan potential to achieve dose-volume histogram (DVH) constraints. A model based on these factors could be used to reduce planning time, improve work flow, and strengthen plan quality and consistency.« less

A value framework in head and neck cancer care.

PubMed

de Souza, Jonas A; Seiwert, Tanguy Y

2014-01-01

The care of head and neck squamous cell carcinoma has greatly evolved over the past 30 years. From single modality to a multidisciplinary care, there has also been a concurrent increase in treatment intensity, resulting, at many times, in more zealous regimens that patients must endure. In this article, we apply Porter's value model as a framework to balance survival, toxicities, cost, and trade-offs from a patient's perspective in head and neck cancer. This model defines value as the health outcome per dollar achieved. Domains and outcomes that are important to patients, including not only survival or short-term quality of life, but also functional outcomes, recovery, sustainability of recovery, and the lasting consequences of therapy are included in this framework. Other outcomes that are seldom measured in head and neck cancer, such as work disability and financial toxicities, are also included and further discussed. Within this value model and based on evidence, we further discuss de-escalation of care, intensity-modulated radiation therapy, newer surgical methods, and enhancements in the process of care as potential approaches to add value for patients. Finally, we argue that knowing the patient's preferences is essential in the value discussion, as the attribute that will ultimately provide the most value to the individual patient with head and neck cancer.

Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without (18)F-choline PET-CT detected simultaneous integrated boost.

PubMed

Pinkawa, Michael; Piroth, Marc D; Holy, Richard; Klotz, Jens; Djukic, Victoria; Corral, Nuria Escobar; Caffaro, Mariana; Winz, Oliver H; Krohn, Thomas; Mottaghy, Felix M; Eble, Michael J

2012-01-30

In comparison to the conventional whole-prostate dose escalation, an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity. Quality of life after radiotherapy (RT) with vs. without (18)F-choline PET-CT detected simultaneous integrated boost (SIB) was prospectively evaluated in this study. Whole body image acquisition in supine patient position followed 1 h after injection of 178-355MBq (18)F-choline. SIB was defined by a tumor-to-background uptake value ratio > 2 (GTV(PET)). A dose of 76Gy was prescribed to the prostate (PTV(prostate)) in 2Gy fractions, with or without SIB up to 80Gy. Patients treated with (n = 46) vs. without (n = 21) SIB were surveyed prospectively before (A), at the last day of RT (B) and a median time of two (C) and 19 month (D) after RT to compare QoL changes applying a validated questionnaire (EPIC - expanded prostate cancer index composite). With a median cut-off standard uptake value (SUV) of 3, a median GTV(PET) of 4.0 cm(3) and PTV(boost) (GTV(PET) with margins) of 17.3 cm(3) was defined. No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B, C and D (mean differences ≤3 points for all comparisons). Significantly decreasing acute urinary and bowel score changes (mean changes > 5 points in comparison to baseline level at time A) were found for patients with and without SIB. However, long-term urinary and bowel QoL (time D) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups (median changes = 0 points). Only sexual function scores decreased significantly (> 5 points) at time D. Treatment planning with (18)F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity.

An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence

PubMed Central

Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida

2016-01-01

Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides. PMID:27818644

75 FR 73104 - Clinical Development Programs for Sedation Products; Request for Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-29

... sedation claims? Would dose-escalation comparative trial designs be useful in studying sedation products? 5... understanding the physiology of sedation and clinical trial design issues related to the development of sedation... to procedural and intensive care unit (ICU) sedation, as well as associated clinical trial design...

Internationalizing Higher Education in Malaysia: Government Policies and University's Response

ERIC Educational Resources Information Center

Tham, Siew Yean

2013-01-01

The intensity of internationalization has increased with an escalation in internationalization activities, leading to increasing student, program, and institutional mobility. In Malaysia, the internationalization of higher education in terms of student mobility has changed tremendously in the last two decades as the country has shifted from a…

Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate.

PubMed

Myers, Michael A; Hagan, Michael P; Todor, Dorin; Gilbert, Lynn; Mukhopadhyay, Nitai; Randolf, Jessica; Heimiller, Jeffrey; Anscher, Mitchell S

2012-01-01

A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant. From 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy. Patients received 50.4Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128Gy (α/β=3). Patients whose pretreatment PSA was ≥10ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation. Median followup was 53 months (9-68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities. Single-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PubMed

Eisbruch, A; Dawson, L A; Kim, H M; Bradford, C R; Terrell, J E; Chepeha, D B; Teknos, T N; Anzai, Y; Marsh, L H; Martel, M K; Ten Haken, R K; Wolf, G T; Ship, J A

1999-01-01

To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

Patterns of Recurrence in Electively Irradiated Lymph Node Regions After Definitive Accelerated Intensity Modulated Radiation Therapy for Head and Neck Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosch, Sven van den, E-mail: sven.vandenbosch@radboudumc.nl; Dijkema, Tim; Verhoef, Lia C.G.

Purpose: To provide a comprehensive risk assessment on the patterns of recurrence in electively irradiated lymph node regions after definitive radiation therapy for head and neck cancer. Methods and Materials: Two hundred sixty-four patients with stage cT2-4N0-2M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx treated with accelerated intensity modulated radiation therapy between 2008 and 2012 were included. On the radiation therapy planning computed tomography (CT) scans from all patients, 1166 lymph nodes (short-axis diameter ≥5 mm) localized in the elective volume were identified and delineated. The exact sites of regional recurrences were reconstructed and projected on the initial radiationmore » therapy planning CT scan by performing coregistration with diagnostic imaging of the recurrence. Results: The actuarial rate of recurrence in electively irradiated lymph node regions at 2 years was 5.1% (95% confidence interval 2.4%-7.8%). Volumetric analysis showed an increased risk of recurrence with increasing nodal volume. Receiver operating characteristic analysis demonstrated that the summed long- and short-axis diameter is a good alternative for laborious volume calculations, using ≥17 mm as cut-off (hazard ratio 17.8; 95% confidence interval 5.7-55.1; P<.001). Conclusions: An important risk factor was identified that can help clinicians in the pretreatment risk assessment of borderline-sized lymph nodes. Not overtly pathologic nodes with a summed diameter ≥17 mm may require a higher than elective radiation therapy dose. For low-risk elective regions (all nodes <17 mm), the safety of dose de-escalation below the traditional 45 to 50 Gy should be investigated.« less

Image-Guided Intensity-Modulated Radiotherapy for Pancreatic Carcinoma

PubMed Central

Fuss, Martin; Wong, Adrian; Fuller, Clifton D.; Salter, Bill J.; Fuss, Cristina; Thomas, Charles R.

2007-01-01

Purpose To present the techniques and preliminary outcomes of ultrasound-based image-guided intensity-modulated radiotherapy (IG-IMRT) for pancreatic cancer. Materials and Methods Retrospective analysis of 41 patients treated between November 2000 and March 2005 with IG-IMRT to mean total doses of 55 Gy (range, 45–64 Gy). We analyzed the clinical feasibility of IG-IMRT, dosimetric parameters, and outcomes, including acute gastrointestinal toxicity (RTOG grading). Survival was assessed for adenocarcinoma (n = 35) and other histologies. Results Mean daily image-guidance corrective shifts were 4.8 ± 4.3 mm, 7.5 ± 7.2 mm, and 4.6 ± 5.9 mm along the x-, y-, and z-axes, respectively (mean 3D correction vector, 11.7 ± 8.4 mm). Acute upper gastrointestinal toxicity was grade 0–1 in 22 patients (53.7%), grade 2 in 16 patients (39%), and grade 3 in 3 patients (7.3%). Lower gastrointestinal toxicity was grade 0–1 in 32 patients (78%), grade 2 in 7 patients (17.1%), and grade 4 in 2 patients (4.9%). Treatment was stopped early in 4 patients following administration of 30 to 54 Gy. Median survival for adenocarcinoma histology was 10.3 months (18.6 months in patients alive at analysis; n = 8) with actuarial 1- and 2-year survivals of 38% and 25%, respectively. Conclusion Daily image-guidance during delivery of IMRT for pancreatic carcinoma is clinically feasible. The data presented support the conclusion that safety margin reduction and moderate dose escalation afforded by implementation of these new radiotherapy technologies yields preliminary outcomes at least comparable with published survival data. PMID:19262697

Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.

Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses ofmore » 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.« less

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poorvu, Philip D.; Sadow, Cheryl A.; Townamchai, Kanokpis

2013-04-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneummore » plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fury, Matthew G.; Department of Medicine, Weill Cornell Medical College, New York, New York; Lee, Nancy Y.

Purpose: Elevated expression of eukaryotic protein synthesis initiation factor 4E (eIF4E) in histologically cancer-free margins of resected head and neck squamous cell carcinomas (HNSCCs) is mediated by mammalian target of rapamycin complex 1 (mTORC1) and has been associated with increased risk of disease recurrence. Preclinically, inhibition of mTORC1 with everolimus sensitizes cancer cells to cisplatin and radiation. Methods and Materials: This was single-institution phase 1 study to establish the maximum tolerated dose of daily everolimus given with fixed dose cisplatin (30 mg/m{sup 2} weekly × 6) and concurrent intensity modulated radiation therapy for patients with locally and/or regionally advanced head-and-neckmore » cancer. The study had a standard 3 + 3 dose-escalation design. Results: Tumor primary sites were oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), and neck node with occult primary (1). In 4 of 4 cases in which resected HNSCC surgical pathology specimens were available for immunohistochemistry, elevated expression of eIF4E was observed in the cancer-free margins. The most common grade ≥3 treatment-related adverse event was lymphopenia (92%), and dose-limiting toxicities (DLTs) were mucositis (n=2) and failure to thrive (n=1). With a median follow up of 19.4 months, 2 patients have experienced recurrent disease. The maximum tolerated dose was everolimus 5 mg/day. Conclusions: Head-and-neck cancer patients tolerated everolimus at therapeutic doses (5 mg/day) given with weekly cisplatin and intensity modulated radiation therapy. The regimen merits further evaluation, especially among patients who are status post resection of HNSCCs that harbor mTORC1-mediated activation of eIF4E in histologically negative surgical margins.« less

Outcomes of induction chemotherapy followed by chemoradiation using intensity-modulated radiation therapy for esophageal adenocarcinoma.

PubMed

Gerber, N; Ilson, D H; Wu, A J; Janjigian, Y Y; Kelsen, D P; Zheng, J; Zhang, Z; Bains, M S; Rizk, N; Rusch, V W; Goodman, K A

2014-04-01

This study looks at toxicity and survival data when chemoradiation (CRT) is delivered using intensity-modulated radiation therapy (IMRT) after induction chemotherapy. Forty-one patients with esophageal adenocarcinoma treated with IMRT from March 2007 to May 2009 at Memorial Sloan-Kettering Cancer Center were analyzed. All patients received induction chemotherapy prior to CRT. Thirty-nine percent (n = 16) of patients underwent surgical resection less than 4 months after completing CRT. Patients were predominantly male (78%), with a median age of 68 years (range 32-85 years). The majority of acute treatment-related toxicity was hematologic or gastrointestinal, with 17% of patients having grade 3+ hematologic toxicity and 12% of patients having grade 3+ gastrointestinal toxicity. Only two patients developed grade 2-3 pneumonitis (5%) and 5 patients experienced post-operative pulmonary complications (29%). Eight patients (20%) required a treatment break. With a median follow up of 41 months for surviving patients, 2-year overall survival was 61%, and the cumulative incidences of local failure (LF) and distant metastases were 40% and 51%, respectively. This rate of LF was reduced to 13% in patients who underwent surgical resection. Surgery and younger age were significant predictors of decreased time to LF on univariate analysis. Induction chemotherapy followed by CRT using IMRT in the treatment of esophageal cancer is well tolerated and is not associated with an elevated risk of postoperative pulmonary complications. The use of IMRT may allow for integration of more intensified systemic therapy or radiation dose escalation for esophageal adenocarcinoma, ultimately improving outcomes for patients with this aggressive disease. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Multimodality treatment with intensity modulated radiation therapy for esophageal cancer.

PubMed

La, T H; Minn, A Y; Su, Z; Fisher, G A; Ford, J M; Kunz, P; Goodman, K A; Koong, A C; Chang, D T

2010-05-01

The objective of this study is to determine the feasibility and report the outcome of patients with locally advanced esophageal cancer treated with preoperative or definitive chemoradiotherapy (CRT) using intensity-modulated radiation therapy (IMRT). Between 2003 and 2007, 30 patients with non-cervical esophageal cancer received concurrent chemotherapy and IMRT at Stanford University. Eighteen patients were planned for definitive CRT and 12 were planned for preoperative CRT. All patients had computed tomography-based treatment planning and received IMRT. The median dose delivered was 50.4 Gy. Patients planned for preoperative CRT underwent surgery 4-13 weeks (median 8.3 weeks) following completion of CRT. Median follow-up of surviving patients from start of RT was 24.2 months (range 8.2-38.3 months). The majority of tumors were adenocarcinomas (67%) and poorly differentiated (57%). Tumor location was 7% upper, 20% mid, 47% lower, and 27% gastroesophageal junction. Actuarial 2-year local-regional control (LRC) was 64%. High tumor grade was an adverse prognostic factor for LRC and overall survival (OS) (P= 0.015 and 0.012, respectively). The 2-year LRC was 83% vs. 51% for patients treated preoperatively vs. definitively (P= 0.32). The 2-year disease-free and OS were 38% and 56%, respectively. Twelve patients (40%) required feeding tube placement, and the average weight loss from baseline was 4.8%. Twelve (40%) patients experienced grade 3+ acute complications and one patient died of complications following feeding tube placement. Three patients (10%) required a treatment break. Eight patients (27%) experienced grade 3 late complications. No grade 4 complications were seen. IMRT was effective and well tolerated. Disease recurrence remains a challenge and further investigation with dose escalation to improve LRC and OS is warranted.

Simultaneous integrated boost to intraprostatic lesions using different energy levels of intensity-modulated radiotherapy and volumetric-arc therapy

PubMed Central

Sonmez, S; Erbay, G; Guler, O C; Arslan, G

2014-01-01

Objective: This study compared the dosimetry of volumetric-arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) with a dynamic multileaf collimator using the Monte Carlo algorithm in the treatment of prostate cancer with and without simultaneous integrated boost (SIB) at different energy levels. Methods: The data of 15 biopsy-proven prostate cancer patients were evaluated. The prescribed dose was 78 Gy to the planning target volume (PTV78) including the prostate and seminal vesicles and 86 Gy (PTV86) in 39 fractions to the intraprostatic lesion, which was delineated by MRI or MR-spectroscopy. Results: PTV dose homogeneity was better for IMRT than VMAT at all energy levels for both PTV78 and PTV86. Lower rectum doses (V30–V50) were significantly higher with SIB compared with PTV78 plans in both IMRT and VMAT plans at all energy levels. The bladder doses at high dose level (V60–V80) were significantly higher in IMRT plans with SIB at all energy levels compared with PTV78 plans, but no significant difference was observed in VMAT plans. VMAT plans resulted in a significant decrease in the mean monitor units (MUs) for 6, 10, and 15 MV energy levels both in plans with and those without SIB. Conclusion: Dose escalation to intraprostatic lesions with 86 Gy is safe without causing serious increase in organs at risk (OARs) doses. VMAT is advantageous in sparing OARs and requiring less MU than IMRT. Advances in knowledge: VMAT with SIB to intraprostatic lesion is a feasible method in treating prostate cancer. Additionally, no dosimetric advantage of higher energy is observed. PMID:24319009

Etiologic theories of idiopathic scoliosis. Somatic nervous system and the NOTOM escalator concept as one component in the pathogenesis of adolescent idiopathic scoliosis.

PubMed

Burwell, R G; Dangerfield, P H; Freeman, B J C

2008-01-01

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). In recent years encouraging advances thought to be related to the pathogenesis of AIS have been made in several fields. After reviewing concepts of AIS pathogenesis we formulated a collective model of pathogenesis. The central concept of this collective model is a normal neuro-osseous timing of maturation (NOTOM) system operating in a child's internal world during growth and maturation; this provides a dynamic physiological balance of postural equilibrium continuously renewed between two synchronous, polarized processes (NOTOM escalator) linked through sensory input and motor output, namely: 1) osseous escalator-increasing skeletal size and relative segmental mass, and 2) neural escalator - including the CNS body schema. The latter is recalibrated continuously as the body adjusts to biomechanical and kinematic changes resulting from skeletal enlargement, enabling it to coordinate motor actions. We suggest that AIS progression results from abnormality of the neural and/or osseous components of these normal escalator in time and/or space - as asynchrony and/or asymmetries - which cause a failure of neural systems to control asymmetric growth of a rapidly enlarging and moving adolescent spine. This putative initiating asymmetric growth in the spine is explained in separate papers as resulting from dysfunction of the hypothalamus expressed through the sympathetic nervous system (leptin-sympathetic nervous system concept for AIS pathogenesis). In girls, the expression of AIS may result from disharmony between the somatic and autonomic nervous systems - relative postural maturational delay in the somatic nervous system and hypothalamic dysfunction in the autonomic nervous system, with the conflict being fought out in the spine and trunk of the girl and compounded by biomechanical spinal growth modulation.

A Unified Electronic Tool for CPR and Emergency Treatment Escalation Plans Improves Communication and Early Collaborative Decision Making for Acute Hospital Admissions.

PubMed

Johnson, Mae; Whyte, Martin; Loveridge, Robert; Yorke, Richard; Naleem, Shairana

2017-01-01

The National Confidential Enquiry into Patient Outcomes and Death (NCEPOD) report 'Time to Intervene' (2012) stated that in a substantial number of cases, resuscitation is attempted when it was thought a 'do not attempt cardiopulmonary resuscitation' (DNACPR) decision should have been in place. Early decisions about CPR status and advance planning about limits of care now form part of national recommendations by the UK Resuscitation Council (2016). Treatment escalation plans (TEP) document what level of treatment intervention would be appropriate if a patient were to become acutely unwell and were not previously formally in place at King's College Hospital. A unifying paper based form was successfully piloted in the Acute Medical Unit, introducing the TEP and bringing together decision making around both treatment escalation and CPR status. Subsequently an electronic order-set for CPR status and treatment escalation was launched in April 2015 which led to a highly visible CPR and escalation status banner on the main screen at the top of the patient's electronic record. Ultimately due to further iterations in the electronic process by December 2016, all escalation decisions for acutely admitted patients now have high quality supporting, explanatory documentation with 100% having TEPs in place. There is now widespread multidisciplinary engagement in the process of defining limits of care for acutely admitted medical patients within the first 14 hours of admission and a strategy for rolling this process out across all the divisions of the hospital through our Deteriorating Patient Group (DPG). The collaborative design with acute medical, palliative and intensive care teams and the high visibility provided by the electronic process in the Electronic Patient Record (EPR) has enhanced communication with these teams, patients, nursing staff and the multidisciplinary team by ensuring clarity through a universally understood process about escalation and CPR. Clarity and openness about these discussions have been welcomed by patient focus groups facilitated via our acute medicine patient experience committee. There has been a shift in medical culture where transparency about limits of care has contributed to improving patient safety and quality of care through reducing unnecessary CPR supported by focus groups of staff.

Using a Context-aware Medical Application to Address Information Needs for Extubation Decisions

PubMed Central

Zhu, Xinxin; Lord, William

2005-01-01

Information overload has been one of the causes of preventable medical errors [1] and escalating costs [2]. A context-aware application with embedded clinical knowledge is proposed to provide practitioners with the appropriate amount of information and content. We developed a prototype of a context-aware medical application to address clinicians’ information needs that arise in a data-intensive unit, the Cardio-Thoracic Intensive Care Unit (CTICU). A major clinical decision supported by the prototype, the extubation decision, is illustrated. PMID:16779455

Combination of intrathecal opioids with bupivacaine attenuates opioid dose escalation in chronic noncancer pain patients.

PubMed

Veizi, I Elias; Hayek, Salim M; Narouze, Samer; Pope, Jason E; Mekhail, Nagy

2011-10-01

The purpose of this study was to examine the effect of intrathecal (IT) coadministration of bupivacaine with opioids during the initial phase of opioid titration and up to 1 year after implantation of an IT drug delivery system (IDDS). The study was designed as a retrospective study. OUTCOMES ANALYZED: The outcomes analyzed for this study were pain relief, oral opioid consumption, IT opioid, and bupivacaine dosage. METHODS AND PATIENT POPULATION: The patient population for this study were consecutively implanted patients over a period of 6 years in a tertiary single center with multiple practitioners. In this retrospective study, 126 consecutive noncancer intractable pain patients were implanted with IDDS and initiated with an IT opioid (O) as a single medication or an IT opioid and bupivacaine (O + B). Pain intensity, amount of oral opioids, dose, rate, and concentration of IT opioids and bupivacaine, and number and type of IT medication used were recorded at preimplant, implant, and at 3, 6, and 12 months postimplant. The intervention used for the study was the IT delivery device implant. Significant reduction in pain intensity was observed in both groups at 12 months postimplant (O group: baseline 7.42 ± 2.1 to 5.85 ± 2.8 [n = 72, P < 0.001]; O + B group 7.35 ± 2 to 5.03 ± 2.4 (n = 54; P < 0.001]). The combination of opioids with bupivacaine from the start of IT infusion treatment resulted in a reduced progression of opioid dose escalation in comparison to patients started with opioids (O group). The rate of increase of IT opioids in the O group at 12 months was 535 ± 180%, whereas in the O + B, the dose increase was significantly lower at 185 ± 85% (P < 0.004). In both groups, there was a statistically significant decrease in oral opioid consumption compared with preimplant doses. Concomitant initial coadministration of IT bupivacaine with opioids blunts the rate of IT opioid dose escalation during the first year after implant of an IDDS. More studies are necessary to thoroughly examine IT opioid dose escalation and the effects of addition of bupivacaine to IT opioids. Blunting IT opioid dose escalation may be a beneficial long-term effect of IT bupivacaine. Wiley Periodicals, Inc.

Escalated cocaine "binges" in rats: enduring effects of social defeat stress or intra-VTA CRF.

PubMed

Leonard, Michael Z; DeBold, Joseph F; Miczek, Klaus A

2017-09-01

Exposure to intermittent social defeat stress elicits corticotropin releasing factor (CRF) release into the VTA and induces long-term modulation of mesocorticolimbic dopamine activity in rats. These adaptations are associated with an intense cocaine-taking phenotype, which is prevented by CRF receptor antagonists. The present studies examine whether infusion of CRF into the VTA is sufficient to escalate cocaine-taking behavior, in the absence of social defeat experience. Additionally, we aimed to characterize changes in cocaine valuation that may promote binge-like cocaine intake. Male Long-Evans rats were microinjected into the VTA with CRF (50 or 500 ng/side), vehicle, or subjected to social defeat stress, intermittently over 10 days. Animals were then trained to self-administer IV cocaine (FR5). Economic demand for cocaine was evaluated using a within-session behavioral-economics threshold procedure, which was followed by a 24-h extended access "binge." Rats that experienced social defeat or received intra-VTA CRF microinfusions (50 ng) both took significantly more cocaine than controls over the 24-h binge but showed distinct patterns of intake. Behavioral economic analysis revealed that individual demand for cocaine strongly predicts binge-like consumption, and demand elasticity (i.e. α) is augmented by intra-VTA CRF, but not by social defeat. The effects of CRF on cocaine-taking were also prevented by intra-VTA pretreatment with CP376395, but not Astressin-2B. Repeated infusion of CRF into the VTA persistently alters cocaine valuation and intensifies binge-like drug intake in a CRF-R1-dependent manner. Conversely, the persistent pattern of cocaine bingeing induced by social defeat stress may suggest impaired inhibitory control, independent of reward valuation.

From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer.

PubMed

Leonardi, Maria Cristina; Ricotti, Rosalinda; Dicuonzo, Samantha; Cattani, Federica; Morra, Anna; Dell'Acqua, Veronica; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

2016-10-01

Radiotherapy improves local control in breast cancer (BC) patients which increases overall survival in the long term. Improvements in treatment planning and delivery and a greater understanding of BC behaviour have laid the groundwork for high-precision radiotherapy, which is bound to further improve the therapeutic index. Precise identification of target volumes, better coverage and dose homogeneity have had a positive impact on toxicity and local control. The conformity of treatment dose due to three-dimensional radiotherapy and new techniques such as intensity modulated radiotherapy makes it possible to spare surrounding normal tissue. The widespread use of dose-volume constraints and histograms have increased awareness of toxicity. Real time image guidance has improved geometric precision and accuracy, together with the implementation of quality assurance programs. Advances in the precision of radiotherapy is also based on the choice of the appropriate fractionation and approach. Adaptive radiotherapy is not only a technical concept, but is also a biological concept based on the knowledge that different types of BC have distinctive patterns of locoregional spread. A greater understanding of cancer biology helps in choosing the treatment best suited to a particular situation. Biomarkers predictive of response play a crucial role. The combination of radiotherapy with molecular targeted therapies may enhance radiosensitivity, thus increasing the cytotoxic effects and improving treatment response. The appropriateness of an alternative fractionation, partial breast irradiation, dose escalating/de-escalating approaches, the extent of nodal irradiation have been examined for all the BC subtypes. The broadened concept of adaptive radiotherapy is vital to high-precision treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An

2007-03-15

Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribsmore » and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, Reid F.; Zhai, Huifang; Both, Stefan

Purpose: Uncontrolled local growth is the cause of death in ∼30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. Methods: The authors compared DS, PBS, andmore » IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. Results: Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6–53.8 and 34.9–52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. Conclusions: Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.« less

Implementation and Evaluation of a Ward-Based eLearning Program for Trauma Patient Management.

PubMed

Curtis, Kate; Wiseman, Taneal; Kennedy, Belinda; Kourouche, Sarah; Goldsmith, Helen

2016-01-01

The majority of trauma nursing education is focused on the emergency phases of care. We describe the development and evaluation of a trauma eLearning module for the ward environment. The module was developed using adult learning principles and implemented in 2 surgical wards. There were 3 phases of evaluation: (1) self-efficacy of nurses; (2) relevance and usability of the module and; (3) application of knowledge learnt. The majority indicated they had applied new knowledge, particularly when performing a physical assessment (85.7%), communicating (91.4%), and identifying risk of serious illness (90.4%). Self-efficacy relating to confidence in caring for patients, communication, and escalating clinical deterioration improved (p = .023). An eLearning trauma patient assessment module for ward nursing staff improves nursing knowledge and self-efficacy.

Educating Mental Health Clinicians About Sensory Modulation to Enhance Clinical Practice in a Youth Acute Inpatient Mental Health Unit: A Feasibility Study.

PubMed

Blackburn, Julie; McKenna, Brian; Jackson, Brian; Hitch, Danielle; Benitez, Jessica; McLennan, Cathy; Furness, Trentham

2016-07-01

There is an emergence of literature describing effective sensory modulation (SM) interventions to de-escalate violence and aggression among mental health inpatients. However, the evidence is limited to adult settings, with the effect of SM in youth acute settings unknown. Yet, before SM may be used as a de-escalation intervention in youth acute settings, multidisciplinary staff need to be educated about and supported in the clinical application of SM. In the current study, an online SM education package was developed to assist mental health staff understand SM. This was blended with action learning sets (ALS), small group experiential opportunities consisting staff and consumers to learn about SM resources, and the support of SM trained nurses. The aims of the study were to evaluate the effectiveness of this SM education intervention in (a) transferring knowledge of SM to staff, and (b) translating this knowledge into practice in a youth acute inpatient mental health unit. A mixed methods research design with an 11-item pre- and post-education questionnaire was used along with three-month follow-up focus groups. The SM education improved understanding about SM (all 11-items p ≤ 0.004, r ≥ 0.47). Three-months after SM education, four themes evident in the focus group data emerged about the practice and process of SM; (1) translating of learning into practice, (2) SM in practice, (3) perceptions of SM benefits, and (4) limitations of SM. A blended SM education process enhanced clinical practice in the unit, yet participants were mindful of limitations of SM in situations of distress or escalating agitation.

Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives

PubMed Central

Serrano, Nicholas A; Kalman, Noah S; Anscher, Mitchell S

2017-01-01

Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity. PMID:28814898

A Tale of Two Diets: What Can We Learn from the Diet Wars?

ERIC Educational Resources Information Center

Larsen, Dawn; Murray-Davis, Margaret

2005-01-01

During the last two decades, obesity rates in the United States have escalated dramatically, and intense media coverage of obesity issues has fueled consumer interest in low-carbohydrate diets designed to promote rapid weight loss. The food industry has fostered the assumption that a drop in carbohydrate consumption will translate into a drop in…

Long-term effects of forest herbicides on plant diversity in pine plantations in the southeast

Treesearch

James H. Miller

2001-01-01

Conservation of biological diversity is an important issue on public and private forests worldwide. As concern for diversity maintenance escalates, more pressure will be placed on the forestry community to understand the efjfects of silvicultural treatments on biodiversity and its sustainable management Biodiversity conservation in intensively managed forested regions...

Behavioral and Pharmacogenetics of Aggressive Behavior

PubMed Central

Takahashi, Aki; Quadros, Isabel M.; de Almeida, Rosa M. M.; Miczek, Klaus A.

2013-01-01

Serotonin (5-HT) has long been considered as a key transmitter in the neurocircuitry controlling aggression. Impaired regulation of each subtype of 5-HT receptor, 5-HT transporter, synthetic and metabolic enzymes has been linked particularly to impulsive aggression. The current summary focuses mostly on recent findings from pharmacological and genetic studies. The pharmacological treatments and genetic manipulations or polymorphisms of a specific target (e.g., 5-HT1A receptor) can often result in inconsistent results on aggression, due to “phasic” effects of pharmacological agents vs “trait”-like effects of genetic manipulations. Also, the local administration of a drug using the intracranial microinjection technique has shown that activation of specific subtypes of 5-HT receptors (5-HT1A and 5-HT1B) in mesocorticolimbic areas can reduce species-typical and other aggressive behaviors, but the same receptors in the medial prefrontal cortex or septal area promote escalated forms of aggression. Thus, there are receptor populations in specific brain regions that preferentially modulate specific types of aggression. Genetic studies have shown important gene × environment interactions; it is likely that the polymorphisms in the genes of 5-HT transporters (e.g., MAO A) or rate-limiting synthetic and metabolic enzymes of 5-HT determine the vulnerability to adverse environmental factors that escalate aggression. We also discuss the interaction between the 5-HT system and other systems. Modulation of 5-HT neurons in the dorsal raphe nucleus by GABA, glutamate, and CRF profoundly regulate aggressive behaviors. Also, interactions of the 5-HT system with other neuropeptides (arginine vasopressin, oxytocin, neuropeptide Y, opioid) have emerged as important neurobiological determinants of aggression. Studies of aggression in genetically modified mice identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or indirectly (e.g. BDNF, nNOS, αCaMKII, Neuropeptide Y). The future agenda delineates specific receptor subpopulations for GABA, glutamate and neuropeptides as they modulate the canonical aminergic neurotransmitters in brainstem, limbic and cortical regions with the ultimate outcome of attenuating or escalating aggressive behavior. PMID:22297576

Flu, risks, and videotape: escalating fear and avoidance.

PubMed

Rosoff, Heather; John, Richard S; Prager, Fynnwin

2012-04-01

While extensive risk perception research has focused on emotions, cognitions, and behavior at static points in time, less attention has been paid to how these variables might change over time. This study assesses how negative affect, threat beliefs, perceived risk, and intended avoidance behavior change over the course of an escalating biological disaster. A scenario simulation methodology was used that presents respondents with a video simulation of a 15-day series of local news reports to immerse respondents in the developing details of the disaster. Systemic manipulation of the virus's causal origin (terrorist attack, medical lab accident, unknown) and the respondent's proximity to the virus (local vs. opposite coast) allowed us to investigate the dynamics of public response. The unfolding scenario was presented in discrete episodes, allowing responses to be tracked over the episodes. The sample includes 600 respondents equally split by sex and by location, with half in the Washington, DC area, and half in the Los Angeles area. The results showed respondents' reactions to the flu epidemic increased as the disaster escalated. More importantly, there was considerable consistency across respondents' emotional, cognitive, and behavioral responses to the epidemic over the episodes. In addition, the reactions of respondents proximally closer to the epidemic increased more rapidly and with greater intensity than their distant counterparts. Finally, as the flu epidemic escalated, both terrorist and accidental flu releases were perceived as being less risky and were less likely to lead to avoidance behavior compared to the unknown flu release. © 2012 Society for Risk Analysis.

Enhanced methane production from pig slurry with pulsed electric field pre-treatment.

PubMed

Safavi, Seyedeh Masoumeh; Unnthorsson, Runar

2018-02-01

Intensive amount of manure produced in pig breeding sectors represents negative impact on the environment and requires optimal management. Anaerobic digestion as a well-known manure management process was optimized in this experimental study by pulsed electric field (PEF) pre-treatment. The effect of PEF on methane production was investigated at three different intensities (15, 30 and 50 kWh/m 3 ). The results indicate that the methane production and chemical oxygen demand (COD) removal was improved by continuous escalation of applied intensity, up to 50 kWh/m 3 . In comparison with untreated slurry, methane production and COD removal were increased up to 58% and 44%, respectively.

Fire effects on aquatic ecosystems: An assessment of the current state of the science

Treesearch

Rebecca J. Bixby; Scott D. Cooper; Robert E. Gresswell; Lee E. Brown; Clifford N. Dahm; Kathleen A. Dwire

2015-01-01

Fire is a prevalent feature of many landscapes and has numerous and complex effects on geological, hydrological, ecological, and economic systems. In some regions, the frequency and intensity of wildfire have increased in recent years and are projected to escalate with predicted climatic and landuse changes. In addition, prescribed burns continue to be used in many...

Influence of land management and hydrology on urea fate and transport within a Coastal Plain watershed dominated by intensive poultry agriculture

USDA-ARS?s Scientific Manuscript database

Increasing nutrient loads delivered from the landscape to coastal ecosystems has widely been recognized as a major contributor to coastal eutrophication and as a driver of the escalation of harmful algal blooms (HABs). Urea, a form of organic nitrogen, is a common nutrient found in fertilizers, manu...

Interhospital transfer of children in respiratory failure: a clinician interview qualitative study.

PubMed

Odetola, Folafoluwa O; Anspach, Renee R; Han, Yong Y; Clark, Sarah J

2017-02-01

To investigate the decision making underlying transfer of children with respiratory failure from level II to level I pediatric intensive care unit care. Interviews with 19 eligible level II pediatric intensive care unit physicians about a hypothetical scenario of a 2-year-old girl in respiratory failure: RESULTS: At baseline, indices critical to management were as follows: OI (53%), partial pressure of oxygen in arterial blood (Pao 2 )/Fio 2 (32%), and inflation pressure (16%). Poor clinical response was signified by high OI, inflation pressure, and Fio 2 , and low Pao 2 /Fio 2 . At EP 1, 18 of 19 respondents would initiate high-frequency oscillatory ventilation, and 1 would transfer. At EP 2, 15 of 18 respondents would maintain high-frequency oscillatory ventilation, 9 of them calling to discuss transfer. All respondents would transfer if escalated therapies failed to reverse the patient's clinical deterioration. Interhospital transfer of children in respiratory failure is triggered by poor response to escalation of locally available care modalities. This finding provides new insight into decision making underlying interhospital transfer of children with respiratory failure. Copyright © 2016 Elsevier Inc. All rights reserved.

The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial.

PubMed

Sultanem, Khalil; Patrocinio, Horacio; Lambert, Christine; Corns, Robert; Leblanc, Richard; Parker, William; Shenouda, George; Souhami, Luis

2004-01-01

Despite major advances in treatment modalities, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. Exploring hypofractionated regimens to replace the standard 6-week radiotherapy schedule is an attractive strategy as an attempt to prevent accelerated tumor cell repopulation. There is equally interest in dose escalation to the gross tumor volume where the majority of failures occur. We report our preliminary results using hypofractionated intensity-modulated accelerated radiotherapy regimen in the treatment of patients with GBM. Between July 1998 and December 2001, 25 patients with histologically proven diagnosis of GBM, Karnofsky performance status > or =60, and a postoperative tumor volume < or =110 cm3 were treated with a hypofractionated accelerated course of radiotherapy. The gross tumor volume (GTV) was defined as the contrast-enhancing lesion on the postoperative MRI T1-weighted images with the latter fused with computed tomography images for treatment planning. The planning target volume was defined as GTV + 1.5-cm margin. Using forward-planning intensity modulation (step-and-shoot technique), 60 Gy in 20 daily fractions of 3 Gy each were given to the GTV, whereas the planning target volume received a minimum of 40 Gy in 20 fractions of 2 Gy each at its periphery. Treatments were delivered over a 4-week period using 5 daily fractions per week. Dose was prescribed at the isocenter (ICRU point). Three beam angles were used in all of the cases. Treatments were well tolerated. Acute toxicity was limited to increased brain edema during radiotherapy in 2 patients who were on tapering doses of corticosteroids. This was corrected by increasing the steroid dose. At a median follow-up of 8.8 months, no late toxicity was observed. One patient experienced visual loss at 9 months after completion of treatment. MRI suggested nonspecific changes to the optic chiasm. On review of the treatment plan, the total dose to the optic chiasm was confirmed to be equal to or less than 40 Gy in 20 fractions. When Radiation Therapy Oncology Group recursive partitioning analysis was used, 10 patients were class III-IV, and 15 patients were class V-VI. To date, 21 patients have had clinical and/or radiologic evidence of disease progression, and 16 patients have died. The median survival was 9.5 months (range: 2.8-22.9 months), the 1-year survival rate was 40%, and the median progression-free survival was 5.2 months (range: 1.9-12.8 months). This hypofractionated accelerated irradiation schedule using forward planning (step-and-shoot) hypofractionated, intensity-modulated accelerated radiotherapy is feasible and seems to be a safe treatment for patients with GBM. A 2-week reduction in the treatment time may be of valuable benefit for this group of patients. However, despite this accelerated regimen, no survival advantage has been observed.

Effects of Gabra2 Point Mutations on Alcohol Intake: Increased Binge-Like and Blunted Chronic Drinking by Mice.

PubMed

Newman, Emily L; Gunner, Georgia; Huynh, Polly; Gachette, Darrel; Moss, Stephen J; Smart, Trevor G; Rudolph, Uwe; DeBold, Joseph F; Miczek, Klaus A

2016-11-01

Alcohol use disorders are associated with single-nucleotide polymorphisms in GABRA2, the gene encoding the GABA A receptor α2-subunit in humans. Deficient GABAergic functioning is linked to impulse control disorders, intermittent explosive disorder, and to drug abuse and dependence, yet it remains unclear whether α2-containing GABA A receptor sensitivity to endogenous ligands is involved in excessive alcohol drinking. Male wild-type (Wt) C57BL/6J and point-mutated mice rendered insensitive to GABAergic modulation by benzodiazepines (BZD; H101R), allopregnanolone (ALLO) or tetrahydrodeoxycorticosterone (THDOC; Q241M), or high concentrations of ethanol (EtOH) (S270H/L277A) at α2-containing GABA A receptors were assessed for their binge-like, moderate, or escalated chronic drinking using drinking in the dark, continuous access (CA) and intermittent access (IA) to alcohol protocols, respectively. Social approach by mutant and Wt mice in forced alcohol abstinence was compared to approach by EtOH-naïve controls. Social deficits in forced abstinence were treated with allopregnanolone (0, 3.0, 10.0 mg/kg, intraperitoneal [i.p.]) or midazolam (0, 0.56, 1.0 mg/kg, i.p.). Mice with BZD-insensitive α2-containing GABA A receptors (H101R) escalated their binge-like drinking. Mutants harboring the Q241M point substitution in Gabra2 showed blunted chronic intake in the CA and IA protocols. S270H/L277A mutants consumed excessive amounts of alcohol but, unlike wild-types, they did not show forced abstinence-induced social deficits. These findings suggest a role for: (i) H101 in species-typical binge-like drinking, (ii) Q241 in escalated chronic drinking, and (iii) S270 and/or L277 in the development of forced abstinence-associated social deficits. Clinical findings report reduced BZD-binding sites in the cortex of dependent patients; the present findings suggest a specific role for BZD-sensitive α2-containing receptors. In addition, amino acid residue 241 in Gabra2 is necessary for positive modulation and activation of GABA A receptors by ALLO and THDOC; we postulate that neurosteroid action on α2-containing receptor may be necessary for escalated chronic EtOH intake. Copyright © 2016 by the Research Society on Alcoholism.

Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects.

PubMed

Scherz, Michael W; Brossard, Patrick; D'Ambrosio, Daniele; Ipek, Murat; Dingemanse, Jasper

2015-06-01

Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent reduction of circulating lymphocytes upon oral dosing. Previous studies showed that single doses up to 75 mg or multiple doses up to 40 mg once daily are well tolerated, and heart rate (HR) reduction and atrio-ventricular conduction delays upon treatment initiation are reduced by gradual up-titration to the maintenance dose. This single-center, open-label, randomized, multiple-dose, 3-treatment, 3-way crossover study compared the tolerability, safety, pharmacokinetics, cardiodynamics, and effects on lymphocytes of 3 different up-titration regimens of ponesimod in healthy male and female subjects. Up-titration regimens comprised escalating periods of b.i.d. dosing (2.5 or 5 mg) and q.d. dosing (10 or 20 mg or both). After the third up-titration period a variable-duration washout period of 1-3 days was followed by re-challenge with a single 20-mg dose of ponesimod. Adverse events were transient and mild to moderate in intensity, not different between regimens. HR decrease after the first dose was greater than after all subsequent doses, including up-titration doses. Little or no HR change was observed with morning doses of b.i.d. regimens, suggesting that 2.5 and 5 mg b.i.d. are sufficient to sustain cardiac desensitization for the 12-hours dosing interval. © 2015, The American College of Clinical Pharmacology.

Effect of a simple dose-escalation schedule on tramadol tolerability : assessment in the clinical setting.

PubMed

Tagarro, I; Herrera, J; Barutell, C; Díez, M C; Marín, M; Samper, D; Busquet, C; Rodríguez, M J

2005-01-01

To assess the effect of a very simple dose-escalation schedule on tramadol tolerability in clinical practice. This schedule consists of starting treatment with sustained-release tramadol 50mg twice daily, and escalating the dose around 7 days later to 100mg twice daily. Data from 1925 outpatients with non-malignant chronic pain were collected in this multicentre, prospective, comparative, non-randomised, open, observational study. A total of 1071 patients (55.6%) were included in the dose-escalation group (50mg group) and 854 patients (44.4%) in the control group (sustained-release tramadol 100mg twice daily; 100mg group). The proportion of patients who interrupted tramadol treatment due to the occurrence of adverse reactions was significantly lower in the 50mg group (5.6%) than in the 100mg group (12.6%) [p = 0.001]. In line with this, the proportion of patients who experienced at least one adverse reaction was significantly lower in the 50mg group (18.4%) than in the 100mg group (30.4%) [p = 0.001] and, interestingly, the two most frequently reported adverse reactions, nausea and dizziness, were found with a significantly lower frequency in the 50mg group (p < 0.001). Multivariate analysis showed that the risk of safety-related treatment cessations was 2.3 times higher in the 100mg group than in the 50mg group, and 2.2 times higher in females than in males. The two treatments were equally effective in reducing pain intensity (p = 0.121), measured as a reduction in pain score obtained by means of a visual analogue scale. The instauration of tramadol treatment, starting with sustained-release 50mg capsules twice daily and escalating the dose some days later to 100mg twice daily, was shown to be an effective and easy way to improve tramadol tolerability in clinical practice, whilst maintaining its analgesic efficacy.

Overview of escalator applications in rail transit

NASA Technical Reports Server (NTRS)

Deshpande, G.; Rubenstein, L.

1980-01-01

The difference in operating environment and in construction between escalators in transit and nontransit use, the impact of recent escalator innovations, and areas which could benefit from urban mass transportation administration sponsored research and development are determined. Several factors causing a more severe transit escalator operating environment are identified. There are no significant design differences between transit and nontransit escalators. Recent innovations that have affected performance and cost include outdoor escalators, extra flat steps at both landings, and modular escalators. Data were collected by interviews at transit agencies. Long term, unscheduled, escalator maintenance records were available for analysis from one property. A description of escalator operating principles is provided. Transit represents less than 5% of the U.S. escalator market. Transit agencies have limited leverage on escalator industry practices. A substantial impact on transit escalator cost and performance can be achieved by research identifying when and how to apply and specify several of the more recent innovations. Purchase of escalators under long term (25 year) maintenance contracts is one method that has been used to promote escalators manufactured for minimum life cycle cost.

Positron Emission Tomography for Pre-Clinical Sub-Volume Dose Escalation

NASA Astrophysics Data System (ADS)

Bass, Christopher Paul

Purpose: This dissertation focuses on establishment of pre-clinical methods facilitating the use of PET imaging for selective sub-volume dose escalation. Specifically the problems addressed are 1.) The difficulties associated with comparing multiple PET images, 2.) The need for further validation of novel PET tracers before their implementation in dose escalation schema and 3.) The lack of concrete pre-clinical data supporting the use of PET images for guidance of selective sub-volume dose escalations. Methods and materials: In order to compare multiple PET images the confounding effects of mispositioning and anatomical change between imaging sessions needed to be alleviated. To mitigate the effects of these sources of error, deformable image registration was employed. A deformable registration algorithm was selected and the registration error was evaluated via the introduction of external fiducials to the tumor. Once a method for image registration was established, a procedure for validating the use of novel PET tracers with FDG was developed. Nude mice were used to perform in-vivo comparisons of the spatial distributions of two PET tracers, FDG and FLT. The spatial distributions were also compared across two separate tumor lines to determine the effects of tumor morphology on spatial distribution. Finally, the research establishes a method for acquiring pre-clinical data supporting the use of PET for image-guidance in selective dose escalation. Nude mice were imaged using only FDG PET/CT and the resulting images were used to plan PET-guided dose escalations to a 5 mm sub-volume within the tumor that contained the highest PET tracer uptake. These plans were then delivered using the Small Animal Radiation Research Platform (SARRP) and the efficacy of the PET-guided plans was observed. Results and Conclusions: The analysis of deformable registration algorithms revealed that the BRAINSFit B-spline deformable registration algorithm available in SLICER3D was capable of registering small animal PET/CT data sets in less than 5 minutes with an average registration error of .3 mm. The methods used in chapter 3 allowed for the comparison of the spatial distributions of multiple PET tracers imaged at different times. A comparison of FDG and FLT showed that both are positively correlated but that tumor morphology does significantly affect the correlation between the two tracers. An overlap analysis of the high intensity PET regions of FDG and FLT showed that FLT offers additional spatial information to that seen with FDG. In chapter 4 the SARRP allowed for the delivery of planned PET-guided selective dose escalations to a pre-clinical tumor model. This will facilitate future research validating the use of PET for clinical selective dose escalation.

Atmosphere-fire simulation of effects of low-level jets on pyro-convective plume dynamics

Treesearch

Colin C. Simpson; Marwan Katurji; Michael T. Kiefer; Shiyuan Zhong; Joseph J. Charney; Warren E. Heilman; Xindi Bian

2013-01-01

Blow-up fire behaviour can be broadly defined as a rapid escalation in the intensity or forward rate of spread of a wildland fire, and is often accompanied by extreme pyro-convection associated with rapid smoke release and dispersion. Blow-up fire behaviour is difficult to predict and has been linked to firefighter fatalities, making it an important fire management...

Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node–Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Müller, Arndt-Christian, E-mail: arndt-christian.mueller@med.uni-tuebingen.de; Eckert, Franziska; Paulsen, Frank

2016-02-01

Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapymore » sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.« less

Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kok, H. Petra, E-mail: H.P.Kok@amc.uva.nl; Crezee, Johannes; Franken, Nicolaas A.P.

2014-03-01

Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy{sup −1}) and β (Gy{sup −2}) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normalmore » tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment modalities.« less

Role of belly board device in the age of intensity modulated radiotherapy for pelvic irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Estabrook, Neil C.; Bartlett, Gregory K.; Compton, Julia J.

Small bowel dose often represents a limiting factor for radiation treatment of pelvic malignancies. To reduce small bowel toxicity, a belly board device (BBD) with a prone position is often recommended. Intensity modulated radiotherapy (IMRT) could reduce dose to small bowel based on the desired dose-volume constraints. We investigated the efficacy of BBD in conjunction with IMRT. A total of 11 consecutive patients with the diagnosis of rectal cancer, who were candidates for definitive therapy, were selected. Patients were immobilized with BBD in prone position for simulation and treatment. Supine position computed tomography (CT) data were either acquired at themore » same time or during a diagnostic scan, and if existed was used. Target volumes (TV) as well as organs at risk (OAR) were delineated in both studies. Three-dimensional conformal treatment (3DCRT) and IMRT plans were made for both scans. Thus for each patient, 4 plans were generated. Statistical analysis was conducted for maximum, minimum, and mean dose to each structure. When comparing the normalized mean Gross TV dose for the different plans, there was no statistical difference found between the planning types. There was a significant difference in small bowel sparing when using prone position on BBD comparing 3DCRT and IMRT plans, favoring IMRT with a 29.6% reduction in dose (p = 0.007). There was also a statistically significant difference in small bowel sparing when comparing supine position IMRT to prone-BBD IMRT favoring prone-BBD IMRT with a reduction of 30.3% (p = 0.002). For rectal cancer when small bowel could be a limiting factor, prone position using BBD along with IMRT provides the best sparing. We conclude that whenever a dose escalation in rectal cancer is desired where small bowel could be limiting factor, IMRT in conjunction with BBD should be selected.« less

Clinical Implications of the Tumor Volume Reduction Rate in Head-and-Neck Cancer During Definitive Intensity-Modulated Radiotherapy for Organ Preservation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Shih-Neng; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan; Liao, Chih-Ying

2011-03-15

Purpose: To investigate the prognostic value of the volume reduction rate (VRR) in patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Seventy-six patients with oropharyngeal cancer (OPC) and another 76 with hypopharyngeal cancer (HPC) were enrolled in volumetric analysis. All patients received allocated radiotherapy courses. Adaptive computed tomography was done 4 to 5 weeks after the start of IMRT. Primary tumor volume measurement was derived using separate images for the pretreatment gross tumor volume (pGTV) and the interval gross tumor volume. Results: In the OPC group, the pGTV ranged from 6.6 to 242.6 mL (mean, 49.9more » mL), whereas the value of the VRR ranged from 0.014 to 0.74 (mean, 0.43). In HPC patients, the pGTV ranged from 4.1 to 152.4 mL (mean, 35.6 mL), whereas the VRR ranged from -1.15 to 0.79 (mean, 0.33). Multivariate analysis of the primary tumor relapse-free survival for OPC revealed three prognostic factors: T4 tumor (p = 0.0001, hazard ratio 7.38), pGTV {>=}20 mL (p = 0.01, hazard ratio 10.61), and VRR <0.5 (p = 0.001, hazard ratio 6.49). Multivariate analysis of the primary tumor relapse-free survival for HPC showed two prognostic factors: pGTV {>=}30 mL (p = 0.001, hazard ratio 2.87) and VRR <0.5 (p = 0.03, hazard ratio 2.25). Conclusion: The VRR is an outcome predictor for local control in OPC and HPC patients treated with IMRT. Those with large tumor volumes or a VRR <0.5 should be considered for a salvage operation or a dose-escalation scheme.« less

Dosimetric comparison of standard three-dimensional conformal radiotherapy followed by intensity-modulated radiotherapy boost schedule (sequential IMRT plan) with simultaneous integrated boost-IMRT (SIB IMRT) treatment plan in patients with localized carcinoma prostate.

PubMed

Bansal, A; Kapoor, R; Singh, S K; Kumar, N; Oinam, A S; Sharma, S C

2012-07-01

DOSIMETERIC AND RADIOBIOLOGICAL COMPARISON OF TWO RADIATION SCHEDULES IN LOCALIZED CARCINOMA PROSTATE: Standard Three-Dimensional Conformal Radiotherapy (3DCRT) followed by Intensity Modulated Radiotherapy (IMRT) boost (sequential-IMRT) with Simultaneous Integrated Boost IMRT (SIB-IMRT). Thirty patients were enrolled. In all, the target consisted of PTV P + SV (Prostate and seminal vesicles) and PTV LN (lymph nodes) where PTV refers to planning target volume and the critical structures included: bladder, rectum and small bowel. All patients were treated with sequential-IMRT plan, but for dosimetric comparison, SIB-IMRT plan was also created. The prescription dose to PTV P + SV was 74 Gy in both strategies but with different dose per fraction, however, the dose to PTV LN was 50 Gy delivered in 25 fractions over 5 weeks for sequential-IMRT and 54 Gy delivered in 27 fractions over 5.5 weeks for SIB-IMRT. The treatment plans were compared in terms of dose-volume histograms. Also, Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) obtained with the two plans were compared. The volume of rectum receiving 70 Gy or more (V > 70 Gy) was reduced to 18.23% with SIB-IMRT from 22.81% with sequential-IMRT. SIB-IMRT reduced the mean doses to both bladder and rectum by 13% and 17%, respectively, as compared to sequential-IMRT. NTCP of 0.86 ± 0.75% and 0.01 ± 0.02% for the bladder, 5.87 ± 2.58% and 4.31 ± 2.61% for the rectum and 8.83 ± 7.08% and 8.25 ± 7.98% for the bowel was seen with sequential-IMRT and SIB-IMRT plans respectively. For equal PTV coverage, SIB-IMRT markedly reduced doses to critical structures, therefore should be considered as the strategy for dose escalation. SIB-IMRT achieves lesser NTCP than sequential-IMRT.

Tumor volume changes on serial imaging with megavoltage CT for non-small-cell lung cancer during intensity-modulated radiotherapy: how reliable, consistent, and meaningful is the effect?

PubMed

Siker, Malika L; Tomé, Wolfgang A; Mehta, Minesh P

2006-09-01

Adaptive radiotherapy allows treatment plan modification based on data obtained during treatment. Assessing volume changes during treatment is now possible with intratreatment imaging capabilities on radiotherapy devices. This study assesses non-small-cell lung cancer (NSCLC) volume changes during treatment with conformal intensity-modulated radiotherapy by evaluating serial megavoltage computed tomography (MVCT) scans, with a specific emphasis on the frequency, reliability, and meaningfulness of these changes. Megavoltage CTs were retrospectively reviewed for 25 patients treated with the TomoTherapy Hi-Art system at the University of Wisconsin. Twenty-one patients received definitive radiotherapy, 4 with extracranial stereotactic radioablation (60 Gy in five fractions) and 17 on a dose-per-fraction escalation protocol (57-80.5 Gy in 25 fractions). Four patients were treated palliatively (22-30 Gy in 8 to 10 fractions). Gross tumor volumes were contoured on serial MVCTs at weekly intervals. Each patient had 4 to 25 scans, including at least one at the beginning, midway, and one at the end of treatment. At completion of treatment, no patient demonstrated a complete response. Partial response occurred in 3 (12%) and marginal response was noted in 5 (20%). The remaining 17 patients (68%) showed stable disease. The minimum "scorable threshold" for volume discrepancy between scans to account for interscan assessment variability was set at >25% volume change; 10 patients (40%) had >25% tumor regression. None of the patients treated ablatively or palliatively showed tumor regression during treatment. Although gross tumor regression during treatment may be objectively measured using MVCTs, substantial volumetric decrease occurs only in a minority. The clinical significance of this regression is questionable, because there is no way to document histologic tumor clearance, and therefore field reductions during radiotherapy cannot be recommended.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.

Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of thismore » novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for small–tumor target patients. This optimizer will be used in an upcoming feasibility trial on LET{sub d} painting for radioresistant tumors.« less

[Ethic rounds in intensive care. Possible instrument for a clinical-ethical assessment in intensive care units].

PubMed

Scheffold, N; Paoli, A; Gross, J; Riemann, U; Hennersdorf, M

2012-10-01

Ethical problems, such as medical end-of-life decisions or withdrawing life-sustaining treatment are viewed as an essential task in intensive care units. This article presents the ethics rounds as an instrument for evaluation of ethical problems in intensive care medicine units. The benchmarks of ethical reflection during the ethics rounds are considerations of ethical theory of principle-oriented medical ethics. Besides organizational aspects and the institutional framework, the role of the ethicist is described. The essential evaluation steps, as a basis of the ethics rounds are presented. In contrast to the clinical ethics consultation, the ethicist in the ethics rounds model is integrated as a member of the ward round team. Therefore ethical problems may be identified and analyzed very early before the conflict escalates. This preventive strategy makes the ethics rounds a helpful instrument in intensive care units.

Multiple cues produced by a robotic fish modulate aggressive behaviour in Siamese fighting fishes.

PubMed

Romano, Donato; Benelli, Giovanni; Donati, Elisa; Remorini, Damiano; Canale, Angelo; Stefanini, Cesare

2017-07-05

The use of robotics to establish social interactions between animals and robots, represents an elegant and innovative method to investigate animal behaviour. However, robots are still underused to investigate high complex and flexible behaviours, such as aggression. Here, Betta splendens was tested as model system to shed light on the effect of a robotic fish eliciting aggression. We evaluated how multiple signal systems, including a light stimulus, affect aggressive responses in B. splendens. Furthermore, we conducted experiments to estimate if aggressive responses were triggered by the biomimetic shape of fish replica, or whether any intruder object was effective as well. Male fishes showed longer and higher aggressive displays as puzzled stimuli from the fish replica increased. When the fish replica emitted its full sequence of cues, the intensity of aggression exceeded even that produced by real fish opponents. Fish replica shape was necessary for conspecific opponent perception, evoking significant aggressive responses. Overall, this study highlights that the efficacy of an artificial opponent eliciting aggressive behaviour in fish can be boosted by exposure to multiple signals. Optimizing the cue combination delivered by the robotic fish replica may be helpful to predict escalating levels of aggression.

Simultaneous modulated accelerated radiation therapy for esophageal cancer: a feasibility study.

PubMed

Zhang, Wu-Zhe; Chen, Jian-Zhou; Li, De-Rui; Chen, Zhi-Jian; Guo, Hong; Zhuang, Ting-Ting; Li, Dong-Sheng; Zhou, Ming-Zhen; Chen, Chuang-Zhen

2014-10-14

To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC). Computed tomography (CT) datasets of 10 patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART, conventionally-fractionated three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (cf-IMRT) plans, respectively. The gross target volume (GTV) of the esophagus, positive regional lymph nodes (LN), and suspected lymph nodes (LN ±) were contoured for each patient. The clinical target volume (CTV) was delineated with 2-cm longitudinal and 0.5- to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±). For the SMART plans, there were two planning target volumes (PTVs): PTV66 = (GTV + LN) + 0.5 cm and PTV54 = CTV + 0.5 cm. For the 3DCRT and cf-IMRT plans, there was only a single PTV: PTV60 = CTV + 0.5 cm. The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54. The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F. All the plans were generated on the Eclipse 10.0 treatment planning system. Fulfillment of the dose criteria for the PTVs received the highest priority, followed by the spinal cord, heart, and lungs. The dose-volume histograms were compared. Clinically acceptable plans were achieved for all the SMART, cf-IMRT, and 3DCRT plans. Compared with the 3DCRT plans, the SMART plans increased the dose delivered to the primary tumor (66 Gy vs 60 Gy), with improved sparing of normal tissues in all patients. The Dmax of the spinal cord, V20 of the lungs, and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows: 38.5 ± 2.0 vs 44.7 ± 0.8 (P = 0.002), 17.1 ± 4.0 vs 25.8 ± 5.0 (P = 0.000), 14.4 ± 7.5 vs 21.4 ± 11.1 (P = 0.000), and 4.9 ± 3.4 vs 12.9 ± 7.6 (P = 0.000), respectively. In contrast to the cf-IMRT plans, the SMART plans permitted a simultaneous dose escalation (6 Gy) to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord, for which no significant difference was found. SMART offers the potential for a 6 Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues.

Simultaneous modulated accelerated radiation therapy for esophageal cancer: A feasibility study

PubMed Central

Zhang, Wu-Zhe; Chen, Jian-Zhou; Li, De-Rui; Chen, Zhi-Jian; Guo, Hong; Zhuang, Ting-Ting; Li, Dong-Sheng; Zhou, Ming-Zhen; Chen, Chuang-Zhen

2014-01-01

AIM: To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC). METHODS: Computed tomography (CT) datasets of 10 patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART, conventionally-fractionated three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (cf-IMRT) plans, respectively. The gross target volume (GTV) of the esophagus, positive regional lymph nodes (LN), and suspected lymph nodes (LN±) were contoured for each patient. The clinical target volume (CTV) was delineated with 2-cm longitudinal and 0.5- to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±). For the SMART plans, there were two planning target volumes (PTVs): PTV66 = (GTV + LN) + 0.5 cm and PTV54 = CTV + 0.5 cm. For the 3DCRT and cf-IMRT plans, there was only a single PTV: PTV60 = CTV + 0.5 cm. The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54. The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F. All the plans were generated on the Eclipse 10.0 treatment planning system. Fulfillment of the dose criteria for the PTVs received the highest priority, followed by the spinal cord, heart, and lungs. The dose-volume histograms were compared. RESULTS: Clinically acceptable plans were achieved for all the SMART, cf-IMRT, and 3DCRT plans. Compared with the 3DCRT plans, the SMART plans increased the dose delivered to the primary tumor (66 Gy vs 60 Gy), with improved sparing of normal tissues in all patients. The Dmax of the spinal cord, V20 of the lungs, and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows: 38.5 ± 2.0 vs 44.7 ± 0.8 (P = 0.002), 17.1 ± 4.0 vs 25.8 ± 5.0 (P = 0.000), 14.4 ± 7.5 vs 21.4 ± 11.1 (P = 0.000), and 4.9 ± 3.4 vs 12.9 ± 7.6 (P = 0.000), respectively. In contrast to the cf-IMRT plans, the SMART plans permitted a simultaneous dose escalation (6 Gy) to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord, for which no significant difference was found. CONCLUSION: SMART offers the potential for a 6 Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues. PMID:25320535

Salvage image guided radiation therapy to the prostate after cryotherapy failure.

PubMed

Hopper, Austin B; Sandhu, Ajay P S; Parsons, J Kellogg; Rose, Brent; Einck, John P

2018-01-01

Cryotherapy is an option for the primary treatment of localized prostate cancer, along with radical prostatectomy, external beam radiation therapy, and brachytherapy. Although it is known that local recurrence can occur in >20% of patients treated with primary cryotherapy, unfortunately there is a paucity of data on later salvage treatments. The use of external beam radiation therapy is an attractive option after cryotherapy failure, but there is little data on its efficacy and toxicity. We evaluated the biochemical control and complication rates of salvage dose-escalated image guided intensity modulated radiation therapy (IG-IMRT) after cryotherapy failure. Patients who were treated at our institution from 2005 to 2016 were reviewed for those who underwent cryotherapy as initial treatment followed by salvage IGRT. Patients were treated with dose-escalated IG-IMRT using standard treatment margins of 3 mm posterior and 7 mm in all other directions and daily cone beam computed tomography or kv imaging to implanted fiducial markers. Biochemical progression was defined in accordance with the Phoenix consensus conference definition. Eight patients were identified as having received post-cryotherapy salvage radiation within the study period. The median total dose was 77.7 Gy (range, 75.6-81.0 Gy). Median follow-up was 55 months (range, 6-88 months). Six patients remained biochemically controlled at the latest follow-up. One patient developed distant metastases after 22 months and one experienced biochemical failure at 30 months with no evidence of distant metastases. No patients experienced acute gastrointestinal toxicities of grade 2 or higher. There were no cases of late gastrointestinal or genitourinary toxicity. High-dose IG-IMRT results in high rates of salvage and extremely low rates of serious late toxicity for patients with locally recurrent prostate cancer after cryotherapy. Although the results are encouraging, given the small number of patients in this and other series, we remain cautious with regard to this treatment and believe the use of salvage radiation therapy after cryotherapy warrants further study.

Decision regret in men undergoing dose-escalated radiation therapy for prostate cancer.

PubMed

Steer, Anna N; Aherne, Noel J; Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques; Shakespeare, Thomas P

2013-07-15

Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Decision Regret in Men Undergoing Dose-Escalated Radiation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steer, Anna N.; Aherne, Noel J., E-mail: noel.aherne@ncahs.health.nsw.gov.au; Rural Clinical School Faculty of Medicine, University of New South Wales, Coffs Harbour

2013-07-15

Purpose: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. Methods and Materials: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by meansmore » of a validated questionnaire. Results: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Conclusion: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.« less

A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas.

PubMed

Thompson, Reid F; Mayekar, Sonal U; Zhai, Huifang; Both, Stefan; Apisarnthanarax, Smith; Metz, James M; Plastaras, John P; Ben-Josef, Edgar

2014-08-01

Uncontrolled local growth is the cause of death in ∼ 30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6-53.8 and 34.9-52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.

IMRT and 3D conformal radiotherapy with or without elective nodal irradiation in locally advanced NSCLC: A direct comparison of PET-based treatment planning.

PubMed

Fleckenstein, Jochen; Kremp, Katharina; Kremp, Stephanie; Palm, Jan; Rübe, Christian

2016-02-01

The potential of intensity-modulated radiation therapy (IMRT) as opposed to three-dimensional conformal radiotherapy (3D-CRT) is analyzed for two different concepts of fluorodeoxyglucose positron emission tomography (FDG PET)-based target volume delineation in locally advanced non-small cell lung cancer (LA-NSCLC): involved-field radiotherapy (IF-RT) vs. elective nodal irradiation (ENI). Treatment planning was performed for 41 patients with LA-NSCLC, using four different planning approaches (3D-CRT-IF, 3D-CRT-ENI, IMRT-IF, IMRT-ENI). ENI included a boost irradiation after 50 Gy. For each plan, maximum dose escalation was calculated based on prespecified normal tissue constraints. The maximum prescription dose (PD), tumor control probability (TCP), conformal indices (CI), and normal tissue complication probabilities (NTCP) were analyzed. IMRT resulted in statistically significant higher prescription doses for both target volume concepts as compared with 3D-CRT (ENI: 68.4 vs. 60.9 Gy, p < 0.001; IF: 74.3 vs. 70.1 Gy, p < 0.03). With IMRT-IF, a PD of at least 66 Gy was achieved for 95 % of all plans. For IF as compared with ENI, there was a considerable theoretical increase in TCP (IMRT: 27.3 vs. 17.7 %, p < 0.00001; 3D-CRT: 20.2 vs. 9.9 %, p < 0.00001). The esophageal NTCP showed a particularly good sparing with IMRT vs. 3D-CRT (ENI: 12.3 vs. 30.9 % p < 0.0001; IF: 15.9 vs. 24.1 %; p < 0.001). The IMRT technique and IF target volume delineation allow a significant dose escalation and an increase in TCP. IMRT results in an improved sparing of OARs as compared with 3D-CRT at equivalent dose levels.

U.S. Marine Corps S&T Strategic Plan: Leading Edge Technology for the Marines of Tomorrow

DTIC Science & Technology

2009-07-29

in monitoring exercise intensity, frequency, duration, recovery, and/or specific physiological indicators of aerobic training to prevent over-or...plan that focus specifically on Escalation of Force and Irregular Wa, fa",. III aoJditiuII, we have muvcd Training & Education from an Annex into...vision by developing Marine Corps warfighting concepts and determines required capabilities through Doctrine, Organization, Training , Materiel

XTEN Nationwide EMS Proposal.

DTIC Science & Technology

1979-01-01

revenue producers.20 It is the co on carriers position to sell as much service as possible to users of the network while DCS is designed to provide...escalating costs in the United States Postal Service ( USPS ) (due to its labor intensive nature) and declining costs in the EMS industries (due to...Carrier Assoc. for Tele- communications (CCAT), GTE Service Corporation (GTE), Litton Micro- wave Cooking Products , Inc., Microband Corporation of American

When Action-Inaction Framing Leads to Higher Escalation of Commitment: A New Inaction-Effect Perspective on the Sunk-Cost Fallacy.

PubMed

Feldman, Gilad; Wong, Kin Fai Ellick

2018-04-01

Escalation of commitment to a failing course of action occurs in the presence of (a) sunk costs, (b) negative feedback that things are deviating from expectations, and (c) a decision between escalation and de-escalation. Most of the literature to date has focused on sunk costs, yet we offer a new perspective on the classic escalation-of-commitment phenomenon by focusing on the impact of negative feedback. On the basis of the inaction-effect bias, we theorized that negative feedback results in the tendency to take action, regardless of what that action may be. In four experiments, we demonstrated that people facing escalation-decision situations were indeed action oriented and that framing escalation as action and de-escalation as inaction resulted in a stronger tendency to escalate than framing de-escalation as action and escalation as inaction (mini-meta-analysis effect d = 0.37, 95% confidence interval = [0.21, 0.53]).

Toward a planning scheme for emission guided radiation therapy (EGRT): FDG based tumor tracking in a metastatic breast cancer patient

PubMed Central

Fan, Qiyong; Nanduri, Akshay; Yang, Jaewon; Yamamoto, Tokihiro; Loo, Billy; Graves, Edward; Zhu, Lei; Mazin, Samuel

2013-01-01

Purpose: Emission guided radiation therapy (EGRT) is a new modality that uses PET emissions in real-time for direct tumor tracking during radiation delivery. Radiation beamlets are delivered along positron emission tomography (PET) lines of response (LORs) by a fast rotating ring therapy unit consisting of a linear accelerator (Linac) and PET detectors. The feasibility of tumor tracking and a primitive modulation method to compensate for attenuation have been demonstrated using a 4D digital phantom in our prior work. However, the essential capability of achieving dose modulation as in conventional intensity modulated radiation therapy (IMRT) treatments remains absent. In this work, the authors develop a planning scheme for EGRT to accomplish sophisticated intensity modulation based on an IMRT plan while preserving tumor tracking. Methods: The planning scheme utilizes a precomputed LOR response probability distribution to achieve desired IMRT planning modulation with effects of inhomogeneous attenuation and nonuniform background activity distribution accounted for. Evaluation studies are performed on a 4D digital patient with a simulated lung tumor and a clinical patient who has a moving breast cancer metastasis in the lung. The Linac dose delivery is simulated using a voxel-based Monte Carlo algorithm. The IMRT plan is optimized for a planning target volume (PTV) that encompasses the tumor motion using the MOSEK package and a Pinnacle3™ workstation (Philips Healthcare, Fitchburg, WI) for digital and clinical patients, respectively. To obtain the emission data for both patients, the Geant4 application for tomographic emission (GATE) package and a commercial PET scanner are used. As a comparison, 3D and helical IMRT treatments covering the same PTV based on the same IMRT plan are simulated. Results: 3D and helical IMRT treatments show similar dose distribution. In the digital patient case, compared with the 3D IMRT treatment, EGRT achieves a 15.1% relative increase in dose to 95% of the gross tumor volume (GTV) and a 31.8% increase to 50% of the GTV. In the patient case, EGRT yields a 15.2% relative increase in dose to 95% of the GTV and a 20.7% increase to 50% of the GTV. The organs at risk (OARs) doses are kept similar or lower for EGRT in both cases. Tumor tracking is observed in the presence of planning modulation in all EGRT treatments. Conclusions: As compared to conventional IMRT treatments, the proposed EGRT planning scheme allows an escalated target dose while keeping dose to the OARs within the same planning limits. With the capabilities of incorporating planning modulation and accurate tumor tracking, EGRT has the potential to greatly improve targeting in radiation therapy and enable a practical and effective implementation of 4D radiation therapy for planning and delivery. PMID:23927305

Revisiting the definition of dose-limiting toxicities in paediatric oncology phase I clinical trials: An analysis from the Innovative Therapies for Children with Cancer Consortium.

PubMed

Bautista, Francisco; Moreno, Lucas; Marshall, Lynley; Pearson, Andrew D J; Geoerger, Birgit; Paoletti, Xavier

2017-11-01

Dose-escalation trials aim to identify the maximum tolerated dose and, importantly, the recommended phase II dose (RP2D) and rely on the occurrence of dose-limiting toxicities (DLTs) during the first treatment cycle. Molecularly targeted agents (MTAs) often follow continuous and prolonged administrations, displaying a distinct toxicity profile compared to conventional chemotherapeutics, and classical DLT criteria might not be appropriate to evaluate MTAs' toxicity. We investigated this issue in children. The Innovative Therapies for Children with Cancer Consortium (ITCC) phase I trials of novel anticancer agents between 2004 and 2015 were analysed. Data from investigational product, trial design, items defining DLT/RP2D were extracted. A survey on dose-escalation process, DLTs and RP2D definition was conducted among the ITCC clinical trials committee members. Thirteen phase I trials with 15 dose-escalation cohorts were analysed. They explored 11 MTAs and 2 novel cytotoxics; 12 evaluated DLT during cycle 1. Definition of DLT was heterogeneous: Grade III-IV haematologic toxicities that were transient or asymptomatic and grade III-IV non-haematological toxicities manageable with adequate supportive care were often excluded, whereas some included dose intensity or grade II toxicities into DLT. None of the studies considered delayed toxicity into the RP2D definition. DLTs should be homogeneously defined across trials, limiting the number of exceptions due to specific toxicities. Dose escalation should still be based on safety data from cycle 1, but delayed and overall toxicities, pharmacokinetic parameters and pharmacodynamic data should be considered to refine the final RP2D. The evaluation of long-term toxicity in the developing child cannot be adequately addressed in early trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Extending the data rate of non-line-of-sight UV communication with polarization modulation

NASA Astrophysics Data System (ADS)

Yin, Hongwei; Jia, Honghui; Zhang, Hailiang; Wang, Xiaofeng; Chang, Shengli; Yang, Juncai

2012-10-01

With low radiation background of solar-blind UV and strong scattering of UV photons by atmospheric particles, UV communication can be made use of to set up a non-line-of-sight (NLOS) free-space optical communication link. Polarization modulation, besides the traditional intensity modulation, is presented to enhance the data rate of the UV communication system. The configuration and the working process of the dually modulated UV communication system with intensity modulation and polarization, the theoretical evaluation of polarization modulation, and a numerical of the scattering matrix are presented, with the conclusion that polarization modulation is achievable. By adding the polarizing devices and changing the coding procedures, the existing singly-modulated UV communication systems with intensity modulation are easily modified to be dually-modulated ones with polarization modulation and intensity modulation. Ideally speaking, the data rate of the dually-modulated UV communication system is the product of the data rate of the singly modulated system and the number of polarization modulation.

An Examination of Escalation in Burglaries Committed by Sexual Offenders.

PubMed

Pedneault, Amelie; Harris, Danielle A; Knight, Raymond A

2015-10-01

Research in the field of sexual aggression often assumes escalation in the criminal careers of sexual offenders. Sexual offenders are thought to begin their criminal careers with non-contact sexual offenses or non-sexual offenses and then escalate to more serious crimes, specifically sexual violence. The commission of one crime in particular--burglary--has been found to be a predictor of future violence in sexual offenders. The present study investigated the nature and extent of escalation in the criminal histories of 161 sex offenders who committed at least two burglaries. Six types of escalations were considered: type of burglary, occupancy, violence, weapon, frequency, and the victim-offender relationship. Escalators and non-escalators were compared, differences between the groups were reviewed, and the cumulative effect of various forms of escalation was analyzed. Results indicated that escalators and non-escalators could be differentiated on a number of important dimensions that might assist in the earlier detection of subsequently more dangerous offenders. © The Author(s) 2014.

The feasibility and benefits of using volumetric arc therapy in patients with brain metastases: a systematic review.

PubMed

Andrevska, Adriana; Knight, Kellie A; Sale, Charlotte A

2014-12-01

Radiotherapy management of patients with brain metastases most commonly involve a whole-brain radiation therapy (WBRT) regime, as well as newer techniques such as stereotactic radiosurgery (SRS) and intensity modulated radiotherapy (IMRT). The long treatment times incurred by these techniques indicates the need for a novel technique that has shorter treatment times, whilst still producing highly conformal treatment with the potential to deliver escalated doses to the target area. Volumetric modulated arc therapy (VMAT) is a dynamic, highly conformal technique that may deliver high doses of radiation through a single gantry arc and reduce overall treatment times. The aim of this systematic review is to determine the feasibility and benefits of VMAT treatment in regard to overall survival rates and local control in patients with brain metastases, in comparison with patients treated with WBRT, SRS and IMRT. A search of the literature identified 23 articles for the purpose of this review. Articles were included on the basis they were human-based studies, with sample sizes of more than five patients who were receiving treatment for 1-10 metastatic brain lesions. VMAT was found to be highly conformal, have a reduced treatment delivery time and incurred no significant toxicities in comparison with WBRT, SRS and IMRT. Compared to other treatment techniques, VMAT proved to have fewer toxicities than conventional WBRT, shorter treatment times than SRS and similar dose distributions to IMRT plans. Future prospective studies are needed to accurately assess the prognostic benefits of VMAT as well as the occurrence of late toxicities.

SU-E-T-126: Dosimetric Comparisons of VMAT, IMRT and 3DCRT for Locally Advanced Rectal Cancer with Simultaneous Integrated Boost

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, J; Wang, J; Zhang, Z

2014-06-01

Purpose: The purpose of this study is to compare the dosimetric differences among volumetric modulated arc therapy (VMAT), fixed-field intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for the preoperative locally advanced rectal cancer (LARC). Methods: Ten LARC patients treated in our department using the simultaneous escalate strategy were retrospectively analyzed in this study. All patients had T3 with N+/− and were treated with IMRT. Two additional VMAT and 3DCRT plans were created for each patient. Both IMRT and VMAT had similar optimization objectives. The prescription was 50Gy to the PTV and 55Gy to the GTV. The target coveragemore » and organs at risk were compared for all the techniques.The paired, two-tailed Wilcoxcon signed-rank test was applied for statistical analysis. Results: IMRT and VMAT plans achieved comparable tumor response except for the conformality index (1.07 vs 1.19 and 1.08 vs 1.03 of IMRT vs VMAT for PTV-G and PTV-C respectively). Compared to VMAT, IMRT showed superior or similar dose sparing in the small bowel, bladder, femoral head. Both IMRT and VMAT had better organs at risk sparing and homogeneity index of PTV-G. Conclusion: All 3DCRT, IMRT and VMAT meet the prescript. The IMRT and VMAT provided comparable dosemitric parameters for target volume. IMRT shows better sparing for small bowel, bladder, femoral heads and normal tissue to 3DCRT and VMAT.« less

THE DEAL WITH IRAN IS THE BEST-CASE SCENARIO THE INTERNATIONAL COMMUNITY COULD ACHIEVE IN THE CURRENT GEOPOLITICAL ENVIRONMENT

DTIC Science & Technology

2016-02-16

that significant contributions to the successful negotiations were the geopolitical realities of the effects of escalating economic sanctions in Iran...since 2010. Three years later started a cycle of intense international negotiations . 4 The Nuclear Deal On July 14, 2015, negotiators from...with many international negotiations and agreements, brings with it varying expectations. The complexity of the process before the agreement is

Escalation and Intrawar Deterrence During Limited Wars in the Middle East

DTIC Science & Technology

2009-09-01

informed by a solid understanding of the potential variation in the escalatory process as U.S. leaders work with the UN to try to establish cease...discern Arab intensions within their own psychological framework which emphasized the searing memory of the most tragic episodes in the history of... information is obtained, processed , and presented to foreign leaders. The intelligence services of foreign nations may not be providing a foreign

Meal Module, Tray Pack 36-Persons

DTIC Science & Technology

1987-08-27

4184 Canadian Bacon 8905-01-1 51-2488 Escal loped Potatoes 8940-01-147-6362 Grape Juice, Instant 8915-01-010-1471 Disposable Unit (Table A-2) as...Chocolate Pudding 8940-01-159-1569 Orange, Juice, Instant 8915-00-530-3414 Disposable Unit (Table A-2) as listed Condiments (Table A-3) as listed...Breakfast 3 Pineapple w/Syrup 8915-00-170-5127 Chicken ala King 8940-01-154-3525 Buttered Noodles 8940-01-151-5844 Apple Dessert 8940-01-147-7855 Grape

Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis.

PubMed

Howlett, Christina; Snedecor, Sonya J; Landsburg, Daniel J; Svoboda, Jakub; Chong, Elise A; Schuster, Stephen J; Nasta, Sunita Dwivedy; Feldman, Tatyana; Rago, Allison; Walsh, Kristy M; Weber, Scott; Goy, Andre; Mato, Anthony

2015-08-01

'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse large B-cell lymphomas (DLBCL). Consequently, dose-intensive (DI) therapies and/or consolidation with high-dose therapy and transplant have been explored in DHL, although benefit has been debated. This meta-analysis compared survival outcomes in DHL patients receiving dose-escalated regimens [DI: R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) or R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine); or intermediate-dose: R-EPOCH (rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone)] versus standard-dose regimens (R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line setting. Data were synthesized to estimate hazard ratios of dose-escalated treatments versus R-CHOP using a Weibull proportional hazards model within a Bayesian meta-analysis framework. Eleven studies examining 394 patients were included. Patients were treated with either front-line R-CHOP (n = 180), R-EPOCH (n = 91), or R-Hyper-CVAD/rituximab, methotrexate, cytarabine (R-M/C), R-CODOX-M/R-IVAC (DI) (n = 123). Our meta-analysis revealed that median progression-free survival (n = 350) for the R-CHOP, R-EPOCH and DI groups was 12·1, 22·2, and 18·9 months, respectively. First-line treatment with R-EPOCH significantly reduced the risk of a progression compared with R-CHOP (relative risk reduction of 34%; P = 0·032); however, overall survival (n = 374) was not significantly different across treatment approaches. A subset of patients might benefit from intensive induction with/without transplant. Further investigation into the role of transplant and novel therapy combinations is necessary. © 2015 John Wiley & Sons Ltd.

A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management.

PubMed

Holdcroft, Anita; Maze, Mervyn; Doré, Caroline; Tebbs, Susan; Thompson, Simon

2006-05-01

Cannabinoids have dose-related antinociceptive effects in animals. This clinical study aimed to investigate whether a single oral dose of cannabis plant extract (Cannador; Institute for Clinical Research, IKF, Berlin, Germany) could provide pain relief with minimal side effects for postoperative pain. Patients (aged 18-75 yr) were recruited and consented before surgery if patient-controlled analgesia was planned for provision of postoperative pain relief. Each patient received a single dose of 5, 10, or 15 mg Cannador if he or she had at least moderate pain after stopping patient-controlled analgesia. Starting with 5 mg, dose escalation was based on the number of patients requesting rescue analgesia and adverse effects. Pain relief, pain intensity, and side effects were recorded over 6 h and analyzed using tests for trend with dose. Rescue analgesia was requested by all 11 patients (100%) receiving 5 mg, 15 of 30 patient (50%) receiving 10 mg, and 6 of 24 patients (25%) receiving 15 mg Cannador (log rank test for trend in time to rescue analgesia with dose P < 0.001). There were also significant trends across the escalating dose groups for decreasing pain intensity at rest (P = 0.01), increasing sedation (P = 0.03), and more adverse events (P = 0.002). The number needed to treat to prevent one rescue analgesia request for the 10-mg and 15-mg doses, relative to 5 mg, were 2.0 (95% confidence interval, 1.5-3.1) and 1.3 (95% confidence interval, 1.1-1.7), respectively. The study was terminated because of a serious vasovagal adverse event in a patient receiving 15 mg. These significant dose-related improvements in rescue analgesia requirements in the 10 mg and 15 mg groups provide a number needed to treat that is equivalent to many routinely used analgesics without frequent adverse effects.

Smartphone-Based Escalator Recognition for the Visually Impaired

PubMed Central

Nakamura, Daiki; Takizawa, Hotaka; Aoyagi, Mayumi; Ezaki, Nobuo; Mizuno, Shinji

2017-01-01

It is difficult for visually impaired individuals to recognize escalators in everyday environments. If the individuals ride on escalators in the wrong direction, they will stumble on the steps. This paper proposes a novel method to assist visually impaired individuals in finding available escalators by the use of smartphone cameras. Escalators are recognized by analyzing optical flows in video frames captured by the cameras, and auditory feedback is provided to the individuals. The proposed method was implemented on an Android smartphone and applied to actual escalator scenes. The experimental results demonstrate that the proposed method is promising for helping visually impaired individuals use escalators. PMID:28481270

Increasing human dominance of tropical forests.

PubMed

Lewis, Simon L; Edwards, David P; Galbraith, David

2015-08-21

Tropical forests house over half of Earth's biodiversity and are an important influence on the climate system. These forests are experiencing escalating human influence, altering their health and the provision of important ecosystem functions and services. Impacts started with hunting and millennia-old megafaunal extinctions (phase I), continuing via low-intensity shifting cultivation (phase II), to today's global integration, dominated by intensive permanent agriculture, industrial logging, and attendant fires and fragmentation (phase III). Such ongoing pressures, together with an intensification of global environmental change, may severely degrade forests in the future (phase IV, global simplification) unless new "development without destruction" pathways are established alongside climate change-resilient landscape designs. Copyright © 2015, American Association for the Advancement of Science.

The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.

PubMed

Burnett, Alan K; Milligan, Donald; Goldstone, Anthony; Prentice, Archibald; McMullin, Mary-Frances; Dennis, Michael; Sellwood, Elizabeth; Pallis, Monica; Russell, Nigel; Hills, Robert K; Wheatley, Keith

2009-05-01

The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.

Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription.

PubMed

Hoffmann, Aswin L; Huizenga, Henk; Kaanders, Johannes H A M

2013-03-07

In current practice, patients scheduled for radiotherapy are treated according to 'rigid' protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians' or patients' choices for dose (de-)escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels.

Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription

PubMed Central

2013-01-01

Background In current practice, patients scheduled for radiotherapy are treated according to ‘rigid’ protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Methods Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. Results On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians’ or patients’ choices for dose (de-)escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. Conclusions The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels. PMID:23497640

Light-intensity modulator withstands high heat fluxes

NASA Technical Reports Server (NTRS)

Maples, H. G.; Strass, H. K.

1966-01-01

Mechanism modulates and controls the intensity of luminous radiation in light beams associated with high-intensity heat flux. This modulator incorporates two fluid-cooled, externally grooved, contracting metal cylinders which when rotated about their longitudinal axes present a circular aperture of varying size depending on the degree of rotation.

THE EFFECTS OF FIXED VERSUS ESCALATING REINFORCEMENT SCHEDULES ON SMOKING ABSTINENCE

PubMed Central

Romanowich, Paul; Lamb, R. J.

2015-01-01

Studies indicate that when abstinence is initiated, escalating reinforcement schedules maintain continuous abstinence longer than fixed reinforcement schedules. However, these studies were conducted for shorter durations than most clinical trials and also resulted in larger reinforcer value for escalating participants during the 1st week of the experiment. We tested whether escalating reinforcement schedules maintained abstinence longer than fixed reinforcement schedules in a 12-week clinical trial. Smokers (146) were randomized to an escalating reinforcement schedule, a fixed reinforcement schedule, or a control condition. Escalating reinforcement participants received $5.00 for their first breath carbon monoxide (CO) sample <3 ppm, with a $0.50 increase for each consecutive sample. Fixed reinforcement participants received $19.75 for each breath CO sample <3 ppm. Control participants received payments only for delivering a breath CO sample. Similar proportions of escalating and fixed reinforcement participants met the breath CO criterion at least once. Escalating reinforcement participants maintained criterion breath CO levels longer than fixed reinforcement and control participants. Similar to previous short-term studies, escalating reinforcement schedules maintained longer durations of abstinence than fixed reinforcement schedules during a clinical trial. PMID:25640764

Longitudinal density modulation and energy conversion in intense beams.

PubMed

Harris, J R; Neumann, J G; Tian, K; O'Shea, P G

2007-08-01

Density modulation of charged particle beams may occur as a consequence of deliberate action, or may occur inadvertently because of imperfections in the particle source or acceleration method. In the case of intense beams, where space charge and external focusing govern the beam dynamics, density modulation may, under some circumstances, be converted to velocity modulation, with a corresponding conversion of potential energy to kinetic energy. Whether this will occur depends on the properties of the beam and the initial modulation. This paper describes the evolution of discrete and continuous density modulations on intense beams and discusses three recent experiments related to the dynamics of density-modulated electron beams.

Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Jeffrey Y.C., E-mail: jwong@coh.org; Forman, Stephen; Somlo, George

2013-01-01

Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamidemore » (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to dose-limiting toxicities. Future efforts will focus on whether further dose escalation with CY/VP16 is safe, with the goal of improving disease control in this high-risk population.« less

Comparison of anisotropic aperture based intensity modulated radiotherapy with 3D-conformal radiotherapy for the treatment of large lung tumors.

PubMed

Simeonova, Anna; Abo-Madyan, Yasser; El-Haddad, Mostafa; Welzel, Grit; Polednik, Martin; Boggula, Ramesh; Wenz, Frederik; Lohr, Frank

2012-02-01

IMRT allows dose escalation for large lung tumors, but respiratory motion may compromise delivery. A treatment plan that modulates fluence predominantly in the transversal direction and leaves the fluence identical in the direction of the breathing motion may reduce this problem. Planning-CT-datasets of 20 patients with Stage I-IV non small cell lung cancer (NSCLC) formed the basis of this study. A total of two IMRT plans and one 3D plan were created for each patient. Prescription dose was 60 Gy to the CTV and 70 Gy to the GTV. For the 3D plans an energy of 18 MV photons was used. IMRT plans were calculated for 6 MV photons with 13 coplanar and with 17 noncoplanar beams. Robustness of the used method of anisotropic modulation toward breathing motion was tested in a 13-field IMRT plan. As a consequence of identical prescription doses, mean target doses were similar for 3D and IMRT. Differences between 3D and 13- and 17-field IMRT were significant for CTV Dmin (43 Gy vs. 49.1 Gy vs. 48.6 Gy; p<0.001) and CTV D(95) (53.2 Gy vs. 55.0 Gy vs. 55.4 Gy; p=0.001). The D(mean) of the contralateral lung was significantly lower in the 17-field plans (17-field IMRT vs. 13- vs. 3D: 12.5 Gy vs. 14.8 Gy vs. 15.8 Gy: p<0.05). The spinal cord dose limit of 50 Gy was always respected in IMRT plans and only in 17 of 20 3D-plans. Heart D(max) was only marginally reduced with IMRT (3D vs. 13- vs. 17-field IMRT: 38.2 Gy vs. 36.8 Gy vs. 37.8 Gy). Simulated breathing motion caused only minor changes in the IMRT dose distribution (~0.5-1 Gy). Anisotropic modulation of IMRT improves dose delivery over 3D-RT and renders IMRT plans robust toward breathing induced organ motion, effectively preventing interplay effects. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer.

PubMed

Bruera, Gemma; Massacese, Silvia; Galvano, Antonio; Mas, Antonella Dal; Guadagni, Stefano; Calvisi, Giuseppe; Ciacco, Eugenio; Russo, Antonio; Ricevuto, Enrico

2018-04-17

Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity. Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m 2 /d 1-2, 8-9, 15-16, 22-23, with 100 mg/m 2 /d increase for dose level; DTX 50 mg/m 2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m 2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned. Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m 2 /d and 80 mg/m 2 , respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leucopenia 20%, hypoalbuminemia 10%, mucositis 10%, asthenia 20%. Limiting toxicity syndromes were 30%, 25% in young-elderly, all multiple site. Objective response rate intent-to-treat 60%, disease control rate 90%. After 15 months follow-up, progression-free and overall survival, 6 and 17 months, respectively. First line intensive FD/FOx regimen adding DXT/5-FU/OXP can be safely administered at recommended doses in advanced GC, with promising high activity and efficacy.

Emergency Department Escalation in Theory and Practice: A Mixed-Methods Study Using a Model of Organizational Resilience.

PubMed

Back, Jonathan; Ross, Alastair J; Duncan, Myanna D; Jaye, Peter; Henderson, Katherine; Anderson, Janet E

2017-11-01

Escalation policies are used by emergency departments (EDs) when responding to an increase in demand (eg, a sudden inflow of patients) or a reduction in capacity (eg, a lack of beds to admit patients). The policies aim to maintain the ability to deliver patient care, without compromising safety, by modifying "normal" processes. The study objective is to examine escalation policies in theory and practice. This was a mixed-method study involving a conceptual analysis of National Health Service escalation policies (n=12) and associated escalation actions (n=92), as well as a detailed ethnographic study of escalation in situ during a 16-month period in a large UK ED (n=30 observations). The conceptual analysis of National Health Service escalation policies found that their use requires the ability to dynamically reconfigure resources (staff and equipment), change work flow, and relocate patients. In practice, it was discovered that when the ED is under pressure, these prerequisites cannot always be attained. Instead, escalation processes were adapted to manage pressures informally. This adaptive need ("work as done") was found to be incompletely specified in policies ("work as imagined"). Formal escalation actions and their implementation in practice differed and varied in their effectiveness. Monitoring how escalation works in practice is essential in understanding whether and how escalation policies help to manage workload. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Characterization and compensation of the residual chirp in a Mach-Zehnder-type electro-optical intensity modulator.

PubMed

Rogers, C E; Carini, J L; Pechkis, J A; Gould, P L

2010-01-18

We utilize various techniques to characterize the residual phase modulation of a waveguide-based Mach-Zehnder electro-optical intensity modulator. A heterodyne technique is used to directly measure the phase change due to a given change in intensity, thereby determining the chirp parameter of the device. This chirp parameter is also measured by examining the ratio of sidebands for sinusoidal amplitude modulation. Finally, the frequency chirp caused by an intensity pulse on the nanosecond time scale is measured via the heterodyne signal. We show that this chirp can be largely compensated with a separate phase modulator. The various measurements of the chirp parameter are in reasonable agreement.

From headache to tumour: An examination of health anxiety, health-related Internet use and 'query escalation'.

PubMed

Singh, Karmpaul; Brown, Richard J

2016-09-01

The current study aimed to explore the phenomenon of disease-related 'query escalation' in high/low health anxious Internet users (N = 40). During a 15-minute health-related Internet search, participants rated their anxiety and the perceived seriousness of information on each page. Post-search interviews determined the reasons for, and effects of, escalating queries to consider serious diseases. Both groups were found to be significantly more anxious after escalating queries. The high group was significantly more likely to escalate queries. Evaluating personal relevance of material was the main reason for escalations and moderated anxiety post-escalation. We conclude that searching for online disease information can increase anxiety, particularly for people worried about their health. © The Author(s) 2015.

A comparative study of standard intensity-modulated radiotherapy and RapidArc planning techniques for ipsilateral and bilateral head and neck irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pursley, Jennifer, E-mail: jpursley@mgh.harvard.edu; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Damato, Antonio L.

The purpose of this study was to investigate class solutions using RapidArc volumetric-modulated arc therapy (VMAT) planning for ipsilateral and bilateral head and neck (H&N) irradiation, and to compare dosimetric results with intensity-modulated radiotherapy (IMRT) plans. A total of 14 patients who received ipsilateral and 10 patients who received bilateral head and neck irradiation were retrospectively replanned with several volumetric-modulated arc therapy techniques. For ipsilateral neck irradiation, the volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the contralateral parotid, two 260° or 270° arcs, and two 210° arcs. For bilateral neck irradiation, themore » volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the shoulders, and 3 arcs. All patients had a sliding-window-delivery intensity-modulated radiotherapy plan that was used as the benchmark for dosimetric comparison. For ipsilateral neck irradiation, a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid was dosimetrically comparable to intensity-modulated radiotherapy, with improved conformity (conformity index = 1.22 vs 1.36, p < 0.04) and lower contralateral parotid mean dose (5.6 vs 6.8 Gy, p < 0.03). For bilateral neck irradiation, 3-arc volumetric-modulated arc therapy techniques were dosimetrically comparable to intensity-modulated radiotherapy while also avoiding irradiation through the shoulders. All volumetric-modulated arc therapy techniques required fewer monitor units than sliding-window intensity-modulated radiotherapy to deliver treatment, with an average reduction of 35% for ipsilateral plans and 67% for bilateral plans. Thus, for ipsilateral head and neck irradiation a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid is recommended. For bilateral neck irradiation, 2- or 3-arc techniques are dosimetrically comparable to intensity-modulated radiotherapy, but more work is needed to determine the optimal approaches by disease site.« less

A comparative study of standard intensity-modulated radiotherapy and RapidArc planning techniques for ipsilateral and bilateral head and neck irradiation.

PubMed

Pursley, Jennifer; Damato, Antonio L; Czerminska, Maria A; Margalit, Danielle N; Sher, David J; Tishler, Roy B

2017-01-01

The purpose of this study was to investigate class solutions using RapidArc volumetric-modulated arc therapy (VMAT) planning for ipsilateral and bilateral head and neck (H&N) irradiation, and to compare dosimetric results with intensity-modulated radiotherapy (IMRT) plans. A total of 14 patients who received ipsilateral and 10 patients who received bilateral head and neck irradiation were retrospectively replanned with several volumetric-modulated arc therapy techniques. For ipsilateral neck irradiation, the volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the contralateral parotid, two 260° or 270° arcs, and two 210° arcs. For bilateral neck irradiation, the volumetric-modulated arc therapy techniques included two 360° arcs, two 360° arcs with avoidance sectors around the shoulders, and 3 arcs. All patients had a sliding-window-delivery intensity-modulated radiotherapy plan that was used as the benchmark for dosimetric comparison. For ipsilateral neck irradiation, a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid was dosimetrically comparable to intensity-modulated radiotherapy, with improved conformity (conformity index = 1.22 vs 1.36, p < 0.04) and lower contralateral parotid mean dose (5.6 vs 6.8Gy, p < 0.03). For bilateral neck irradiation, 3-arc volumetric-modulated arc therapy techniques were dosimetrically comparable to intensity-modulated radiotherapy while also avoiding irradiation through the shoulders. All volumetric-modulated arc therapy techniques required fewer monitor units than sliding-window intensity-modulated radiotherapy to deliver treatment, with an average reduction of 35% for ipsilateral plans and 67% for bilateral plans. Thus, for ipsilateral head and neck irradiation a volumetric-modulated arc therapy technique using two 360° arcs with avoidance sectors around the contralateral parotid is recommended. For bilateral neck irradiation, 2- or 3-arc techniques are dosimetrically comparable to intensity-modulated radiotherapy, but more work is needed to determine the optimal approaches by disease site. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Prostate Dose Escalation by Innovative Inverse Planning-Driven IMRT

DTIC Science & Technology

2006-11-01

fLJ and at each step, we find the minimizer u,\\ of J’. The Euler-Lagrange equation for the regularized J’ functional is u- div ( 1 Vu )= f E S1,2A...GD, Agazaryan N, Solberg TD . 2003. The effects of tumor motion on planning and delivery of respiratory-gated IMRT. Med Phys 30:1052-1066. Jaffray DA...modulated) radiation therapy: a review. Phys Med Biol 51 :R403-425. Wink NM, McNitt-Gray MF, Solberg TD . 2005. Optimization of multi-slice helical

Simultaneous Integrated Boost–Intensity Modulated Radiation Therapy With Concomitant Capecitabine and Mitomycin C for Locally Advanced Anal Carcinoma: A Phase 1 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deenen, Maarten J.; Dewit, Luc; Boot, Henk

2013-04-01

Purpose: Newer radiation techniques, and the application of continuous 5-FU exposure during radiation therapy using oral capecitabine may improve the treatment of anal cancer. This phase 1, dose-finding study assessed the feasibility and efficacy of simultaneous integrated boost–intensity modulated radiation therapy (SIB-IMRT) with concomitant capecitabine and mitomycin C in locally advanced anal cancer, including pharmacokinetic and pharmacogenetic analyses. Methods and Materials: Patients with locally advanced anal carcinoma were treated with SIB-IMRT in 33 daily fractions of 1.8 Gy to the primary tumor and macroscopically involved lymph nodes and 33 fractions of 1.5 Gy electively to the bilateral iliac and inguinalmore » lymph node areas. Patients received a sequential radiation boost dose of 3 × 1.8 Gy on macroscopic residual tumor if this was still present in week 5 of treatment. Mitomycin C 10 mg/m{sup 2} (maximum 15 mg) was administered intravenously on day 1, and capecitabine was given orally in a dose-escalated fashion (500-825 mg/m{sup 2} b.i.d.) on irradiation days, until dose-limiting toxicity emerged in ≥2 of maximally 6 patients. An additional 8 patients were treated at the maximum tolerated dose (MTD). Results: A total of 18 patients were included. The MTD of capecitabine was determined to be 825 mg/m{sup 2} b.i.d. The predominant acute grade ≥3 toxicities included radiation dermatitis (50%), fatigue (22%), and pain (6%). Fifteen patients (83% [95%-CI: 66%-101%]) achieved a complete response, and 3 (17%) patients a partial response. With a median follow-up of 28 months, none of the complete responders, and 2 partial responders had relapsed. Conclusions: SIB-IMRT with concomitant single dose mitomycin C and capecitabine 825 mg/m{sup 2} b.i.d. on irradiation days resulted in an acceptable safety profile, and proved to be a tolerable and effective treatment regimen for locally advanced anal cancer.« less

Dosimetric Predictors of Duodenal Toxicity After Intensity Modulated Radiation Therapy for Treatment of the Para-aortic Nodes in Gynecologic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verma, Jonathan; Sulman, Erik P.; Jhingran, Anuja

Purpose: To determine the incidence of duodenal toxicity in patients receiving intensity modulated radiation therapy (IMRT) for treatment of para-aortic nodes and to identify dosimetric parameters predictive of late duodenal toxicity. Methods and Materials: We identified 105 eligible patients with gynecologic malignancies who were treated with IMRT for gross metastatic disease in the para-aortic nodes from January 1, 2005, through December 31, 2009. Patients were treated to a nodal clinical target volume to 45 to 50.4 Gy with a boost to 60 to 66 Gy. The duodenum was contoured, and dosimetric data were exported for analysis. Duodenal toxicity was scoredmore » according to Radiation Therapy Oncology Group criteria. Univariate Cox proportional hazards analysis and recursive partitioning analysis were used to determine associations between dosimetric variables and time to toxicity and to identify the optimal threshold that separated patients according to risk of toxicity. Results: Nine of the 105 patients experienced grade 2 to grade 5 duodenal toxicity, confirmed by endoscopy in all cases. The 3-year actuarial rate of any duodenal toxicity was 11.7%. A larger volume of the duodenum receiving 55 Gy (V55) was associated with higher rates of duodenal toxicity. The 3-year actuarial rates of duodenal toxicity with V55 above and below 15 cm{sup 3} were 48.6% and 7.4%, respectively (P<.01). In Cox univariate analysis of dosimetric variables, V55 was associated with duodenal toxicity (P=.029). In recursive partitioning analysis, V55 less than 13.94% segregated all patients with duodenal toxicity. Conclusions: Dose-escalated IMRT can safely and effectively treat para-aortic nodal disease in gynecologic malignancies, provided that care is taken to limit the dose to the duodenum to reduce the risk of late duodenal toxicity. Limiting V55 to below 15 cm{sup 3} may reduce the risk of duodenal complications. In cases where the treatment cannot be delivered within these constraints, consideration should be given to other treatment approaches such as resection or initial chemotherapy.« less

Temporary organ displacement coupled with image-guided, intensity-modulated radiotherapy for paraspinal tumors

PubMed Central

2013-01-01

Background To investigate the feasibility and dosimetric improvements of a novel technique to temporarily displace critical structures in the pelvis and abdomen from tumor during high-dose radiotherapy. Methods Between 2010 and 2012, 11 patients received high-dose image-guided intensity-modulated radiotherapy with temporary organ displacement (TOD) at our institution. In all cases, imaging revealed tumor abutting critical structures. An all-purpose drainage catheter was introduced between the gross tumor volume (GTV) and critical organs at risk (OAR) and infused with normal saline (NS) containing 5-10% iohexol. Radiation planning was performed with the displaced OARs and positional reproducibility was confirmed with cone-beam CT (CBCT). Patients were treated within 36 hours of catheter placement. Radiation plans were re-optimized using pre-TOD OARs to the same prescription and dosimetrically compared with post-TOD plans. A two-tailed permutation test was performed on each dosimetric measure. Results The bowel/rectum was displaced in six patients and kidney in four patients. One patient was excluded due to poor visualization of the OAR; thus 10 patients were analyzed. A mean of 229 ml (range, 80–1000) of NS 5-10% iohexol infusion resulted in OAR mean displacement of 17.5 mm (range, 7–32). The median dose prescribed was 2400 cGy in one fraction (range, 2100–3000 in 3 fractions). The mean GTV Dmin and PTV Dmin pre- and post-bowel TOD IG-IMRT dosimetry significantly increased from 1473 cGy to 2086 cGy (p=0.015) and 714 cGy to 1214 cGy (p=0.021), respectively. TOD increased mean PTV D95 by 27.14% of prescription (p=0.014) while the PTV D05 decreased by 9.2% (p=0.011). TOD of the bowel resulted in a 39% decrease in mean bowel Dmax (p=0.008) confirmed by CBCT. TOD of the kidney significantly decreased mean kidney dose and Dmax by 25% (0.022). Conclusions TOD was well tolerated, reproducible, and facilitated dose escalation to previously radioresistant tumors abutting critical structures while minimizing dose to OARs. PMID:23800073

Intensity-modulated versus 3-dimensional conformal radiotherapy in the definitive treatment of esophageal cancer: comparison of outcomes and acute toxicity.

PubMed

Haefner, Matthias Felix; Lang, Kristin; Verma, Vivek; Koerber, Stefan Alexander; Uhlmann, Lorenz; Debus, Juergen; Sterzing, Florian

2017-08-15

Though the vast majority of seminal trials for locally advanced esophageal cancer (EC) utilized three-dimensional conformal radiotherapy (3DCRT), the advanced and highly conformal technology known as intensity-modulated radiotherapy (IMRT) can decrease doses to critical cardiopulmonary organs. To date, there have been no studies comparing both modalities as part of definitive chemoradiation (dCRT) for EC. Herein, we investigated local control and survival and evaluated clinical factors associated with these endpoints between cohorts. We retrospectively analyzed 93 patients (3DCRT n = 49, IMRT n = 44) who received dCRT at our institution between 2000 and 2012 with the histologic diagnosis of nonmetastatic EC, a Karnofsky performance status of ≥70, curative treatment intent, and receipt of concomitant CRT. Patients were excluded if receiving <50 Gy. Kaplan-Meier analysis was used to evaluate the endpoints of local relapse rate (LR), progression-free survival (PFS), and overall survival (OS). Cox proportional hazards modeling addressed factors associated with outcomes with univariate and multivariate approaches. Rates of acute toxicities and basic dosimetric parameters were compared between 3DCRT and IMRT patients. Mean follow-up was 34.7 months. The 3-year LR was 28.6% in the 3DCRT group and 22.7% in the IMRT group (p = 0.620). Median PFS were 13.8 and 16.6 months, respectively (p = 0.448). Median OS were 18.4 and 42.0 months, respectively (p = 0.198). On univariate analysis, only cumulative radiation dose was associated with superior LR (hazard ratio (HR) 0.736; 95% confidence interval (CI) 0.635 - 0.916, p = 0.004). Factors clearly affecting survival were not observed. When comparing 3DCRT- versus IMRT-based dCRT, no survival benefits were observed. However, we found a lower local recurrence rate in the IMRT group potentially owing to dose-escalation. Prospective data are needed to verify the presented results herein.

Dosimetric comparison of standard three-dimensional conformal radiotherapy followed by intensity-modulated radiotherapy boost schedule (sequential IMRT plan) with simultaneous integrated boost–IMRT (SIB IMRT) treatment plan in patients with localized carcinoma prostate

PubMed Central

Bansal, A.; Kapoor, R.; Singh, S. K.; Kumar, N.; Oinam, A. S.; Sharma, S. C.

2012-01-01

Aims: Dosimeteric and radiobiological comparison of two radiation schedules in localized carcinoma prostate: Standard Three-Dimensional Conformal Radiotherapy (3DCRT) followed by Intensity Modulated Radiotherapy (IMRT) boost (sequential-IMRT) with Simultaneous Integrated Boost IMRT (SIB-IMRT). Material and Methods: Thirty patients were enrolled. In all, the target consisted of PTV P + SV (Prostate and seminal vesicles) and PTV LN (lymph nodes) where PTV refers to planning target volume and the critical structures included: bladder, rectum and small bowel. All patients were treated with sequential-IMRT plan, but for dosimetric comparison, SIB-IMRT plan was also created. The prescription dose to PTV P + SV was 74 Gy in both strategies but with different dose per fraction, however, the dose to PTV LN was 50 Gy delivered in 25 fractions over 5 weeks for sequential-IMRT and 54 Gy delivered in 27 fractions over 5.5 weeks for SIB-IMRT. The treatment plans were compared in terms of dose–volume histograms. Also, Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) obtained with the two plans were compared. Results: The volume of rectum receiving 70 Gy or more (V > 70 Gy) was reduced to 18.23% with SIB-IMRT from 22.81% with sequential-IMRT. SIB-IMRT reduced the mean doses to both bladder and rectum by 13% and 17%, respectively, as compared to sequential-IMRT. NTCP of 0.86 ± 0.75% and 0.01 ± 0.02% for the bladder, 5.87 ± 2.58% and 4.31 ± 2.61% for the rectum and 8.83 ± 7.08% and 8.25 ± 7.98% for the bowel was seen with sequential-IMRT and SIB-IMRT plans respectively. Conclusions: For equal PTV coverage, SIB-IMRT markedly reduced doses to critical structures, therefore should be considered as the strategy for dose escalation. SIB-IMRT achieves lesser NTCP than sequential-IMRT. PMID:23204659

Maintenance and Safety Practices of Escalator in Commercial Buildings

NASA Astrophysics Data System (ADS)

Afida Isnaini Janipha, Nurul; Nur Aina Syed Alwee, Sharifah; Ariff, Raihan Mohd; Ismail, Faridah

2018-02-01

The escalator is very crucial to transport a person from one place to another. Nevertheless, there are many cases recorded the accidents in relation to escalator. These may occur due to lack of maintenance which leads to systems breakdown, poor safety practices, wear and tear, users’ negligence and others. Thus, proper maintenance systems need to be improvised to prevent and reduce escalator accident in future. This research was aimed to determine the escalator maintenance activities and safety practices in a commercial building. Three case studies were selected within Selangor area. Semi-structured interviews were conducted for collecting data from these three case studies. To achieve the aim of this research, the study was carried out on the maintenance activities, safety practices and cost related to escalator maintenance. As one of the important means of access in building, it is very crucial to increase effectiveness of escalator particularly in commercial building. It is expected that readers will get clear information on the maintenance activities and safety practices of escalator in commercial building.

Impact of a clinical microbiology-intensive care consulting program in a cardiothoracic intensive care unit.

PubMed

Arena, Fabio; Scolletta, Sabino; Marchetti, Luca; Galano, Angelo; Maglioni, Enivarco; Giani, Tommaso; Corsi, Elisabetta; Lombardi, Silvia; Biagioli, Bonizella; Rossolini, Gian Maria

2015-09-01

A preintervention-postintervention study was carried out over a 4-year period to assess the impact of an antimicrobial stewardship intervention, based on clinical microbiologist ward rounds (clinical microbiology-intensive care partnership [CMICP]), at a cardiothoracic intensive care unit. Comparison of clinical data for 37 patients with diagnosis of bacteremia (18 from preintervention period, 19 from postintervention period) revealed that CMICP implementation resulted in (1) significant increase of appropriate empirical treatments (+34%, P = .029), compliance with guidelines (+28%, P = .019), and number of de-escalations (+42%, P = .032); and (2) decrease (average = 2.5 days) in time to optimization of antimicrobial therapy and levofloxacin (Δ 2009-2012 = -74 defined daily dose [DDD]/1,000 bed days) and teicoplanin (Δ 2009-2012 = -28 DDD/1,000 bed days) use. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Helping parents deal with children's acute disciplinary problems without escalation: the principle of nonviolent resistance.

PubMed

Omer, H

2001-01-01

There are two kinds of escalation between parents and children with acute discipline problems: (a) complementary escalation, in which parental giving-in leads to a progressive increase in the child's demands, and (b) reciprocal escalation, in which hostility begets hostility. Extant programs for helping parents deal with children with such problems focus mainly on one kind of escalation to the neglect of the other. The systematic use of Gandhi's principle of "nonviolent resistance" allows for a parental attitude that counters both kinds of escalation. An intervention is described, which allows parents to put this principle into practice.

Escalate shamefully, de-escalate angrily or gratefully: the influence of discrete emotions on escalation of commitment.

PubMed

Dang, Junhua; Xiao, Shanshan; Liljedahl, Sophie

2014-08-01

Decision makers often tend to escalate their commitment when faced with a dilemma of whether to continue a losing course of action. Researchers recently began to investigate the influence of discrete emotions on this decision tendency. However, this work has mainly focused on negative emotions and rarely considered positive emotions, to say nothing of comparing the effects of both of them simultaneously. The current study addresses this need by presenting the results of three experiments that examined the effects of four emotions of both positive and negative valences in escalation situations. Experiment 1 investigated the relationships of three trait emotions (hope, shame, and anger) and escalation of commitment. Experiments 2 and 3 examined the effects of three induced emotions (anger, shame, and gratitude) on escalation of commitment in a student sample and an employee sample, respectively. The results revealed that the effects of discrete emotions in escalation situations are mainly due to their associated differences on the appraisal dimension of responsibility that is related to escalation situations rather than their valence. The theoretical and practical implications are discussed. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) infections: are carbapenem alternatives achievable in daily practice?

PubMed

Pilmis, B; Delory, T; Groh, M; Weiss, E; Emirian, A; Lecuyer, H; Lesprit, P; Zahar, J-R

2015-10-01

To avoid the use of carbapenems, alternatives such as cephamycin, piperacillin-tazobactam, and others are suggested for the treatment of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) infections. The aim of this study was to evaluate the frequency and the feasibility of antimicrobial de-escalation for ESBL-PE-related infections. A prospective observational, bi centric cohort study was conducted. All patients with ESBL-PE infections were included. De-escalation was systematically suggested if patients were clinically stable and the isolate was susceptible to possible alternatives. Seventy-nine patients were included: 36 (45.6%) were children, 27 (34.1%) were hospitalized in intensive care units, and 37 (47%) were immunocompromised. Urinary tract infections, pneumonia, and catheter-related bloodstream infections accounted for 45.6%, 19%, and 10%, respectively, of the cohort. Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae were the three most frequent causative organisms isolated. On day 5, 47 (59.2%) of the patients were still receiving carbapenems. Antimicrobial resistance (44.7%), infection relapse (26.9%), and clinical instability (19.2%) were the most important reasons for not prescribing alternatives. E. coli-related infections appeared to be a protective factor against maintaining the carbapenem prescription (odds ratio 0.11, 95% confidence interval 0.041-0.324; p=0.0013). In clinical practice, less than 50% of patients with ESBL-PE-related infections were de-escalated after empirical treatment with carbapenems. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dosimetric analysis of testicular doses in prostate intensity-modulated and volumetric-modulated arc radiation therapy at different energy levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onal, Cem, E-mail: hcemonal@hotmail.com; Arslan, Gungor; Dolek, Yemliha

2016-01-01

The aim of this study is to evaluate the incidental testicular doses during prostate radiation therapy with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) at different energies. Dosimetric data of 15 patients with intermediate-risk prostate cancer who were treated with radiotherapy were analyzed. The prescribed dose was 78 Gy in 39 fractions. Dosimetric analysis compared testicular doses generated by 7-field intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy with a single arc at 6, 10, and 15 MV energy levels. Testicular doses calculated from the treatment planning system and doses measured from the detectors were analyzed. Mean testicular doses from themore » intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy per fraction calculated in the treatment planning system were 16.3 ± 10.3 cGy vs 21.5 ± 11.2 cGy (p = 0.03) at 6 MV, 13.4 ± 10.4 cGy vs 17.8 ± 10.7 cGy (p = 0.04) at 10 MV, and 10.6 ± 8.5 cGy vs 14.5 ± 8.6 cGy (p = 0.03) at 15 MV, respectively. Mean scattered testicular doses in the phantom measurements were 99.5 ± 17.2 cGy, 118.7 ± 16.4 cGy, and 193.9 ± 14.5 cGy at 6, 10, and 15 MV, respectively, in the intensity-modulated radiotherapy plans. In the volumetric-modulated arc radiotherapy plans, corresponding testicular doses per course were 90.4 ± 16.3 cGy, 103.6 ± 16.4 cGy, and 139.3 ± 14.6 cGy at 6, 10, and 15 MV, respectively. In conclusions, this study was the first to measure the incidental testicular doses by intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy plans at different energy levels during prostate-only irradiation. Higher photon energy and volumetric-modulated arc radiotherapy plans resulted in higher incidental testicular doses compared with lower photon energy and intensity-modulated radiotherapy plans.« less

Effective ingredients of verbal de-escalation: validating an English modified version of the 'De-Escalating Aggressive Behaviour Scale'.

PubMed

Mavandadi, V; Bieling, P J; Madsen, V

2016-08-01

WHAT IS KNOWN ON THE SUBJECT?: Verbal de-escalation is an intervention aimed at calmly managing an agitated client to prevent violence. Effective de-escalation can help reduce the use of seclusion and restraint in psychiatric settings. Despite its importance in practice, there is little agreement on the necessary techniques of de-escalation and most of the research on the topic is based on expert opinion. To our knowledge, only one attempt at quantifying de-escalation skill has been pursued through the German-language De-Escalating Aggressive Behaviour Scale (DABS). While the DABS identified seven qualities necessary for de-escalation, it has not been validated in English and may lack important descriptors. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The present study enhanced the original DABS with best, acceptable and least desirable staff de-escalation practice descriptions for each of the seven items. This enhancement of the DABS lead to the creation of the English modified DABS (EMDABS). The EMDABS was psychometrically validated for use in research and practice: raters could use the EMDABS with a high level of agreement and consistency. Also, the scale appeared to measure a single cohesive construct - de-escalation. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: With further validation, the EMDABS has potential to be the first English quantitative measure of de-escalation. The EMDABS offers seven items, with associated best practice descriptions, that may be used to inform de-escalation practice. The EMDABS can be used to evaluate training and education programmes and inform how these programmes and independent de-escalation practice may be improved. Introduction Verbal de-escalation is crucial to a non-coercive psychiatric environment. Despite its importance, the literature on de-escalation is sparse and mostly qualitative. To address this, Nau et al. (2009) quantified de-escalation by creating the German-language De-Escalating Aggressive Behaviour Scale (DABS). The DABS provides seven skills necessary for de-escalation, however it has not been validated in English and lacks the necessary anchor descriptions to make it useful. Aim To modify the DABS to include descriptions of best, acceptable and least desirable staff practice and to validate the English modified DABS (EMDABS). Method To develop item descriptions for the EMDABS, 50 conflictual staff-patient interactions were reviewed, summarized and cross-referenced with the literature (n = 19). Three raters then used the EMDABS to evaluate 272 simulations depicting these interactions. Results The EMDABS demonstrated very good inter-rater reliability [ICC (3, 1) = 0.752] and strong internal consistency (α = 0.901). A factor analysis revealed that the seven items were best represented by a single factor. Discussion The EMDABS was validated for future use in research and practice. Additional validation and future research directions are discussed. Implications for practice The EMDABS holds promise as a quantitative measure of de-escalation. Its seven items and best practice guidelines have clinical implications for improving practice and training. © 2016 John Wiley & Sons Ltd.

Plasma optical modulators for intense lasers

PubMed Central

Yu, Lu-Le; Zhao, Yao; Qian, Lie-Jia; Chen, Min; Weng, Su-Ming; Sheng, Zheng-Ming; Jaroszynski, D. A.; Mori, W. B.; Zhang, Jie

2016-01-01

Optical modulators can have high modulation speed and broad bandwidth, while being compact. However, these optical modulators usually work for low-intensity light beams. Here we present an ultrafast, plasma-based optical modulator, which can directly modulate high-power lasers with intensity up to 1016 W cm−2 to produce an extremely broad spectrum with a fractional bandwidth over 100%, extending to the mid-infrared regime in the low-frequency side. This concept relies on two co-propagating laser pulses in a sub-millimetre-scale underdense plasma, where a drive laser pulse first excites an electron plasma wave in its wake while a following carrier laser pulse is modulated by the plasma wave. The laser and plasma parameters suitable for the modulator to work are based on numerical simulations. PMID:27283369

Method and apparatus of highly linear optical modulation

DOEpatents

DeRose, Christopher; Watts, Michael R.

2016-05-03

In a new optical intensity modulator, a nonlinear change in refractive index is used to balance the nonlinearities in the optical transfer function in a way that leads to highly linear optical intensity modulation.

De-escalating aggression and violence in the mental health setting.

PubMed

Cowin, Leanne; Davies, Rhian; Estall, Graham; Berlin, Theresa; Fitzgerald, Maria; Hoot, Sandra

2003-03-01

Aggressive and violent incidents in the health-care setting are increasing phenomena around the world. The evidence from current literature suggests that changes in health-care access, nursing staff shortages and patient acuity are some of the possible causes. De-escalation is a valuable intervention that can be used by nurses to help counter the growing problems of aggression and violence. The de-escalation project, discussed in the present paper, aimed to explore de-escalation as an important therapeutic process and is an event of considerable potential in the management of aggression and violence. While de-escalation is not a new tool, particularly in the mental health-care setting, an educative programme aimed at renewing nurses' knowledge and skills in de-escalation is a timely project. The final de-escalation kit included a large glossy poster, a nursing staff survey, an in-service education session and a literature-based discussion paper. The de-escalation kit can be of considerable benefit to those nurses who are transient within the workplace, such as casual and agency nurses.

Modeling and Validation of Performance Limitations for the Optimal Design of Interferometric and Intensity-Modulated Fiber Optic Displacement Sensors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moro, Erik A.

Optical fiber sensors offer advantages over traditional electromechanical sensors, making them particularly well-suited for certain measurement applications. Generally speaking, optical fiber sensors respond to a desired measurand through modulation of an optical signal's intensity, phase, or wavelength. Practically, non-contacting fiber optic displacement sensors are limited to intensity-modulated and interferometric (or phase-modulated) methodologies. Intensity-modulated fiber optic displacement sensors relate target displacement to a power measurement. The simplest intensity-modulated sensor architectures are not robust to environmental and hardware fluctuations, since such variability may cause changes in the measured power level that falsely indicate target displacement. Differential intensity-modulated sensors have been implemented, offeringmore » robustness to such intensity fluctuations, and the speed of these sensors is limited only by the combined speed of the photodetection hardware and the data acquisition system (kHz-MHz). The primary disadvantages of intensity-modulated sensing are the relatively low accuracy (?m-mm for low-power sensors) and the lack of robustness, which consequently must be designed, often with great difficulty, into the sensor's architecture. White light interferometric displacement sensors, on the other hand, offer increased accuracy and robustness. Unlike their monochromatic-interferometer counterparts, white light interferometric sensors offer absolute, unambiguous displacement measurements over large displacement ranges (cm for low-power, 5 mW, sources), necessitating no initial calibration, and requiring no environmental or feedback control. The primary disadvantage of white light interferometric displacement sensors is that their utility in dynamic testing scenarios is limited, both by hardware bandwidth and by their inherent high-sensitivity to Doppler-effects. The decision of whether to use either an intensity-modulated interferometric sensor depends on an appropriate performance function (e.g., desired displacement range, accuracy, robustness, etc.). In this dissertation, the performance limitations of a bundled differential intensity-modulated displacement sensor are analyzed, where the bundling configuration has been designed to optimize performance. The performance limitations of a white light Fabry-Perot displacement sensor are also analyzed. Both these sensors are non-contacting, but they have access to different regions of the performance-space. Further, both these sensors have different degrees of sensitivity to experimental uncertainty. Made in conjunction with careful analysis, the decision of which sensor to deploy need not be an uninformed one.« less

Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study.

PubMed

Chen, Jianzhou; Guo, Hong; Zhai, Tiantian; Chang, Daniel; Chen, Zhijian; Huang, Ruihong; Zhang, Wuzhe; Lin, Kun; Guo, Longjia; Zhou, Mingzhen; Li, Dongsheng; Li, Derui; Chen, Chuangzhen

2016-04-19

The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities.

SU-E-T-605: RapidArc Combined with DIBH Technique for Thoracic Esophageal Carcinoma: The Potential Value of Target Immobilization and Reduced Lung Density in Dose Escalation.

PubMed

Yin, Y; Liu, T; Zhai, D

2012-06-01

To compare the dosimetric benefits of Rapidarc (RA) combined with deep inspiration breath-hold (DIBH) with those of other standard techniques, including free breathing (FB) during fixed-field intensity modulated radiation therapy (IMRT) and dual arc RA, in the treatment of patients with thoracic esophageal carcinoma (EC). Ten patients with EC underwent computed tomography (CT) scans under 2 respiration conditions: free-breathing (FB) and DIBH. These scans were used to generate 3-dimensional conformal treatment plans. For breath-hold scans, the patients were brought to reproducible respiration levels using active breathing control (ABC) maneuvers. Planning target volumes (PTVs) for FB plans included a 0.5 cm margin for setup plus a 1 cm margin equal to the extent of tumor motion for respiration. PTVs for DIBH plans included a 0.5 cm margin for setup error and a 0.5 cm margin for residual uncertainty in tumor position. Using a dose level of 60 Gy to the PTV, three treatment plans were generated: IMRT-FB, RA-FB and RA-ABC, and the target and normal tissue volumes were compared, as were the dosimetry parameters. On average, the DIBH technique resulted in increased lung volumes compared with FB techniques. There was no significant differences in gross tumor volume between the two breathing states (p > 0.05); but PTV and heart volume were larger for FB than for DIBH (p < 0.05). The overall CI and HI for the RA-ABC plan was slightly inferior to those of the IMRT- FB and RA-FB plans (p < 0.05 each). With DIBH, the heart was partly out of the beam portals and the average mean heart dose was reduced. Compared with conventional FB, RA combined with DIBH significantly reduced cardiac and pulmonary doses without compromising the target coverage and may reduce treatment toxicity, enabling dose escalation in future prospective studies of patients with EC. © 2012 American Association of Physicists in Medicine.

Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kountouri, Melpomeni; Zilli, Thomas; Rouzaud, Michel

2016-02-01

Purpose: This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. Methods and Materials: 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities weremore » scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. Results: There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). Conclusions: A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control.« less

De-Escalation of Antibiotics Does Not Increase Mortality in Critically Ill Surgical Patients.

PubMed

Turza, Kristin C; Politano, Amani D; Rosenberger, Laura H; Riccio, Lin M; McLeod, Matthew; Sawyer, Robert G

2016-02-01

Overuse of broad-spectrum antibiotics results in microbial resistance and financially is a healthcare burden. Antibiotic de-escalation refers to starting treatment of a presumed infection with broad-spectrum antibiotics and narrowing drug spectrum based on culture sensitivities. A study was designed to evaluate antibiotic de-escalation at a tertiary care center. We hypothesized that antibiotic de-escalation would not be associated with increased patient mortality rates or worsening of the primary infection. All infections treated in a single, tertiary care Surgical ICU between August 2009 and December 2011 were reviewed. Antibiotic treatment was classified by skilled reviewers as being either de-escalated or not. Outcomes were evaluated. Univariate statistics were performed (Fisher exact test, Chi-square for categorical data; student t-test for continuous variables). Multivariable logistic regression was completed. A total of 2,658 infections were identified. De-escalation was identified for 995 infections and non-deescalation occurred in 1,663. Patients were similar in age (de-escalated 55 ± 16 y vs. 56 ± 16, p = 0.1) and gender (de-escalated 60% males vs. 58%, p = 0.4). There were substantially greater APACHE II scores in non-deescalated patients (15 ± 8 vs. 14 ± 8, p = 0.03). A greater mortality rate among patients with infections treated without de-escalation was observed compared with those treated with de-escalation (9% vs. 6%, p = 0.002). Total antibiotic duration was substantially longer in the de-escalated group (15 ± 13 d vs. 13 ± 13, p = 0.0001). Multivariable analysis found that de-escalation decreased mortality rates (OR = 0.69; 95%CI, 0.49-0.97; p = 0.04) and high APACHE II score independently increased mortality rates (OR = 1.2; 95%CI, 1.1-1.2; p = 0.0001). Other parameters included were age and infection site. Antibiotic de-escalation was not associated with increased mortality rates, but the duration of antibiotic use was longer in this group. Greater mortality rates were observed in the non-deescalated group, but this likely owes at least in part to their relatively greater severity of disease classification (APACHE II). Further investigation will help evaluate whether antibiotic de-escalation will improve the quality of patient care.

Male Weaponry in a Fighting Cricket

PubMed Central

Judge, Kevin A.; Bonanno, Vanessa L.

2008-01-01

Sexually selected male weaponry is widespread in nature. Despite being model systems for the study of male aggression in Western science and for cricket fights in Chinese culture, field crickets (Orthoptera, Gryllidae, Gryllinae) are not known to possess sexually dimorphic weaponry. In a wild population of the fall field cricket, Gryllus pennsylvanicus, we report sexual dimorphism in head size as well as the size of mouthparts, both of which are used when aggressive contests between males escalate to physical combat. Male G. pennsylvanicus have larger heads, maxillae and mandibles than females when controlling for pronotum length. We conducted two experiments to test the hypothesis that relatively larger weaponry conveys an advantage to males in aggressive contests. Pairs of males were selected for differences in head size and consequently were different in the size of maxillae and mandibles. In the first experiment, males were closely matched for body size (pronotum length), and in the second, they were matched for body mass. Males with proportionately larger weaponry won more fights and increasing differences in weaponry size between males increased the fighting success of the male with the larger weaponry. This was particularly true when contests escalated to grappling, the most intense level of aggression. However, neither contest duration nor intensity was related to weaponry size as predicted by models of contest settlement. These results are the first evidence that the size of the head capsule and mouthparts are under positive selection via male-male competition in field crickets, and validate 800-year-old Chinese traditional knowledge. PMID:19107188

Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study.

PubMed

Shehabi, Yahya; Bellomo, Rinaldo; Kadiman, Suhaini; Ti, Lian Kah; Howe, Belinda; Reade, Michael C; Khoo, Tien Meng; Alias, Anita; Wong, Yu-Lin; Mukhopadhyay, Amartya; McArthur, Colin; Seppelt, Ian; Webb, Steven A; Green, Maja; Bailey, Michael J

2018-06-01

In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Harmonized data from prospective multicenter international longitudinal cohort studies SETTING:: Diverse mix of ICUs. Critically ill patients expected to be ventilated for longer than 24 hours. Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (SD) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47-8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15-1.46]; p < 0.001, delirium hazard ratio [95% CI], 1.25 [1.10-1.43]), p value equals to 0.001 and reduced chance of early extubation hazard ratio (95% CI) 0.80 (0.73-0.87), p value of less than 0.001. Agitation level independently predicted subsequent delirium hazard ratio [95% CI], of 1.25 (1.04-1.49), p value equals to 0.02. Delirium or mobilization episodes within 168 hours, adjusted for sedation intensity, were not associated with survival. Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation. These observations suggest that keeping sedation level equivalent to a Richmond Agitation Sedation Scale 0 is a clinically desirable goal.

Interactive Book Reading to Accelerate Word Learning by Kindergarten Children With Specific Language Impairment: Identifying an Adequate Intensity and Variation in Treatment Response.

PubMed

Storkel, Holly L; Voelmle, Krista; Fierro, Veronica; Flake, Kelsey; Fleming, Kandace K; Romine, Rebecca Swinburne

2017-01-01

This study sought to identify an adequate intensity of interactive book reading for new word learning by children with specific language impairment (SLI) and to examine variability in treatment response. An escalation design adapted from nontoxic drug trials (Hunsberger, Rubinstein, Dancey, & Korn, 2005) was used in this Phase I/II preliminary clinical trial. A total of 27 kindergarten children with SLI were randomized to 1 of 4 intensities of interactive book reading: 12, 24, 36, or 48 exposures. Word learning was monitored through a definition task and a naming task. An intensity response curve was examined to identify the adequate intensity. Correlations and classification accuracy were used to examine variation in response to treatment relative to pretreatment and early treatment measures. Response to treatment improved as intensity increased from 12 to 24 to 36 exposures, and then no further improvements were observed as intensity increased to 48 exposures. There was variability in treatment response: Children with poor phonological awareness, low vocabulary, and/or poor nonword repetition were less likely to respond to treatment. The adequate intensity for this version of interactive book reading was 36 exposures, but further development of the treatment is needed to increase the benefit for children with SLI.

Interactive Book Reading to Accelerate Word Learning by Kindergarten Children With Specific Language Impairment: Identifying an Adequate Intensity and Variation in Treatment Response

PubMed Central

Voelmle, Krista; Fierro, Veronica; Flake, Kelsey; Fleming, Kandace K.; Romine, Rebecca Swinburne

2017-01-01

Purpose This study sought to identify an adequate intensity of interactive book reading for new word learning by children with specific language impairment (SLI) and to examine variability in treatment response. Method An escalation design adapted from nontoxic drug trials (Hunsberger, Rubinstein, Dancey, & Korn, 2005) was used in this Phase I/II preliminary clinical trial. A total of 27 kindergarten children with SLI were randomized to 1 of 4 intensities of interactive book reading: 12, 24, 36, or 48 exposures. Word learning was monitored through a definition task and a naming task. An intensity response curve was examined to identify the adequate intensity. Correlations and classification accuracy were used to examine variation in response to treatment relative to pretreatment and early treatment measures. Results Response to treatment improved as intensity increased from 12 to 24 to 36 exposures, and then no further improvements were observed as intensity increased to 48 exposures. There was variability in treatment response: Children with poor phonological awareness, low vocabulary, and/or poor nonword repetition were less likely to respond to treatment. Conclusion The adequate intensity for this version of interactive book reading was 36 exposures, but further development of the treatment is needed to increase the benefit for children with SLI. PMID:28036410

Intensity-based fibre-optic sensing system using contrast modulation of subcarrier interference pattern

NASA Technical Reports Server (NTRS)

Adamovsky, G.; Sherer, T. N.; Maitland, D. J.

1989-01-01

A novel technique to compensate for unwanted intensity losses in a fiber-optic sensing system is described. The technique involves a continuous sinusoidal modulation of the light source intensity at radio frequencies and an intensity sensor placed in an unbalanced interferometer. The system shows high sensitivity and stability.

Raynaud, digital ulcers and calcinosis in scleroderma.

PubMed

Nitsche, Alejandro

2012-01-01

Raynaud, digital ulcers and calcinosis are frequent manifestations of patients with systemic sclerosis. Digital ulcers are seen in more than half of the patients with scleroderma. Hospitalizations, ischemic complications and impairment of hand function are frequently observed in patients with digital ulcers, especially if treatment is delayed. Rapid and intensive treatment escalation in patients with scleroderma and refractory Raynaud's phenomenon is one of the most effective preventive action available in order to avoid the development of digital ulcers and tissue loss. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Development of an antibiotic spectrum score based on veterans affairs culture and susceptibility data for the purpose of measuring antibiotic de-escalation: a modified Delphi approach.

PubMed

Madaras-Kelly, Karl; Jones, Makoto; Remington, Richard; Hill, Nicole; Huttner, Benedikt; Samore, Matthew

2014-09-01

Development of a numerical score to measure the microbial spectrum of antibiotic regimens (spectrum score) and method to identify antibiotic de-escalation events based on application of the score. Web-based modified Delphi method. Physician and pharmacist antimicrobial stewards practicing in the United States recruited through infectious diseases-focused listservs. Three Delphi rounds investigated: organisms and antibiotics to include in the spectrum score, operationalization of rules for the score, and de-escalation measurement. A 4-point ordinal scale was used to score antibiotic susceptibility for organism-antibiotic domain pairs. Antibiotic regimen scores, which represented combined activity of antibiotics in a regimen across all organism domains, were used to compare antibiotic spectrum administered early (day 2) and later (day 4) in therapy. Changes in spectrum score were calculated and compared with Delphi participants' judgments on de-escalation with 20 antibiotic regimen vignettes and with non-Delphi steward judgments on de-escalation of 300 pneumonia regimen vignettes. Method sensitivity and specificity to predict expert de-escalation status were calculated. Twenty-four participants completed all Delphi rounds. Expert support for concepts utilized in metric development was identified. For vignettes presented in the Delphi, the sign of change in score correctly classified de-escalation in all vignettes except those involving substitution of oral antibiotics. The sensitivity and specificity of the method to identify de-escalation events as judged by non-Delphi stewards were 86.3% and 96.0%, respectively. Identification of de-escalation events based on an algorithm that measures microbial spectrum of antibiotic regimens generally agreed with steward judgments of de-escalation status.

[Clinical experience of carbon ion radiotherapy for malignant tumors].

PubMed

Ishikawa, Hitoshi; Tsuji, Hiroshi; Tsujii, Hirohiko

2006-04-01

The carbon ion (C-ion) beams provide unique advantageous biological and physical properties in radiotherapy (RT) for malignant tumors. C-ion beams have a high relative biological effectiveness (RBE) resulting from the high linear energy transfer (LET). In terms of their physical characteristics, C-ion beams exhibit a spread-out Bragg peak (SOBP) and make for a better dose distribution of the target volume by specified beam modulations. Between June 1994 and August 2005, a total of 2,371 patients with malignant tumors were registered in phase I/II dose-escalation studies and clinical phase II trials using C-ion beams generated at Heavy Ion Medical Accelerator in Chiba (HIMAC). In the initial dose-escalation studies, grade 3 or more late rectal complications had developed in some patients. However, the adverse effects were resolved because of the use of appropriate dose levels and modification of the radiation technique. C-ion beams can carry out hypofractionated radiotherapy with a large fraction dose and reduce the overall treatment times compared with conventional radiotherapy. They can also achieve better local tumor control even for radio-resistant tumors such as malignant melanoma, hepatocellular carcinoma and bone and soft tissue sarcomas with minimal morbidity to the normal surrounding tissues.

Optical levitation measurements with intensity-modulated light beams.

PubMed

Cai, W; Li, F; Sun, S; Wang, Y

1997-10-20

Illumination of an optically levitated particle with an intensity-modulated transverse beam induces a transverse vibration of a particle in an optical trap. Based on this, the trapping force of a trap can be measured. Using an intensity-modulated longitudinal levitating beam causes a particle to move vertically, allowing for the determination of some aerodynamic parameters of a particle in air. The principles and the experimental phenomena are described and the initial results are given.

Late recurrence of nonseminomatous germ cell tumor successfully treated with intensity-modulated radiation therapy.

PubMed

Kita, Yuki; Imamura, Masaaki; Mizowaki, Takashi; Norihisa, Yoshiki; Yoshimura, Koji; Hiraoka, Masahiro; Ogawa, Osamu

2013-08-01

We report the case of a 41-year-old man with a late recurrence of nonseminomatous germ cell tumor, which was successfully treated with intensity-modulated radiation therapy. For the residual retrocrural tumor invading the 11th and 12th thoracic vertebrae with an abnormal level of tumor marker (α-fetoprotein: 23.2 ng/ml) after salvage chemotherapy, chemotherapy could not be continued due to its neurotoxicity, and surgery could not be performed due to the location. In this situation, intensity-modulated radiation therapy achieved a complete response of tumor marker. The patient remained in complete clinical remission after 3 years. The efficacy of radiotherapy, especially intensity-modulated radiation therapy, for a nonseminomatous germ cell tumor is discussed.

Regarding the Focal Treatment of Prostate Cancer: Inference of the Gleason Grade From Magnetic Resonance Spectroscopic Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brame, Ryan S.; Zaider, Marco; Zakian, Kristen L.

2009-05-01

Purpose: To quantify, as a function of average magnetic resonance spectroscopy (MRS) score and tumor volume, the probability that a cancer-suspected lesion has an elevated Gleason grade. Methods and Materials: The data consist of MRS imaging ratios R stratified by patient, lesion (contiguous abnormal voxels), voxels, biopsy and pathologic Gleason grade, and lesion volume. The data were analyzed using a logistic model. Results: For both low and high Gleason score biopsy lesions, the probability of pathologic Gleason score {>=}4+3 increases with lesion volume. At low values of R a lesion volume of at least 15-20 voxels is needed to reachmore » a probability of success of 80%; the biopsy result helps reduce the prediction uncertainty. At larger MRS ratios (R > 6) the biopsy result becomes essentially uninformative once the lesion volume is >12 voxels. With the exception of low values of R, for lesions with low Gleason score at biopsy, the MRS ratios serve primarily as a selection tool for assessing lesion volumes. Conclusions: In patients with biopsy Gleason score {>=}4+3, high MRS imaging tumor volume and (creatine + choline)/citrate ratio may justify the initiation of voxel-specific dose escalation. This is an example of biologically motivated focal treatment for which intensity-modulated radiotherapy and especially brachytherapy are ideally suited.« less

Coordinated Recruitment of Cortical-Subcortical Circuits and Ascending Dopamine and Serotonin Neurons During Inhibitory Control of Cocaine Seeking in Rats.

PubMed

Navailles, Sylvia; Guillem, Karine; Vouillac-Mendoza, Caroline; Ahmed, Serge H

2015-09-01

People with cocaine addiction retain some degree of prefrontal cortex (PFC) inhibitory control of cocaine craving, a brain capacity that may underlie the efficacy of cognitive behavioral therapy for addiction. Similar findings were recently found in rats after extended access to and escalation of cocaine self-administration. Rats' inhibitory control of cocaine seeking was flexible, sufficiently strong to suppress cocaine-primed reinstatement and depended, at least in part, on neuronal activity within the prelimbic (PL) PFC. Here, we used a large-scale and high-resolution Fos mapping approach to identify, beyond the PL PFC, how top-down and/or bottom-up PFC-subcortical circuits are recruited during inhibition of cocaine seeking. Overall, we found that effective inhibitory control of cocaine seeking is associated with the coordinated recruitment of different top-down cortical-striatal circuits originating from different PFC territories, and of different bottom-up dopamine (DA) and serotonin (5-HT) midbrain subsystems that normally modulate activity in these circuits. This integrated brain response suggests that rats concomitantly engage and experience intricate cognitive and affective processes when they have to inhibit intense cocaine seeking. Thus, even after extended drug use, rats can be successfully trained to engage whole-brain inhibitory control mechanisms to suppress cocaine seeking. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Randomized CRM: An Approach to Overcoming the Long-Memory Property of the CRM

PubMed Central

Koopmeiners, Joseph S.; Wey, Andrew

2017-01-01

The primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose-finding. Recently, it was shown that the CRM has a tendency to get “stuck” on a dose-level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalation into the standard CRM dose-finding algorithm, as well as a hybrid approach that incorporates escalation and de-escalation only when certain criteria are met. Our simulation results show that both the rCRM and the hybrid approach reduce the trial-to-trial variability in the number of cohorts treated at the MTD but that the hybrid approach has a more favorable trade-off with respect to the average number treated at the MTD. PMID:28340333

The Randomized CRM: An Approach to Overcoming the Long-Memory Property of the CRM.

PubMed

Koopmeiners, Joseph S; Wey, Andrew

2017-01-01

The primary object of a Phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose finding. Recently, it was shown that the CRM has a tendency to get "stuck" on a dose level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalation into the standard CRM dose-finding algorithm, as well as a hybrid approach that incorporates escalation and de-escalation only when certain criteria are met. Our simulation results show that both the rCRM and the hybrid approach reduce the trial-to-trial variability in the number of cohorts treated at the MTD but that the hybrid approach has a more favorable tradeoff with respect to the average number treated at the MTD.

Escalator design features evaluation

NASA Technical Reports Server (NTRS)

Zimmerman, W. F.; Deshpande, G. K.

1982-01-01

Escalators are available with design features such as dual speed (90 and 120 fpm), mat operation and flat steps. These design features were evaluated based on the impact of each on capital and operating costs, traffic flow, and safety. A human factors engineering model was developed to analyze the need for flat steps at various speeds. Mat operation of escalators was found to be cost effective in terms of energy savings. Dual speed operation of escalators with the higher speed used during peak hours allows for efficient operation. A minimum number of flat steps required as a function of escalator speed was developed to ensure safety for the elderly.

Escalator Design Features Evaluation

DOT National Transportation Integrated Search

1982-05-01

This study provides an evaluation of the effectiveness of several special design features associated with escalators in rail transit systems. The objective of the study was to evaluate the effectiveness of three escalator design features: (1) mat ope...

Generation of ultra-wideband triplet pulses based on four-wave mixing and phase-to-intensity modulation conversion.

PubMed

Li, Wei; Wang, Li Xian; Hofmann, Werner; Zhu, Ning Hua; Bimberg, Dieter

2012-08-27

We propose and demonstrate a novel scheme to generate ultra-wideband (UWB) triplet pulses based on four-wave mixing and phase-to-intensity modulation conversion. First a phase-modulated Gaussian doublet pulse is generated by four-wave mixing in a highly nonlinear fiber. Then an UWB triplet pulse is generated by generating the first-order derivative of the phase-modulated Gaussian doublet pulse using an optical filter serving as a frequency discriminator. By locating the optical signal at the linear slope of the optical filter, the phase modulated Gaussian doublet pulse is converted to an intensity-modulated UWB triplet pulse which well satisfies the Federal Communications Commission spectral mask requirements, even in the extremely power-restricted global positioning system band.

Combined MTOR and autophagy inhibition

PubMed Central

Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O’Dwyer, Peter J; Amaravadi, Ravi K

2014-01-01

The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted. PMID:24991838

Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma.

PubMed

Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O'Dwyer, Peter J; Amaravadi, Ravi K

2014-08-01

The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted.

Escalated conflict in a social hierarchy

PubMed Central

Cant, M.A; English, S; Reeve, H.K; Field, J

2006-01-01

Animals that live in cooperative societies form hierarchies in which dominant individuals reap disproportionate benefits from group cooperation. The stability of these societies requires subordinates to accept their inferior status rather than engage in escalated conflict with dominants over rank. Applying the logic of animal contests to these cases predicts that escalated conflict is more likely where subordinates are reproductively suppressed, where group productivity is high, relatedness is low, and where subordinates are relatively strong. We tested these four predictions in the field on co-foundress associations of the paper wasp Polistes dominulus by inducing contests over dominance rank experimentally. Subordinates with lower levels of ovarian development, and those in larger, more productive groups, were more likely to escalate in conflict with their dominant, as predicted. Neither genetic relatedness nor relative body size had significant effects on the probability of escalation. The original dominant emerged as the winner in all except one escalated contest. The results provide the first evidence that reproductive suppression of subordinates increases the threat of escalated conflict, and hence that reproductive sharing can promote stability of the dominant–subordinate relationship. PMID:17015353

Method and apparatus for determining the coordinates of an object

DOEpatents

Pedersen, Paul S; Sebring, Robert

2003-01-01

A method and apparatus is described for determining the coordinates on the surface of an object which is illuminated by a beam having pixels which have been modulated according to predetermined mathematical relationships with pixel position within the modulator. The reflected illumination is registered by an image sensor at a known location which registers the intensity of the pixels as received. Computations on the intensity, which relate the pixel intensities received to the pixel intensities transmitted at the modulator, yield the proportional loss of intensity and planar position of the originating pixels. The proportional loss and position information can then be utilized within triangulation equations to resolve the coordinates of associated surface locations on the object.

Escalation research: Providing new frontiers for applying behavior analysis to organizational behavior

PubMed Central

Goltz, Sonia M.

2000-01-01

Decision fiascoes such as escalation of commitment, the tendency of decision makers to “throw good money after bad,” can have serious consequences for organizations and are therefore of great interest in applied research. This paper discusses the use of behavior analysis in organizational behavior research on escalation. Among the most significant aspects of behavior-analytic research on escalation is that it has indicated that both the patterns of outcomes that decision makers have experienced for past decisions and the patterns of responses that they make are critical for understanding escalation. This research has also stimulated the refinement of methods by researchers to better assess decision making and the role reinforcement plays in it. Finally, behavior-analytic escalation research has not only indicated the utility of reinforcement principles for predicting more complex human behavior but has also suggested some additional areas for future exploration of decision making using behavior analysis. PMID:22478347

Modeling of Millimeter-Wave Modulation Characteristics of Semiconductor Lasers under Strong Optical Feedback

PubMed Central

Bakry, Ahmed

2014-01-01

This paper presents modeling and simulation on the characteristics of semiconductor laser modulated within a strong optical feedback (OFB-)induced photon-photon resonance over a passband of millimeter (mm) frequencies. Continuous wave (CW) operation of the laser under strong OFB is required to achieve the photon-photon resonance in the mm-wave band. The simulated time-domain characteristics of modulation include the waveforms of the intensity and frequency chirp as well as the associated distortions of the modulated mm-wave signal. The frequency domain characteristics include the intensity modulation (IM) and frequency modulation (FM) responses in addition to the associated relative intensity noise (RIN). The signal characteristics under modulations with both single and two mm-frequencies are considered. The harmonic distortion and the third order intermodulation distortion (IMD3) are examined and the spurious free dynamic range (SFDR) is calculated. PMID:25383381

Correlation between odour concentration and odour intensity from exposure to environmental odour

NASA Astrophysics Data System (ADS)

Yusoff, Syafinah; Qamaruz Zaman, Nastaein

2017-08-01

The encroachment of industries, agricultural activities and husbandries to the community area had been a major concern of late, especially in regards to the escalating reports of odour nuisances. A study was performed with the objective of establishing correlation between odour concentration and odour intensity, as an improved method to determine odour nuisances in the community. Universiti Sains Malaysia Engineering Campus was chosen as the study location, due to its vicinity to several odour sources including paper mill, palm oil mill and poultry farm. The odour survey was based on VDI 3940, to determine the level of odour intensity with the corresponding odour concentration measured using an infield olfactometer. The correlation between both methods shows a significant correlation by using Pearson Correlation with a level of confidence of 99.9 percent. The graph plotted between intensity and concentration shows the R2 value of 0.40 which indicated a good correlation between both methods, despite having a high variance and low in consistency. Therefore, this study concludes that the determination of odour concentration should be complemented with odour intensity in order to recognize the true impact of odour nuisance in a community.

Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group.

PubMed

Borchmann, Peter; Haverkamp, Heinz; Lohri, Andreas; Mey, Ulrich; Kreissl, Stefanie; Greil, Richard; Markova, Jana; Feuring-Buske, Michaela; Meissner, Julia; Dührsen, Ulrich; Ostermann, Helmut; Keller, Ulrich; Maschmeyer, Georg; Kuhnert, Georg; Dietlein, Markus; Kobe, Carsten; Eich, Hans; Baues, Christian; Stein, Harald; Fuchs, Michael; Diehl, Volker; Engert, Andreas

2017-04-01

Advanced stage Hodgkin's lymphoma represents a heterogeneous group of patients with different risk profiles. Data suggests that interim PET assessment during chemotherapy is superior to baseline international prognostic scoring in terms of predicting long-term treatment outcome in patients with Hodgkin's lymphoma. We therefore hypothesised that early interim PET-imaging after two courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) might be suitable for guiding treatment in patients with advanced stage Hodgkin's lymphoma. We aimed to assess whether intensifying standard chemotherapy (BEACOPP escalated ) by adding rituximab would improve progression-free survival in patients with positive PET after two courses of chemotherapy. In this open-label, international, randomised, phase 3 study, we recruited patients aged 18-60 years with newly diagnosed, advanced stage Hodgkin's lymphoma from 160 hospitals and 77 private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. Interim PET-imaging was done after two cycles of BEACOPP escalated and centrally assessed by an expert panel. Patients with a positive PET after 2 cycles of BEACOPP escalated chemotherapy (PET-2) were randomly assigned (1:1) to receive six additional courses of either BEACOPP escalated (BEACOPP escalated group) or BEACOPP escalated plus rituximab (R-BEACOPP escalated group). PET-2 was assessed using a 5-point scale with 18 FDG uptake higher than the mediastinal blood pool (corresponding to Deauville scale 3) defined as positive. BEACOPP escalated was given as previously described; rituximab was given intravenously at a dose of 375 mg/m 2 (maximum total dose 700 mg), the first administration starting 24 h before starting the fourth cycle of BEACOPP escalated (day 0 and day 3 in cycle 4, day 1 in cycles 5-8). Randomisation was done centrally and used the minimisation method including a random component, stratified according to centre, age, stage, international prognostic score, and sex. The primary efficacy endpoint was 5 year progression-free survival, analysed in the intention-to-treat population. We are reporting this second planned interim analysis as the final report of the trial. The trial is registered with ClinicalTrials.gov, number NCT00515554. Between May 14, 2008, and May 31, 2011, we enrolled 1100 patients. 440 patients had a positive PET-2 and were randomly assigned to either the BEACOPP escalated group (n=220) or the R-BEACOPP escalated group (n=220). With a median follow-up of 33 months (IQR 25-42) for progression-free survival, estimated 3 year progression-free survival was 91·4% (95% CI 87·0-95·7) for patients in the BEACOPP escalated group and 93·0% (89·4-96·6) for those in the R-BEACOPP escalated group (difference 1·6%, 95% CI -4·0 to 7·3; log rank p=0·99). Common grade 3-4 adverse events were leucopenia (207 [95%] of 218 patients in the BEACOPP escalated group vs 211 [96%] of 220 patients in the R-BEACOPP escalated group), and severe infections (51 [23%] vs 43 [20%] patients). Based on a futility analysis, the independent data monitoring committee recommended publication of this second planned interim analysis as the final result. Six (3%) of 219 patients in the BEACOPP escalated group and ten (5%) of 220 in the R-BEACOPP escalated group died; fatal treatment-related toxic effects occurred in one (<1%) patient in the BEACOPP escalated group and three (1%) in the R-BEACOPP escalated group, all of them due to infection. The addition of rituximab to BEACOPP escalated did not improve the progression-free survival of PET-2 positive patients with advanced stage Hodgkin's lymphoma. However, progression-free survival for PET-2 positive patients was much better than expected, exceeding even the outcome of PET-2-unselected patients in the previous HD15 trial. Thus, PET-2 cannot identify patients at high-risk for treatment failure in the context of the very effective German Hodgkin Study Group standard treatment for advanced stage Hodgkin's lymphoma. Deutsche Krebshilfe; Swiss State Secretariat for Education, Research and Innovation (SERI); and Roche Pharma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Travelling for treatment; does distance and deprivation affect travel for intensity-modulated radiotherapy in the rural setting for head and neck cancer?

PubMed

Cosway, B; Douglas, L; Armstrong, N; Robson, A

2017-06-01

NHS England has commissioned intensity-modulated radiotherapy for head and neck cancers from Newcastle hospitals for patients in North Cumbria. This study assessed whether travel distances affected the decision to travel to Newcastle (to receive intensity-modulated radiotherapy) or Carlisle (to receive conformal radiotherapy). All patients for whom the multidisciplinary team recommended intensity-modulated radiotherapy between December 2013 and January 2016 were included. Index of multiple deprivation scores and travel distances were calculated. Patients were also asked why they chose their treating centre. Sixty-nine patients were included in this study. There were no significant differences in travel distance (p = 0.53) or index of multiple deprivation scores (p = 0.47) between patients opting for treatment in Carlisle or Newcastle. However, 29 of the 33 patients gave travel distance as their main reason for not travelling for treatment. Quantitatively, travel distance and deprivation does not impact on whether patients accept intensity-modulated radiotherapy. However, patients say distance is a major barrier for access. Future research should explore how to reduce this.

Glutamate input in the dorsal raphe nucleus as a determinant of escalated aggression in male mice.

PubMed

Takahashi, Aki; Lee, Ray X; Iwasato, Takuji; Itohara, Shigeyoshi; Arima, Hiroshi; Bettler, Bernhard; Miczek, Klaus A; Koide, Tsuyoshi

2015-04-22

Although the dorsal raphe nucleus (DRN) has long been linked to neural control of aggression, little is known about the regulatory influences of the DRN when an animal engages in either adaptive species-typical aggressive behavior or escalated aggression. Therefore it is important to explore which neurotransmitter inputs into the DRN determine the escalation of aggression in male mice. Previously, we observed that microinjection of the GABAB receptor agonist baclofen into the DRN escalates aggressive behavior in male mice. Here, we used a serotonin (5-HT) neuron-specific GABAB receptor knock-out mouse to demonstrate that baclofen acts on nonserotonergic neurons to escalate aggression. Intra-DRN baclofen administration increased glutamate release, but did not alter GABA release, within the DRN. Microinjection of l-glutamate into the DRN escalated dose-dependently attack bites toward an intruder. In vivo microdialysis showed that glutamate release increased in the DRN during an aggressive encounter, and the level of glutamate was further increased when the animal was engaged in escalated aggressive behavior after social instigation. Finally, 5-HT release was increased within the DRN and also in the medial prefrontal cortex when animals were provoked by social instigation, and during escalated aggression after social instigation, but this increase in 5-HT release was not observed when animals were engaged in species-typical aggression. In summary, glutamate input into the DRN is enhanced during escalated aggression, which causes a phasic increase of 5-HT release from the DRN 5-HT neurons. Copyright © 2015 the authors 0270-6474/15/356452-12$15.00/0.

Results From the First‐in‐Human Study With Ozanimod, a Novel, Selective Sphingosine‐1‐Phosphate Receptor Modulator

PubMed Central

Hartung, Jeffrey P.; Peach, Robert J.; Boehm, Marcus F.; Rosen, Hugh; Smith, Heather; Brooks, Jennifer L.; Timony, Gregg A.; Olson, Allan D.; Gujrathi, Sheila; Frohna, Paul A.

2017-01-01

Abstract The sphingosine‐1‐phosphate 1 receptor (S1P1R) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells and plays a role in the regulation of chronic inflammation and lymphocyte egress from peripheral lymphoid organs. Ozanimod is an oral selective modulator of S1P1R and S1P5R receptors in clinical development for the treatment of chronic immune‐mediated, inflammatory diseases. This first‐in‐human study characterized the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy volunteers using a range of single and multiple doses (7 and 28 days) and a dose‐escalation regimen. Ozanimod was generally well tolerated up to a maximum single dose of 3 mg and multiple doses of 2 mg/d, with no severe adverse events (AEs) and no dose‐limiting toxicities. The most common ozanimod‐related AEs included headache, somnolence, dizziness, nausea, and fatigue. Ozanimod exhibited linear PK, high steady‐state volume of distribution (73–101 L/kg), moderate oral clearance (204–227 L/h), and an elimination half‐life of approximately 17 to 21 hours. Ozanimod produced a robust dose‐dependent reduction in total peripheral lymphocytes, with a median decrease of 65% to 68% observed after 28 days of dosing at 1 and 1.5 mg/d, respectively. Ozanimod selectivity affected lymphocyte subtypes, causing marked decreases in cells expressing CCR7 and variable decreases in subsets lacking CCR7. A dose‐dependent negative chronotropic effect was observed following the first dose, with the dose‐escalation regimen attenuating the first‐dose negative chronotropic effect. Ozanimod safety, PK, and PD properties support the once‐daily regimens under clinical investigation. PMID:28398597

Willingness to trade-off: An intermediate factor in patient decision-making regarding escalating care.

PubMed

Seng, Elizabeth K; Grinberg, Amy S; Fraenkel, Liana

2018-01-01

This study aimed to evaluate treatment necessity, treatment concern, and willingness to engage in decisional trade-offs in the context of treatment escalation decision-making. Participants ( n  = 147) recruited online were randomized to read a vignette about escalating care in psoriasis in a 2 (high treatment concern vs moderate treatment concern) × 2 (high perceived treatment necessity vs moderate perceived treatment necessity) design. High treatment concern was associated with choosing to defer treatment escalation and being unwilling to engage in decisional trade-offs if disease risk changed. Results highlight the importance of treatment concern and willingness trade-off in treatment escalation decision-making.

Willingness to trade-off: An intermediate factor in patient decision-making regarding escalating care

PubMed Central

Seng, Elizabeth K; Grinberg, Amy S; Fraenkel, Liana

2018-01-01

This study aimed to evaluate treatment necessity, treatment concern, and willingness to engage in decisional trade-offs in the context of treatment escalation decision-making. Participants (n = 147) recruited online were randomized to read a vignette about escalating care in psoriasis in a 2 (high treatment concern vs moderate treatment concern) × 2 (high perceived treatment necessity vs moderate perceived treatment necessity) design. High treatment concern was associated with choosing to defer treatment escalation and being unwilling to engage in decisional trade-offs if disease risk changed. Results highlight the importance of treatment concern and willingness trade-off in treatment escalation decision-making. PMID:29662681

Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor-prognosis pediatric brain tumors1

PubMed Central

Ziegler, David S.; Cohn, Richard J.; McCowage, Geoffrey; Alvaro, Frank; Oswald, Cecilia; Mrongovius, Robert; White, Les

2006-01-01

The objective of this study was to assess the efficacy of the VETOPEC regimen, a regimen of vincristine and etoposide with escalating doses of cyclophosphamide (CPA), in pediatric patients with high-risk brain tumors. Three consecutive studies by the Australia and New Zealand Children’s Cancer Study Group—VETOPEC I, Baby Brain 91, and VETOPEC II—have used a specific chemotherapy regimen of vincristine (VCR), etoposide (VP-16) and escalating CPA in patients with relapsed, refractory, or high-risk solid tumors. Patients in the VETOPEC II cohort were treated with very high dose CPA with peripheral blood stem cell (PBSC) rescue. We analyzed the subset of patients with high-risk brain tumors treated with these intensive VETOPEC-based protocols to assess the response, toxicity, and survival. We also assessed whether the use of very high dose chemotherapy with stem cell rescue improved the response rate or affected toxicity. Seventy-one brain tumor patients were treated with VETOPEC-based protocols. Of the 54 patients evaluable for tumor response, 17 had a complete response (CR) and 20 a partial response (PR) to treatment, which yielded an overall response rate of 69%. The CR + PR was 83% (19/23) for medulloblastomas, 56% (5/9) for primitive neuroectodermal tumors, 55% (6/11) for grade 3 and 4 astrocytomas, and 80% (6/8) for ependymomas. At a median follow-up of 36 months, overall survival for the entire cohort of 71 patients was 32%, with event-free survival of 13%. There were no toxic deaths within the PBSC-supported VETOPEC II cohort, despite higher CPA doses, compared with 7% among the non-PBSC patients. This regimen produces high response rates in a variety of very poor prognosis pediatric brain tumors. The maximum tolerated dose of CPA was not reached. Higher escalation in doses of CPA did not deliver a further improvement in response. With PBSC rescue in the VETOPEC II study, hematologic toxicity was no longer a limiting factor. The response rates observed support further development of this chemotherapy regimen. PMID:16443948

A Phase I/II Study of Escalating Doses of Bortezomib in Conjunction with High-Dose Melphalan as a Conditioning Regimen for Salvage Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma.

PubMed

Biran, Noa; Rowley, Scott D; Vesole, David H; Zhang, Shijia; Donato, Michele L; Richter, Joshua; Skarbnik, Alan P; Pecora, Andrew; Siegel, David S

2016-12-01

Escalating doses of bortezomib with high-dose melphalan was evaluated as as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory multiple myeloma (MM). MM patients with less than a partial remission (PR) (or 50% reduction) compared to their pretransplantation paraprotein parameters after a prior ASCT with melphalan conditioning, or who were in relapse after a prior autologous transplantation, were eligible for study. Bortezomib was dose escalated in steps of 1, 1.3, and 1.6 mg/m 2 (3 × 3 design) on days -4 and -1 before transplantation with melphalan 200 mg/m 2 given on day -2. Thirty-two patients were enrolled: 12 in the phase I dose escalation phase and an additional 20 in phase II to gain additional experience with the regimen. Twenty-four (75%) patients were Durie Salmon stage III, and 12 (37.5%) had >2 prior lines of therapy. The overall response rate (≥PR) was 44% with 22% complete remission. Two-year overall survival and progression-free survival were 76% and 39%, respectively, with a median follow-up of 31.7 months. The most common grade 3 and 4 nonhematologic adverse events were neutropenic fever (25%), nausea (18.8%), and mucositis (9.4%). Serious adverse events included intensive care unit admission (9.4%), seizure (3.1%), prolonged diarrhea (3.1%), and Guillain-Barre syndrome (3.1%). Two patients (6%) died of sepsis. There was no emergent peripheral neuropathy nor increase in any pre-existing peripheral neuropathy. The addition of bortezomib to melphalan as conditioning for salvage ASCT was well tolerated. More importantly, it can provide durable remission for patients who have a suboptimal response to prior single-agent melphalan conditioning for ASCT, without requiring a reduction in the dose of melphalan. Larger randomized prospective studies to determine the effect of combination conditioning are being conducted. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Clinical benefits of antimicrobial de-escalation in adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia.

PubMed

Lee, Ching-Chi; Wang, Jiun-Ling; Lee, Chung-Hsun; Hung, Yuan-Pin; Hong, Ming-Yuan; Tang, Hung-Jen; Ko, Wen-Chien

2017-09-01

The clinical benefits of an antimicrobial de-escalation strategy were compared with those of a no-switch strategy in bacteremic patients. Adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia treated empirically using broad-spectrum beta-lactams, including third-generation cephalosporins (GCs), fourth-GC or carbapenems, were treated definitively with first- or second-GCs (de-escalation group), the same regimens as empirical antibiotics (no-switch group), or antibiotics with a broader-spectrum than empirical antibiotics (escalation group). The eligible 454 adults were categorized as the de-escalation (231 patients, 50.9%), no-switch (177, 39.0%), and escalation (46, 10.1%) groups. Patients with de-escalation therapy were more often female, had less critical illness and fatal comorbidity, and had a higher survival rate than patients in the other two groups. After propensity score matching in the de-escalation and no-switch groups, critical illness at onset (Pitt bacteremia score ≥ 4; 16.5% vs. 12.7%; P = 0.34) or day 3 (2.5% vs. 2.5%; P = 1.00), fatal comorbidity (16.5% vs. 21.5%; P = 0.25), time to defervescence (4.6 vs. 4.7 days; P = 0.89), hospital stays (11.5 vs. 10.3 days; P = 0.13) and 4-week crude mortality rate (4.4% vs. 4.4%; P = 1.00) were similar. However, lower antibiotic cost (mean: 212.1 vs. 395.6 US$, P <0.001) and fewer complications of bloodstream infections due to resistant pathogens (0% vs. 5.1%, P = 0.004) were observed in the de-escalation group. De-escalation to narrower-spectrum cephalosporins is safe and cost-effective for adults with community-onset EKP bacteremia stabilized by empirical broad-spectrum beta-lactams. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Maximum likelihood sequence estimation for optical complex direct modulation.

PubMed

Che, Di; Yuan, Feng; Shieh, William

2017-04-17

Semiconductor lasers are versatile optical transmitters in nature. Through the direct modulation (DM), the intensity modulation is realized by the linear mapping between the injection current and the light power, while various angle modulations are enabled by the frequency chirp. Limited by the direct detection, DM lasers used to be exploited only as 1-D (intensity or angle) transmitters by suppressing or simply ignoring the other modulation. Nevertheless, through the digital coherent detection, simultaneous intensity and angle modulations (namely, 2-D complex DM, CDM) can be realized by a single laser diode. The crucial technique of CDM is the joint demodulation of intensity and differential phase with the maximum likelihood sequence estimation (MLSE), supported by a closed-form discrete signal approximation of frequency chirp to characterize the MLSE transition probability. This paper proposes a statistical method for the transition probability to significantly enhance the accuracy of the chirp model. Using the statistical estimation, we demonstrate the first single-channel 100-Gb/s PAM-4 transmission over 1600-km fiber with only 10G-class DM lasers.

Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial.

PubMed

Engert, Andreas; Haverkamp, Heinz; Kobe, Carsten; Markova, Jana; Renner, Christoph; Ho, Antony; Zijlstra, Josée; Král, Zdenek; Fuchs, Michael; Hallek, Michael; Kanz, Lothar; Döhner, Hartmut; Dörken, Bernd; Engel, Nicole; Topp, Max; Klutmann, Susanne; Amthauer, Holger; Bockisch, Andreas; Kluge, Regine; Kratochwil, Clemens; Schober, Otmar; Greil, Richard; Andreesen, Reinhard; Kneba, Michael; Pfreundschuh, Michael; Stein, Harald; Eich, Hans Theodor; Müller, Rolf-Peter; Dietlein, Markus; Borchmann, Peter; Diehl, Volker

2012-05-12

The intensity of chemotherapy and need for additional radiotherapy in patients with advanced stage Hodgkin's lymphoma has been unclear. We did a prospective randomised clinical trial comparing two reduced-intensity chemotherapy variants with our previous standard regimen. Chemotherapy was followed by PET-guided radiotherapy. In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18-60 years were randomly assigned to receive either eight cycles of BEACOPP(escalated) (8×B(esc) group), six cycles of BEACOPP(escalated) (6×B(esc) group), or eight cycles of BEACOPP(14) (8×B(14) group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2·5 cm or larger and positive on PET scan received additional radiotherapy with 30 Gy; the negative predictive value for tumour recurrence of PET at 12 months was an independent endpoint. This trial is registered with Current Controlled Trials, number ISRCTN32443041. Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8×B(esc) group, 711 in the 6×B(esc) group, and 710 in the 8×B(14) group. Freedom from treatment failure was sequentially non-inferior for the 6×B(esc) and 8×B(14) groups as compared with 8×B(esc). 5-year freedom from treatment failure rates were 84·4% (97·5% CI 81·0-87·7) for the 8×B(esc) group, 89·3% (86·5-92·1) for 6×B(esc) group, and 85·4% (82·1-88·7) for the 8×B(14) group (97·5% CI for difference between 6×B(esc) and 8×B(esc) was 0·5-9·3). Overall survival in the three groups was 91·9%, 95·3%, and 94·5% respectively, and was significantly better with 6×B(esc) than with 8×B(esc) (97·5% CI 0·2-6·5). The 8×B(esc) group showed a higher mortality (7·5%) than the 6×B(esc) (4·6%) and 8×B(14) (5·2%) groups, mainly due to differences in treatment-related events (2·1%, 0·8%, and 0·8%, respectively) and secondary malignancies (1·8%, 0·7%, and 1·1%, respectively). The negative predictive value for PET at 12 months was 94·1% (95% CI 92·1-96·1); and 225 (11%) of 2126 patients received additional radiotherapy. Treatment with six cycles of BEACOPP(escalated) followed by PET-guided radiotherapy was more effective in terms of freedom from treatment failure and less toxic than eight cycles of the same chemotherapy regimen. Thus, six cycles of BEACOPP(escalated) should be the treatment of choice for advanced stage Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional radiotherapy in this setting. Deutsche Krebshilfe and the Swiss Federal Government. Copyright © 2012 Elsevier Ltd. All rights reserved.

The anesthetic effects on vasopressor modulation of cerebral blood flow in an immature swine model.

PubMed

Bruins, Benjamin; Kilbaugh, Todd J; Margulies, Susan S; Friess, Stuart H

2013-04-01

The effect of various sedatives and anesthetics on vasopressor modulation of cerebral blood flow (CBF) in children is unclear. In adults, isoflurane has been described to decrease CBF to a lesser extent than fentanyl and midazolam. Most large-animal models of neurocritical care use inhaled anesthetics for anesthesia. Investigations involving modulations of CBF would have improved translatability within a model that more closely approximates the current practice in the pediatric intensive care unit. Fifteen 4-week-old piglets were given 1 of 2 anesthetic protocols: total IV anesthesia (TIVA) (midazolam 1 mg/kg/h and fentanyl 100 μg/kg/h, n = 8) or ISO (isoflurane 1.5%-2% and fentanyl 100 μg/kg/h, n = 7). Mean arterial blood pressure, intracranial pressure (ICP), CBF, and brain tissue oxygen tension were measured continuously as piglets were exposed to escalating doses of arginine vasopressin, norepinephrine (NE), and phenylephrine (PE). Baseline CBF was similar in the 2 groups (ISO 38 ± 10 vs TIVA 35 ± 26 mL/100 g/min) despite lower baseline cerebral perfusion pressure in the ISO group (45 ± 11 vs 71 ± 11 mm Hg; P < 0.0005). Piglets in the ISO group displayed increases in ICP with PE and NE (11 ± 4 vs 16 ± 4 mm Hg and 11 ± 8 vs 18 ± 5 mm Hg; P < 0.05), but in the TIVA group, only exposure to PE resulted in increases in ICP when comparing maximal dose values with baseline data (11 ± 4 vs 15 ± 5 mm Hg; P < 0.05). Normalized CBF displayed statistically significant increases regarding anesthetic group and vasopressor dose when piglets were exposed to NE and PE (P < 0.05), suggesting an impairment of autoregulation within ISO, but not TIVA. The vasopressor effect on CBF was limited when using a narcotic-benzodiazepine-based anesthetic protocol compared with volatile anesthetics, consistent with a preservation of autoregulation. Selection of anesthetic drugs is critical to investigate mechanisms of cerebrovascular hemodynamics, and in translating critical care investigations between the laboratory and bedside.

Pseudomonas aeruginosa ventilator-associated pneumonia management

PubMed Central

Ramírez-Estrada, Sergio; Borgatta, Bárbara; Rello, Jordi

2016-01-01

Ventilator-associated pneumonia is the most common infection in intensive care unit patients associated with high morbidity rates and elevated economic costs; Pseudomonas aeruginosa is one of the most frequent bacteria linked with this entity, with a high attributable mortality despite adequate treatment that is increased in the presence of multiresistant strains, a situation that is becoming more common in intensive care units. In this manuscript, we review the current management of ventilator-associated pneumonia due to P. aeruginosa, the most recent antipseudomonal agents, and new adjunctive therapies that are shifting the way we treat these infections. We support early initiation of broad-spectrum antipseudomonal antibiotics in present, followed by culture-guided monotherapy de-escalation when susceptibilities are available. Future management should be directed at blocking virulence; the role of alternative strategies such as new antibiotics, nebulized treatments, and vaccines is promising. PMID:26855594

Pseudomonas aeruginosa ventilator-associated pneumonia management.

PubMed

Ramírez-Estrada, Sergio; Borgatta, Bárbara; Rello, Jordi

2016-01-01

Ventilator-associated pneumonia is the most common infection in intensive care unit patients associated with high morbidity rates and elevated economic costs; Pseudomonas aeruginosa is one of the most frequent bacteria linked with this entity, with a high attributable mortality despite adequate treatment that is increased in the presence of multiresistant strains, a situation that is becoming more common in intensive care units. In this manuscript, we review the current management of ventilator-associated pneumonia due to P. aeruginosa, the most recent antipseudomonal agents, and new adjunctive therapies that are shifting the way we treat these infections. We support early initiation of broad-spectrum antipseudomonal antibiotics in present, followed by culture-guided monotherapy de-escalation when susceptibilities are available. Future management should be directed at blocking virulence; the role of alternative strategies such as new antibiotics, nebulized treatments, and vaccines is promising.

Romantic relationship development in the age of Facebook: an exploratory study of emerging adults' perceptions, motives, and behaviors.

PubMed

Fox, Jesse; Warber, Katie M

2013-01-01

Social networking sites are becoming a prevalent form of communication in the escalation of romantic relationships. An online survey (n=403) addressed emerging adults' experiences with Facebook and romantic relationships, particularly a unique affordance of Facebook: the ability to declare oneself as "In a Relationship" and actively link one's profile to a romantic partner's, commonly known as going Facebook official. Results identified common social perceptions of the meaning of this status (regarding commitment, intensity, and social response) and both interpersonal and social motives for posting it on Facebook. Additionally, sex differences were identified in perceptions of meaning, wherein women felt this status conveyed commitment and intensity moreso than men did. Implications of this discrepancy on heterosexual relationship satisfaction and the prevailing role of technology in romantic relationships are discussed.

Modulation of spinal reflexes by sexual films of increasing intensity.

PubMed

Both, Stephanie; Boxtel, Geert; Stekelenburg, Jeroen; Everaerd, Walter; Laan, Ellen

2005-11-01

Sexual arousal can be viewed as an emotional state generating sex-specific autonomic and general somatic motor system responses that prepare for sexual action. In the present study modulation of spinal tendious (T) reflexes by sexual films of varying intensity was investigated. T reflexes were expected to increase as a function of increased film intensity. Through use of a between-subjects design, participants were exposed to three erotic films of low, moderate, and high intensity or to three films of moderate intensity. Self-report and genital data confirmed the induction of increasing versus stable levels of sexual arousal. Exposure to the films of increasing intensity resulted in increasing T reflexes. The results indicate that T reflex modulation is sensitive to varying levels of sexual arousal and may be of use in research on behavioral mechanisms underlying appetitive motivation.

[A comparative study of the effectiveness and tolerability of a procedure involving slow dose-escalation of rivastigmine in patients with mild or moderate Alzheimer-type dementia: the SCALEX study].

PubMed

Agüera-Ortiz, L F; Ramos-García, M; Gobartt, A L

To determine and to compare the tolerability and effectiveness of a slow escalation of the dose of rivastigmine in patients with Alzheimer's disease with respect to using it with a faster escalation. We conducted a multi-centre, naturalistic, open-label, randomised trial with 429 hospital outpatients diagnosed with Alzheimer-type dementia (according to DSM-IV and NINCDS-ADRA criteria) and in whom treatment with rivastigmine was clinically indicated. Two study groups were established: slow escalation and fast escalation (in accordance with usual clinical practice); effectiveness and tolerability variables were analysed in the two groups, as was the proportion of patients who reached therapeutic doses (> 6 mg/day). The scores obtained on the CGI, MMSE, NPI and Barthel index scales were analysed, together with adverse events and reactions concerning spontaneous communication, and scores on the UKU scale. The slow escalation group displayed slightly higher percentages of sub-therapeutic anticipated interruptions than the fast escalation group (chi-square test; p < 0.05). On comparing the two treatment groups, no statistically significant differences were observed for the evolution of the scores on the different scales of effectiveness; no statistically significant differences were found between the two groups in the safety and tolerability analyses (chi-square test, exact test; p > 0.05) for most of the parameters that were studied (adverse reactions in spontaneous communication and the modified UKU scale). Slow escalation of the dose of rivastigmine did not display greater effectiveness or tolerability in comparison to an escalation applied in accordance with usual clinical practice.

Controlled generation of high-intensity optical rogue waves by induced modulation instability

PubMed Central

Zhao, Saili; Yang, Hua; Chen, Nengsong; Zhao, Chujun

2017-01-01

Optical rogue waves are featured as the generation of high amplitude events at low probability in optical systems. Moreover, the formation of optical rogue waves is unpredictable and transient in photonic crystal fibers. In this paper, we put forward a method to generate high-intensity optical rogue waves in a more controlled way based on induced modulation instability, which can suppress the noise effect and hence play a leading role in the process of pulse evolution. Our numerical simulations indicate that the generation of rogue wave can be controlled when seeding at the optimal modulation frequency and the intensity of rogue wave can be enhanced with appropriate modulation depth. Further, high-intensity rogue wave can also be ejected in the fiber with a shorter propagation length by regulating the modulation depth. These results all provide a better understanding of optical rogue wave, which can contribute to the generation of tunable long-wavelength spectral components and selective excitation of mid-infrared supercontinuum. PMID:28051149

Controlled generation of high-intensity optical rogue waves by induced modulation instability.

PubMed

Zhao, Saili; Yang, Hua; Chen, Nengsong; Zhao, Chujun

2017-01-04

Optical rogue waves are featured as the generation of high amplitude events at low probability in optical systems. Moreover, the formation of optical rogue waves is unpredictable and transient in photonic crystal fibers. In this paper, we put forward a method to generate high-intensity optical rogue waves in a more controlled way based on induced modulation instability, which can suppress the noise effect and hence play a leading role in the process of pulse evolution. Our numerical simulations indicate that the generation of rogue wave can be controlled when seeding at the optimal modulation frequency and the intensity of rogue wave can be enhanced with appropriate modulation depth. Further, high-intensity rogue wave can also be ejected in the fiber with a shorter propagation length by regulating the modulation depth. These results all provide a better understanding of optical rogue wave, which can contribute to the generation of tunable long-wavelength spectral components and selective excitation of mid-infrared supercontinuum.

[Ethical case discussions in the intensive care unit : from testing to routine].

PubMed

Meyer-Zehnder, B; Barandun Schäfer, U; Albisser Schleger, H; Reiter-Theil, S; Pargger, H

2014-06-01

The daily work of many healthcare professionals has become more complex and demanding in recent years. Apart from purely medical issues, ethical questions and problems arise quite often. Managing these problems requires ethical knowledge. Questions about the usefulness of a therapy and treatment occur especially at the end of life. So-called medical futility, a useless futile therapy, is often perceived by nurses and physicians in intensive care units who themselves often develop symptoms of depression or burnout. The clinical ethical model METAP (acronym from module, ethics, therapy decision, allocation and process) provides methods and criteria that allow the clinical team to treat and solve ethical issues according to a solution-oriented approach. The ethical decision-making of this model addresses these issues according to a series of sequential stages in the form of a so-called escalation model. When it is not possible to tackle and solve an ethical problem or dilemma in one stage, one moves to the next. The implementation of this approach in everyday practice requires the commitment of all team members in addition to certain basic conditions. In a surgical intensive care unit a fixed date in the schedule is reserved for ethical case discussions (level 3 of the escalation model). At this level a team member who has been specified according to a quarterly plan is responsible for the organization and performance of the discussion. All protocols of the 44 ethical case discussions in 41 patients between January 2011 and July 2012 were collected and summarized. A short questionnaire to all participants recorded their assessment of the benefits for the patient and the team as well as their perception of personal stress reduction. Also queried was the impact of this method on the collaboration between nurses and physicians and the ethical competence. Ethical case discussions among the care team took place regularly (44 case discussions between January 2011 and June 2012). The duration of these discussions ranged from 30 to 60 min. On average 6.2 persons took part, including 2.7 nurses and 3.2 physicians. Of the 41 patients (16 female, 25 male) for whom a discussion was carried out, 23 died during the continued hospital stay. The respondents (response rate 52 %) assessed the benefit for patients and team as high (slightly higher benefit for physicians than nurses) and 55 % of physicians and 71 % of nurses perceived a reduction in the burden of decision-making in difficult cases due to the case discussions. All physicians and 66 % of the nurses reported an improvement in the cooperation between the professional groups and 80 % of the nurses and more than half of the physicians noticed an increase in their own ethical competence. A methodically structured ethical decision-making process can and should be integrated into the clinical routine. This process requires a fixed place in everyday practice and the defined responsibility for the actual organization and performance. Support by medical and nursing management personnel is also essential for the implementation. The regular occurrence of ethical case discussions among the care team relieves the participants and improves collaboration between nurses and physicians.

Demonstration of a simplified optical mouse lighting module by integrating the non-Lambertian LED chip and the free-form surface.

PubMed

Pan, Jui-Wen; Tu, Sheng-Han

2012-05-20

A cost-effective, high-throughput, and high-yield method for the efficiency enhancement of an optical mouse lighting module is proposed. We integrated imprinting technology and free-form surface design to obtain a lighting module with high illumination efficiency and uniform intensity distribution. The imprinting technique can increase the light extraction efficiency and modulate the intensity distribution of light-emitting diodes. A modulated light source was utilized to add a compact free-form surface element to create a lighting module with 95% uniformity and 80% optical efficiency.

Extinction-ratio-independent electrical method for measuring chirp parameters of Mach-Zehnder modulators using frequency-shifted heterodyne.

PubMed

Zhang, Shangjian; Wang, Heng; Zou, Xinhai; Zhang, Yali; Lu, Rongguo; Liu, Yong

2015-06-15

An extinction-ratio-independent electrical method is proposed for measuring chirp parameters of Mach-Zehnder electric-optic intensity modulators based on frequency-shifted optical heterodyne. The method utilizes the electrical spectrum analysis of the heterodyne products between the intensity modulated optical signal and the frequency-shifted optical carrier, and achieves the intrinsic chirp parameters measurement at microwave region with high-frequency resolution and wide-frequency range for the Mach-Zehnder modulator with a finite extinction ratio. Moreover, the proposed method avoids calibrating the responsivity fluctuation of the photodiode in spite of the involved photodetection. Chirp parameters as a function of modulation frequency are experimentally measured and compared to those with the conventional optical spectrum analysis method. Our method enables an extinction-ratio-independent and calibration-free electrical measurement of Mach-Zehnder intensity modulators by using the high-resolution frequency-shifted heterodyne technique.

Modulation of chorus intensity by ULF waves deep in the inner magnetosphere

DOE PAGES

Xia, Zhiyang; Chen, Lunjin; Dai, Lei; ...

2016-09-05

Previous studies have shown that chorus wave intensity can be modulated by Pc4-Pc5 compressional ULF waves. In this paper, we present Van Allen Probes observation of ULF wave modulating chorus wave intensity, which occurred deep in the magnetosphere. The ULF wave shows fundamental poloidal mode signature and mirror mode compressional nature. The observed ULF wave can modulate not only the chorus wave intensity but also the distribution of both protons and electrons. Linear growth rate analysis shows consistence with observed chorus intensity variation at low frequency (f <~ 0.3f ce), but cannot account for the observed higher-frequency chorus waves, includingmore » the upper band chorus waves. This suggests the chorus waves at higher-frequency ranges require nonlinear mechanisms. Finally, in addition, we use combined observations of Radiation Belt Storm Probes (RBSP) A and B to verify that the ULF wave event is spatially local and does not last long.« less

Contest experience and body size affect different types of contest decisions.

PubMed

Chen, Yu-Ju; Hsu, Yuying

2016-11-01

This study examined the relative importance of contest experience and size differences to behavioral decisions over the course of contests. Using a mangrove rivulus fish, Kryptolebias marmoratus, we showed that although contest experience and size differences jointly determined contest outcomes, they affected contestants' interactions at different stages of contests. Contest experience affected behavioral decisions at earlier stages of contests, including the tendency and latency to launch attacks, the tendency to escalate contests into mutual attacks and the outcome of non-escalated contests. Once contests were escalated into mutual attacks, the degree of size difference affected the fish's persistence in escalation and chance of winning, but contest experience did not. These results support the hypothesis that contest experience modifies individuals' estimation of their fighting ability rather than their actual strength. Furthermore, (1) in contests between two naïve contestants, more than 60 % of fish that were 2-3 mm smaller than their opponent escalated the contest to physical fights, even though their larger opponents eventually won 92 % of escalated fights and (2) fish with a losing experience were very likely to retreat in the face of an opponent 2-3 mm smaller than them without escalating. The result that a 2-3 mm size advantage could not offset the influence of a losing experience on the tendency to escalate suggests that, as well as depending on body size, the fish's physical strength is influenced by other factors which require further investigation.

A Systematic Review of the Definitions, Determinants, and Clinical Outcomes of Antimicrobial De-escalation in the Intensive Care Unit.

PubMed

Tabah, Alexis; Cotta, Menino Osbert; Garnacho-Montero, Jose; Schouten, Jeroen; Roberts, Jason A; Lipman, Jeffrey; Tacey, Mark; Timsit, Jean-François; Leone, Marc; Zahar, Jean Ralph; De Waele, Jan J

2016-04-15

Antimicrobial de-escalation (ADE) is a strategy to reduce the spectrum of antimicrobials and aims to prevent the emergence of bacterial resistance. We present a systematic review describing the definitions, determinants and outcomes associated with ADE. We included 2 randomized controlled trials and 12 cohort studies. There was considerable variability in the definition of ADE. It was more frequently performed in patients with broad-spectrum and/or appropriate antimicrobial therapy (P= .05 to .002), when more agents were used (P= .002), and in the absence of multidrug-resistant pathogens (P< .05). Where investigated, lower or improving severity scores were consistently associated with ADE (P= .04 to <.001). The pooled effect of ADE on mortality is protective (relative risk, 0.68; 95% confidence interval, .52-.88). Because the determinants of ADE are markers of clinical improvement and/or of lower risk of treatment failure this effect on mortality cannot be retained as evidence. None of the studies were designed to investigate the effect of ADE on antimicrobial resistance. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Do all patients in the phase I oncology trials need to be hospitalized? Domestic but outstanding issues for globalization of drug development in Japan.

PubMed

Shimomura, Akihiko; Kondo, Shunsuke; Kobayashi, Noriko; Iwasa, Satoru; Kitano, Shigehisa; Tamura, Kenji; Fujiwara, Yutaka; Yamamoto, Noboru

2017-08-01

Most trials investigating new drugs around the world, including phase I trials, are conducted in outpatient clinics. However, in Japan, regulatory authority requirements and traditional domestic guidelines often require hospitalization of phase I study participants. Patients participating in single-agent phase I clinical trials at National Cancer Center Hospital between December 1996 and August 2014 were monitored. Toxicity requiring hospitalization is defined as toxicity that needs intensive treatment. Study designs were classified into three types: first-in-human (FIH) study, dose-escalation study (conventional dose-escalation study to determine maximum tolerated dose (MTD) in Japanese patients), and dose-finding study (to assess safety and pharmacokinetic profiles up to the MTD previously determined in the West). A total of 945 patients who participated in a variety of single-agent phase I clinical trials between December 1996 and August 2014 were included in this study. Patients participated in one of three study types: dose-escalation (n = 582, 62%), first-in-human (n = 129, 14%), or dose-finding (n = 234, 25%). A total of 76 study drugs were evaluated as part of this pool of phase I studies. Subdivided by mechanism of action, 20 (26%) were cytotoxic, 50 (66%) were molecularly targeted, and 6 (8%) were immune checkpoint inhibitor. Thirty-six patients (3.8%) had severe toxicities requiring hospitalization during the first cycle. The overall number of toxicities requiring hospitalization and/or grade 4 toxicities during any cycle was 5.0%. The frequency of severe toxicity that needs to be hospitalized was unexpectedly low. The data did not demonstrate the need for hospitalization in the phase I trials, suggesting that phase I trials in Japan could be conducted in outpatient settings.

Evaluation of early antimicrobial therapy adaptation guided by the BetaLACTA® test: a case-control study.

PubMed

Garnier, Marc; Rozencwajg, Sacha; Pham, Tài; Vimont, Sophie; Blayau, Clarisse; Hafiani, Mehdi; Fulgencio, Jean-Pierre; Bonnet, Francis; Mainardi, Jean-Luc; Arlet, Guillaume; Fartoukh, Muriel; Gallah, Salah; Quesnel, Christophe

2017-06-28

Rapid diagnostic tests detecting microbial resistance are needed for limiting the duration of inappropriateness of empirical antimicrobial therapy (EAT) in intensive care unit patients, besides reducing the use of broad-spectrum antibiotics. We hypothesized that the betaLACTA® test (BLT) could lead to early increase in the adequacy of antimicrobial therapy. This was a case-control study. Sixty-one patients with BLT-guided adaptation of EAT were prospectively included, and then matched with 61 "controls" having similar infection characteristics (community or hospital-acquired, and source of infection), in whom EAT was conventionally adapted to antibiogram results. Endpoints were to compare the proportion of appropriate (primary endpoint) and optimal (secondary endpoint) antimicrobial therapies with each of the two strategies, once microbiological sample culture results were available. Characteristics of patients, infections and EAT at inclusion were similar between groups. Nine early escalations of EAT occurred in the BLT-guided adaptation group, reaching 98% appropriateness vs. 77% in the conventional adaptation group (p < 0.01). The BLT reduced the time until escalation of an inappropriate EAT from 50.5 (48-73) to 27 (24-28) hours (p < 0.01). Seventeen early de-escalations occurred in the BLT-guided adaptation group, compared to one in the conventional adaptation group, reducing patients' exposure to broad-spectrum beta-lactam such as carbapenems. In multivariate analysis, use of the BLT was strongly associated with early appropriate (OR = 18 (3.4-333.8), p = 0.006) and optimal (OR = 35.5 (9.6-231.9), p < 0.001) antimicrobial therapies. Safety parameters were similar between groups. Our study suggests that a BLT-guided adaptation strategy may allow early beta-lactam adaptation from the first 24 hours following the beginning of sepsis management.

Out of the frying pan: New York City hospitals in an age of deregulation.

PubMed

Salit, Sharon; Fass, Steven; Nowak, Mark

2002-01-01

For several decades New York City hospitals had been distinguished by their tightly regulated environment, chronically weak finances, high occupancy rates, teaching intensity, dependency on public payers, low managed care penetration, and minimal merger activity. Then in the late 1990s a rapid convergence of forces--the Balanced Budget Act, managed care growth, state deregulation of commercial rates, escalating costs, and plunging hospital occupancy rates--threw the city's hospital industry into turmoil. In this paper we describe this period of turbulent change that has left most of the city's safety-net and small community hospitals near bankruptcy.

Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer.

PubMed

Eisbruch, Avraham; Ship, Jonathan A; Dawson, Laura A; Kim, Hyungjin M; Bradford, Carol R; Terrell, Jeffrey E; Chepeha, Douglas B; Teknos, Theodore N; Hogikyan, Norman D; Anzai, Yoshimi; Marsh, Lon H; Ten Haken, Randall K; Wolf, Gregory T

2003-07-01

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is suggested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control.

Switching circuit to improve the frequency modulation difference-intensity THz quantum cascade laser imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saat, N. K.; Dean, P.; Khanna, S. P.

2015-04-24

We demonstrate new switching circuit for difference-intensity THz quantum cascade laser (QCL) imaging by amplitude modulation and lock in detection. The switching circuit is designed to improve the frequency modulation so that it can stably lock the amplitude modulation of the QCL and the detector output. The combination of a voltage divider and a buffer in switching circuit to quickly switch the amplitude of the QCL biases of 15.8 V and 17.2 V is successfully to increase the frequency modulation up to ∼100 Hz.

Dynamic optical modulation of an electron beam on a photocathode RF gun: Toward intensity-modulated radiation therapy (IMRT)

NASA Astrophysics Data System (ADS)

Kondoh, Takafumi; Kashima, Hiroaki; Yang, Jinfeng; Yoshida, Yoichi; Tagawa, Seiichi

2008-10-01

In intensity-modulated radiation therapy (IMRT), the aim is to deliver reduced doses of radiation to normal tissue. As a step toward IMRT, we examined dynamic optical modulation of an electron beam produced by a photocathode RF gun. Images on photomasks were transferred onto a photocathode by relay imaging. The resulting beam was controlled by a remote mirror. The modulated electron beam maintained its shape on acceleration, had a fine spatial resolution, and could be moved dynamically by optical methods.

The influence of fundamental frequency on perceived duration in spectrally comparable sounds

PubMed Central

Aalto, Daniel; Simko, Juraj; Vainio, Martti

2017-01-01

The perceived duration of a sound is affected by its fundamental frequency and intensity: higher sounds are judged to be longer, as are sounds with greater intensity. Since increasing intensity lengthens the perceived duration of the auditory object, and increasing the fundamental frequency increases the sound’s perceived loudness (up to ca. 3 kHz), frequency modulation of duration could be potentially explained by a confounding effect where the primary cause of the modulation would be variations in intensity. Here, a series of experiments are described that were designed to disentangle the contributions of fundamental frequency, intensity, and duration to perceived loudness and duration. In two forced-choice tasks, participants judged duration and intensity differences between two sounds varying simultaneously in intensity, fundamental frequency, fundamental frequency gliding range, and duration. The results suggest that fundamental frequency and intensity each have an impact on duration judgments, while frequency gliding range did not influence the present results. We also demonstrate that the modulation of perceived duration by sound fundamental frequency cannot be fully explained by the confounding relationship between frequency and intensity. PMID:28879063

The influence of fundamental frequency on perceived duration in spectrally comparable sounds.

PubMed

Dawson, Caitlin; Aalto, Daniel; Simko, Juraj; Vainio, Martti

2017-01-01

The perceived duration of a sound is affected by its fundamental frequency and intensity: higher sounds are judged to be longer, as are sounds with greater intensity. Since increasing intensity lengthens the perceived duration of the auditory object, and increasing the fundamental frequency increases the sound's perceived loudness (up to ca. 3 kHz), frequency modulation of duration could be potentially explained by a confounding effect where the primary cause of the modulation would be variations in intensity. Here, a series of experiments are described that were designed to disentangle the contributions of fundamental frequency, intensity, and duration to perceived loudness and duration. In two forced-choice tasks, participants judged duration and intensity differences between two sounds varying simultaneously in intensity, fundamental frequency, fundamental frequency gliding range, and duration. The results suggest that fundamental frequency and intensity each have an impact on duration judgments, while frequency gliding range did not influence the present results. We also demonstrate that the modulation of perceived duration by sound fundamental frequency cannot be fully explained by the confounding relationship between frequency and intensity.

Optical Limiting Using the Two-Photon Absorption Electrical Modulation Effect in HgCdTe Photodiode

PubMed Central

Cui, Haoyang; Yang, Junjie; Zeng, Jundong; Tang, Zhong

2013-01-01

The electrical modulation properties of the output intensity of two-photon absorption (TPA) pumping were analyzed in this paper. The frequency dispersion dependence of TPA and the electric field dependence of TPA were calculated using Wherrett theory model and Garcia theory model, respectively. Both predicted a dramatic variation of TPA coefficient which was attributed into the increasing of the transition rate. The output intensity of the laser pulse propagation in the pn junction device was calculated by using function-transfer method. It shows that the output intensity increases nonlinearly with increasing intensity of incident light and eventually reaches saturation. The output saturation intensity depends on the electric field strength; the greater the electric field, the smaller the output intensity. Consequently, the clamped saturation intensity can be controlled by the electric field. The prior advantage of electrical modulation is that the TPA can be varied extremely continuously, thus adjusting the output intensity in a wide range. This large change provides a manipulate method to control steady output intensity of TPA by adjusting electric field. PMID:24198721

29 CFR 1917.116 - Elevators and escalators.

Code of Federal Regulations, 2011 CFR

2011-07-01

... or more floors of a structure. The term excludes such devices as conveyors, tiering or piling... vicinity of the escalator or be available at the terminal. (f) Elevator landing openings shall be provided... landing, to prevent employees from falling into the shaft. (g) The elevator's or escalator's maximum load...

41 CFR 102-85.55 - What are the terms and conditions included in an OA?

Code of Federal Regulations, 2011 CFR

2011-01-01

... Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 85-PRICING... used; (d) Operating costs and escalations; (e) One time charges; e.g., lump sum payments by the customer; (f) Real estate tax and escalations; (g) Parking and escalations; (h) Additional/reduced services...

41 CFR 102-85.55 - What are the terms and conditions included in an OA?

Code of Federal Regulations, 2012 CFR

2012-01-01

... Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 85-PRICING... used; (d) Operating costs and escalations; (e) One time charges; e.g., lump sum payments by the customer; (f) Real estate tax and escalations; (g) Parking and escalations; (h) Additional/reduced services...

41 CFR 102-85.55 - What are the terms and conditions included in an OA?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 85-PRICING... used; (d) Operating costs and escalations; (e) One time charges; e.g., lump sum payments by the customer; (f) Real estate tax and escalations; (g) Parking and escalations; (h) Additional/reduced services...

41 CFR 102-85.55 - What are the terms and conditions included in an OA?

Code of Federal Regulations, 2014 CFR

2014-01-01

... Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 85-PRICING... used; (d) Operating costs and escalations; (e) One time charges; e.g., lump sum payments by the customer; (f) Real estate tax and escalations; (g) Parking and escalations; (h) Additional/reduced services...

A Comparison of Escalating versus Fixed Reinforcement Schedules on Undergraduate Quiz Taking

ERIC Educational Resources Information Center

Mahoney, Amanda

2017-01-01

Drug abstinence studies indicate that escalating reinforcement schedules maintain abstinence for longer periods than fixed reinforcement schedules. The current study evaluated whether escalating reinforcement schedules would maintain more quiz taking than fixed reinforcement schedules. During baseline and for the control group, bonus points were…

41 CFR 102-85.55 - What are the terms and conditions included in an OA?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 85-PRICING... used; (d) Operating costs and escalations; (e) One time charges; e.g., lump sum payments by the customer; (f) Real estate tax and escalations; (g) Parking and escalations; (h) Additional/reduced services...

The efficacy of procalcitonin as a biomarker in the management of sepsis: slaying dragons or tilting at windmills?

PubMed

Sridharan, Prasanna; Chamberlain, Ronald S

2013-12-01

Sepsis is defined as systemic inflammatory response syndrome (SIRS) in the context of an underlying infectious process, and is associated with high rates of morbidity and mortality, particularly when initial therapy is delayed. Numerous biomarkers, including but not limited to cytokines (interleukins-2 and -6 [IL-2, IL-6] and tumor necrosis factor-α [TNF-α]), leukotrienes, acute-phase proteins (C-reactive protein [CRP]), and adhesion molecules, have been evaluated and rejected as unsuitable for the diagnosis of sepsis, predicting its severity, and guiding its treatment. Most recently, procalcitonin (PCT) has been suggested as a novel biomarker that may be useful in guiding therapeutic decision making in the management of sepsis. This article assesses critically the published literature on the clinical utility of PCT concentrations for guiding the treatment of sepsis in adult patients. A comprehensive search of all published studies of the use of serum concentrations of PCT to guide the treatment of sepsis in adult patients (1996 to 2011) was conducted with PubMed and Google Scholar. The search focused on the value of PCT concentrations to guide the diagnosis, prognosis, monitoring, and escalation and de-escalation of antbiotic therapy in these patients. Keywords searched included "procalcitonin," "sepsis," "sepsis biomarker," "sepsis diagnosis," "sepsis prognosis," "sepsis mortality," "antibiotic escalation," "antibiotic de-escalation," "antibiotic duration," and "antimicrobial stewardship." Forty-six trials evaluating the efficacy of PCT concentrations in diagnosing sepsis have been published, with 39 of these trials yielding positive results and 7 yielding negative results. Wanner et al. published the largest study (n=405) demonstrating that peak PCT concentrations occur early after injury in both patients with sepsis and those with multiple organ dysfunction syndrome (MODS). Among 17 trials assessing the prognostic value of PCT concentrations with regard to clinical outcome and morbidity, 12 trials yielded positive results and five showed negative or equivocal results. Reith et al. published the largest study of the prognostic use of PCT concentrations (n=246), demonstrating that median PCT values on post-operative days (POD) one, four, and 10 were predictive of mortality in patients with abdominal sepsis (p<0.01). Among 14 trials of the utility of PCT concentrations for establishing an infectious cause of sepsis, 13 yielded positive results and only one yielded negative results. The largest study of this use of PCT concentrations, conducted by Baykut et al. (n=400), evaluated these concentrations in post-operative patients with infection, and demonstrated that concentrations of PCT remained elevated until POD 4, with a second increase observed between POD 4 and POD 6. In uninfected patients, PCT concentrations began to decrease on POD 2. Only a single study has assessed the utility of PCT concentrations in guiding the escalation of antibiotic therapy, and its results were negative. Specifically, Jensen et al. (n=1,200) compared a PCT-guided antibiotic escalation strategy with the standard of care for sepsis and found no difference in outcomes. They also found that the PCT group had a longer average stay in the intensive care unit (ICU), greater rates of mechanical ventilation, and a decreased estimated glomerular filtration rate (eGFR). Among four trials focusing on PCT concentrations and antibiotic de-escalation, all showed positive results with the measurement of PCT concentrations. The largest such study, by Bouadma et al. (n=621), demonstrated a four-day decrease in antibiotic duration when PCT concentrations were used to guide therapy relative to the study arm given the standard of care, with no increase in mortality (p=0.003). The diagnostic value of serum PCT concentrations for discriminating among SIRS, sepsis, severe sepsis, and septic shock remains to be established. Although higher PCT concentrations suggest a systemic bacterial infection as opposed to a viral, fungal, or inflammatory etiology of sepsis, serum PCT concentrations do not correlate with the severity of sepsis or with mortality. At present, PCT concentrations are solely investigational with regard to determining the timing and appropriateness of escalation of antimicrobial therapy in sepsis. Nevertheless, serum PCT concentrations have established utility in monitoring the clinical response to medical and surgical therapy for sepsis, and in surveillance for the development of sepsis in burn and ICU patients, and may have a role in guiding the de-escalation of antibiotic therapy.

Intensity modulation of HF heater-induced plasma lines

NASA Technical Reports Server (NTRS)

Kuo, S. P.; Lee, M. C.

1990-01-01

The Arecibo HF heater is normally composed of two separate sets of antenna array, transmitting waves vertically at the same frequency and polarization. However, when these two sets of antenna array radiate at slightly different frequencies, the intensities of HF heater-induced plasma lines (HFPLs) can be drastically modulated. In recent Duncan et al.'s (1989) experiments the 100 percent intensity modulation of HFPLs was seen to persist even when the secondary set of antenna array radiated at a few percent of the power transmitted by the primary set of antenna array. An explanation is offered, and it is shown that there exists a minimum power, Pmin, and if the secondary set of antenna array radiates at a power lower than Pmin, the 100-percent intensity modulation of HFPLs will not be observed. The functional dependence of Pmin on the difference frequency of the two sets of antenna array is also predicted for future experiments to corroborate.

Device to color modulate a stationary light beam gives high intensity

NASA Technical Reports Server (NTRS)

Gantz, W. A.

1966-01-01

Signal controlled system color modulates a beam of light while also providing high intensity and a stationary beam, either collimated or focused. The color modulation acquired by the presented system can be compatible with any color film by employing color filters formed to provide a color wedge having a color distribution compatible with the films color sensitivity.

Ionospheric very low frequency transmitter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuo, Spencer P.

2015-02-15

The theme of this paper is to establish a reliable ionospheric very low frequency (VLF) transmitter, which is also broad band. Two approaches are studied that generate VLF waves in the ionosphere. The first, classic approach employs a ground-based HF heater to directly modulate the high latitude ionospheric, or auroral electrojet. In the classic approach, the intensity-modulated HF heater induces an alternating current in the electrojet, which serves as a virtual antenna to transmit VLF waves. The spatial and temporal variations of the electrojet impact the reliability of the classic approach. The second, beat-wave approach also employs a ground-based HFmore » heater; however, in this approach, the heater operates in a continuous wave mode at two HF frequencies separated by the desired VLF frequency. Theories for both approaches are formulated, calculations performed with numerical model simulations, and the calculations are compared to experimental results. Theory for the classic approach shows that an HF heater wave, intensity-modulated at VLF, modulates the electron temperature dependent electrical conductivity of the ionospheric electrojet, which, in turn, induces an ac electrojet current. Thus, the electrojet becomes a virtual VLF antenna. The numerical results show that the radiation intensity of the modulated electrojet decreases with an increase in VLF radiation frequency. Theory for the beat wave approach shows that the VLF radiation intensity depends upon the HF heater intensity rather than the electrojet strength, and yet this approach can also modulate the electrojet when present. HF heater experiments were conducted for both the intensity modulated and beat wave approaches. VLF radiations were generated and the experimental results confirm the numerical simulations. Theory and experimental results both show that in the absence of the electrojet, VLF radiation from the F-region is generated via the beat wave approach. Additionally, the beat wave approach generates VLF radiations over a larger frequency band than by the modulated electrojet.« less

Understanding the Emotional Aspects of Escalation of Commitment: The Role of Negative Affect

ERIC Educational Resources Information Center

Wong, Kin Fai Ellick; Yik, Michelle; Kwong, Jessica Y. Y.

2006-01-01

Despite the importance of understanding the emotional aspects of organizational decision making, prior research has paid scant attention to the role of emotion in escalation of commitment. This article attempts to fill this gap by examining the relationship between negative affect and escalation of commitment. Results showed that regardless of…

Water and Wastewater Annual Price Escalation Rates for Selected Cities across the United States

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

Pacific Northwest National Laboratory conducted this study for the Federal Energy Management Program to identify trends in annual water and wastewater price escalation rates across the United States. This study can be used to inform the selection of an appropriate escalation rates for inclusion in LCCA.

Effect of climate-related mass extinctions on escalation in molluscs

NASA Astrophysics Data System (ADS)

Hansen, Thor A.; Kelley, Patricia H.; Melland, Vicky D.; Graham, Scott E.

1999-12-01

We test the hypothesis that escalated species (e.g., those with antipredatory adaptations such as heavy armor) are more vulnerable to extinctions caused by changes in climate. If this hypothesis is valid, recovery faunas after climate-related extinctions should include significantly fewer species with escalated shell characteristics, and escalated species should undergo greater rates of extinction than nonescalated species. This hypothesis is tested for the Cretaceous-Paleocene, Eocene-Oligocene, middle Miocene, and Pliocene-Pleistocene mass extinctions. Gastropod and bivalve molluscs from the U.S. coastal plain were evaluated for 10 shell characters that confer resistance to predators. Of 40 tests, one supported the hypothesis; highly ornamented gastropods underwent greater levels of Pliocene-Pleistocene extinction than did nonescalated species. All remaining tests were nonsignificant. The hypothesis that escalated species are more vulnerable to climate-related mass extinctions is not supported.

Light intensity modulation in phototherapy

NASA Astrophysics Data System (ADS)

Lukyanovich, P. A.; Zon, B. A.; Kunin, A. A.; Pankova, S. N.

2015-04-01

A hypothesis that blocking ATP synthesis is one of the main causes of the stimulating effect is considered based on analysis of the primary photostimulation mechanisms. The light radiation intensity modulation is substantiated and the estimates of such modulation parameters are made. An explanation is offered to the stimulation efficiency decrease phenomenon at the increase of the radiation dose during the therapy. The results of clinical research of the medical treatment in preventive dentistry are presented depending on the spectrum and parameters of the light flux modulation.

Cosmic Ray Helium Intensities over the Solar Cycle from ACE

NASA Technical Reports Server (NTRS)

DeNolfo, G. A.; Yanasak, N. E.; Binns, W. R.; Cohen, C. M. S.; Cummings, A. C.; Davis, A. J.; George, J. S.; Hink. P. L.; Israel, M. H.; Lave, K.;

Predicting the trajectories and intensities of hurricanes by applying machine learning techniques

NASA Astrophysics Data System (ADS)

Sujithkumar, A.; King, A. W.; Kovilakam, M.; Graves, D.

2017-12-01

The world has witnessed an escalation of devastating hurricanes and tropical cyclones over the last three decades. Hurricanes and tropical cyclones of very high magnitude will likely be even more frequent in a warmer world. Thus, precise forecasting of the track and intensity of hurricane/tropical cyclones remains one of the meteorological community's top priorities. However, comprehensive prediction of hurricane/ tropical cyclone is a difficult problem due to the many complexities of underlying physical processes with many variables and complex relations. The availability of global meteorological and hurricane/tropical storm climatological data opens new opportunities for data-driven approaches to hurricane/tropical cyclone modeling. Here we report initial results from two data-driven machine learning techniques, specifically, random forest (RF) and Bayesian learning (BL) to predict the trajectory and intensity of hurricanes and tropical cyclones. We used International Best Track Archive for Climate Stewardship (IBTrACS) data along with weather data from NOAA in a 50 km buffer surrounding each of the reported hurricane and tropical cyclone tracts to train the model. Initial results reveal that both RF and BL are skillful in predicting storm intensity. We will also present results for the more complicated trajectory prediction.

Total marrow irradiation using Helical TomoTherapy

NASA Astrophysics Data System (ADS)

Garcia-Fernandez, Lourdes Maria

Clinical dose response data of human tumours are limited or restricted to a radiation dose range determined by the level of toxicity to the normal tissues. This is the case for the most common disseminated plasma cell neoplasm, multiple myeloma, where the maximum dose deliverable to the entire bony skeleton using a standard total body irradiation (TBI) technique is limited to about 12 Gy. This study is part of scientific background of a phase I/II dose escalation clinical trial for multiple myeloma using image-guided intensity modulated radiotherapy (IG-IMRT) to deliver high dose to the entire volume of bone marrow with Helical TomoTherapy (HT). This relatively new technology can deliver highly conformal dose distributions to complex target shapes while reducing the dose to critical normal tissues. In this study tools for comparing and predicting the effectiveness of different approaches to total marrow irradiation (TMI) using HT were provided. The expected dose response for plasma cell neoplasms was computed and a radiobiological evaluation of different treatment cohorts in a dose escalating study was performed. Normal tissue complication probability (NTCP) and tumour control probability (TCP) models were applied to an actual TMI treatment plan for a patient and the implications of using different longitudinal field widths were assessed. The optimum dose was ˜39 Gy for which a predicted tumour control of 95% (+/-3%) was obtained, with a predicted 3% (0, 8%) occurrence of radiation pneumonitis. Tissue sparing was seen by using smaller field widths only in the organs of the head. This suggests it would be beneficial to use the small fields in the head only since using small fields for the whole treatment would lead to long treatment times. In TMI it may be necessary to junction two longitudinally adjacent treatment volumes to form a contiguous planning target volume PTV. For instance, this is the case when a different SUP-INF spatial resolution is required or when the PTV length exceeds the bed travel distance. In this work, the dosimetric challenges associated with junctioning longitudinally adjacent PTVs with HT were analyzed and the feasibility of PTV junctioning was demonstrated. The benefits of spatially dividing or splitting the treatment into a few sub-treatments along the longitudinal direction were also investigated.

A Novel Absorbable Radiopaque Hydrogel Spacer to Separate the Head of the Pancreas and Duodenum in Radiation Therapy for Pancreatic Cancer.

PubMed

Rao, Avani D; Feng, Ziwei; Shin, Eun Ji; He, Jin; Waters, Kevin M; Coquia, Stephanie; DeJong, Robert; Rosati, Lauren M; Su, Lin; Li, Dengwang; Jackson, Juan; Clark, Stephen; Schultz, Jeffrey; Hutchings, Danielle; Kim, Seong-Hun; Hruban, Ralph H; DeWeese, Theodore L; Wong, John; Narang, Amol; Herman, Joseph M; Ding, Kai

2017-12-01

We assessed the feasibility and theoretical dosimetric advantages of an injectable hydrogel to increase the space between the head of the pancreas (HOP) and duodenum in a human cadaveric model. Using 3 human cadaveric specimens, an absorbable radiopaque hydrogel was injected between the HOP and duodenum by way of open laparotomy in 1 case and endoscopic ultrasound (EUS) guidance in 2 cases. The cadavers were subsequently imaged using computed tomography and dissected for histologic confirmation of hydrogel placement. The duodenal dose reduction and planning target volume (PTV) coverage were characterized using pre- and postspacer injection stereotactic body radiation therapy (SBRT) plans for the 2 cadavers with EUS-guided placement, the delivery method that appeared the most clinically desirable. Modeling studies were performed using 60 SBRT plans consisting of 10 previously treated patients with unresectable pancreatic cancer, each with 6 different HOP-duodenum separation distances. The duodenal volume receiving 15 Gy (V15), 20 Gy (V20), and 33 Gy (V33) was assessed for each iteration. In the 3 cadaveric studies, an average of 0.9 cm, 1.1 cm, and 0.9 cm HOP-duodenum separation was achieved. In the 2 EUS cases, the V20 decreased from 3.86 cm 3 to 0.36 cm 3 and 3.75 cm 3 to 1.08 cm 3 (treatment constraint <3 cm 3 ), and the V15 decreased from 7.07 cm 3 to 2.02 cm 3 and 9.12 cm 3 to 3.91 cm 3 (treatment constraint <9 cm 3 ). The PTV coverage improved or was comparable between the pre- and postinjection studies. Modeling studies demonstrated that a separation of 8 mm was sufficient to consistently reduce the V15, V20, and V33 to acceptable clinical constraints. Currently, dose escalation has been limited owing to radiosensitive structures adjacent to the pancreas. We demonstrated the feasibility of hydrogel separation of the HOP and duodenum. Future studies will evaluate the safety and efficacy of this technique with the potential for more effective dose escalation using SBRT or intensity-modulated radiation therapy to improve the outcomes in patients with unresectable pancreatic cancer. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluating cardiac risk: exposure response analysis in early clinical drug development.

PubMed

Grenier, Julie; Paglialunga, Sabina; Morimoto, Bruce H; Lester, Robert M

2018-01-01

The assessment of a drug's cardiac liability has undergone considerable metamorphosis by regulators since International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use E14 guideline was introduced in 2005. Drug developers now have a choice in how proarrhythmia risk can be evaluated; the options include a dedicated thorough QT (TQT) study or exposure response (ER) modeling of intensive electrocardiogram (ECG) captured in early clinical development. The alternative approach of ER modeling was incorporated into a guidance document in 2015 as a primary analysis tool which could be utilized in early phase dose escalation studies as an option to perform a dedicated TQT trial. This review will describe the current state of ER modeling of intensive ECG data collected during early clinical drug development; the requirements with regard to the use of a positive control; and address the challenges and opportunities of this alternative approach to assessing QT liability.

Case Study of High-Dose Ketamine for Treatment of Complex Regional Pain Syndrome in the Pediatric Intensive Care Unit.

PubMed

Pasek, Tracy Ann; Crowley, Kelli; Campese, Catherine; Lauer, Rachel; Yang, Charles

2017-06-01

Complex regional pain syndrome (CRPS) is a life-altering and debilitating chronic pain condition. The authors are presenting a case study of a female who received high-dose ketamine for the management of her CRPS. The innovative treatment lies not only within the pharmacologic management of her pain, but also in the fact that she was the first patient to be admitted to our pediatric intensive care unit solely for pain control. The primary component of the pharmacotherapy treatment strategy plan was escalating-dose ketamine infusion via patient-controlled-analgesia approved by the pharmacy and therapeutics committee guided therapy for this patient. The expertise of advanced practice nurses blended exquisitely to ensure patient and family-centered care and the coordination of care across the illness trajectory. The patient experienced positive outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Extension of wavelength-modulation spectroscopy to large modulation depth for diode laser absorption measurements in high-pressure gases

NASA Astrophysics Data System (ADS)

Li, Hejie; Rieker, Gregory B.; Liu, Xiang; Jeffries, Jay B.; Hanson, Ronald K.

2006-02-01

Tunable diode laser absorption measurements at high pressures by use of wavelength-modulation spectroscopy (WMS) require large modulation depths for optimum detection of molecular absorption spectra blended by collisional broadening or dense spacing of the rovibrational transitions. Diode lasers have a large and nonlinear intensity modulation when the wavelength is modulated over a large range by injection-current tuning. In addition to this intensity modulation, other laser performance parameters are measured, including the phase shift between the frequency modulation and the intensity modulation. Following published theory, these parameters are incorporated into an improved model of the WMS signal. The influence of these nonideal laser effects is investigated by means of wavelength-scanned WMS measurements as a function of bath gas pressure on rovibrational transitions of water vapor near 1388 nm. Lock-in detection of the magnitude of the 2f signal is performed to remove the dependence on detection phase. We find good agreement between measurements and the improved model developed for the 2f component of the WMS signal. The effects of the nonideal performance parameters of commercial diode lasers are especially important away from the line center of discrete spectra, and these contributions become more pronounced for 2f signals with the large modulation depths needed for WMS at elevated pressures.

Attribution Bias and Overconfidence in Escalation of Commitment: The Role of Desire to Rectify Past Outcomes

ERIC Educational Resources Information Center

Tine, Delilah Castillo

2013-01-01

Escalation of commitment is the voluntary continuation of investing resources into what appears to be a failing course of action whose outcome is uncertain. Investigation into the escalation of commitment phenomenon is important to organizations because such behavior could result in grave economic loss. This research investigates two cognitive…

14 CFR Appendix A to Part 1215 - Estimated Service Rates in 1997 Dollars for TDRSS Standard Services (Based on NASA Escalation...

Code of Federal Regulations, 2014 CFR

2014-01-01

... Services (Based on NASA Escalation Estimate) Time: Project conceptualization (at least two years before... TDRSS Standard Services (Based on NASA Escalation Estimate) A Appendix A to Part 1215 Aeronautics and... the service requirements by NASA Headquarters, communications for the reimbursable development of a...

14 CFR Appendix A to Part 1215 - Estimated Service Rates in 1997 Dollars for TDRSS Standard Services (Based on NASA Escalation...

Code of Federal Regulations, 2013 CFR

2013-01-01

... Services (Based on NASA Escalation Estimate) Time: Project conceptualization (at least two years before... TDRSS Standard Services (Based on NASA Escalation Estimate) A Appendix A to Part 1215 Aeronautics and... the service requirements by NASA Headquarters, communications for the reimbursable development of a...

Development and Analysis of Security Policies in Security Enhanced Android

DTIC Science & Technology

2012-12-01

Privilege - Escalation Attacks on Android ,” Proc. 19th Annual...Services, Bethesda, MD, 2011, pp. 239–252. 98 [43] L. Davi, et al. “ Privilege Escalation Attacks on Android ,” Proc. 13th Int. Conf. on Information...TaintDroid. XManDroid dynamically analyzes applications’ transitive permission usage in order to prevent application-level privilege escalation attacks

Filter Bank Multicarrier (FBMC) for long-reach intensity modulated optical access networks

NASA Astrophysics Data System (ADS)

Saljoghei, Arsalan; Gutiérrez, Fernando A.; Perry, Philip; Barry, Liam P.

2017-04-01

Filter Bank Multi Carrier (FBMC) is a modulation scheme which has recently attracted significant interest in both wireless and optical communications. The interest in optical communications arises due to FBMC's capability to operate without a Cyclic Prefix (CP) and its high resilience to synchronisation errors. However, the operation of FBMC in optical access networks has not been extensively studied either in downstream or upstream. In this work we use experimental work to investigate the operation of FBMC in intensity modulated Passive Optical Networks (PONs) employing direct detection in conjunction with both direct and external modulation schemes. The data rates and propagation lengths employed here vary from 8.4 to 14.8 Gb/s and 0-75 km. The results suggest that by using FBMC it is possible to accomplish CP-Less transmission up to 75 km of SSMF in passive links using cost effective intensity modulation and detection schemes.

Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage—a modelling study

NASA Astrophysics Data System (ADS)

Røthe Arnesen, Marius; Paulsen Hellebust, Taran; Malinen, Eirik

2017-03-01

Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

High and escalating levels of cocaine intake are dissociable from subsequent incentive motivation for the drug in rats.

PubMed

Allain, Florence; Bouayad-Gervais, Karim; Samaha, Anne-Noël

2018-01-01

Taking high and increasing amounts of cocaine is thought to be necessary for the development of addiction. Consequently, a widely used animal model of drug self-administration involves giving animals continuous drug access during long sessions (LgA), as this produces high and escalating levels of intake. However, human cocaine addicts likely use the drug with an intermittent rather than continuous pattern, producing spiking brain cocaine levels. Using an intermittent-access (IntA) cocaine self-administration procedure in rats, we studied the relationship between escalation of cocaine intake and later incentive motivation for the drug, as measured by responding under a progressive ratio schedule of cocaine reinforcement. First, under IntA, rats escalated their cocaine use both within and between sessions. However, escalation did not predict later incentive motivation for the drug. Second, incentive motivation for cocaine was similar in IntA-rats limited to low- and non-escalating levels of drug intake (IntA-Lim) and in IntA-rats that took high and escalating levels of drug. Finally, IntA-Lim rats took much less cocaine than rats given continuous drug access during each self-administration session (LgA-rats). However, IntA-Lim rats later responded more for cocaine under a progressive ratio schedule of reinforcement. Taking large and escalating quantities of cocaine does not appear necessary to increase incentive motivation for the drug. Taking cocaine in an intermittent pattern-even in small amounts-is more effective in producing this addiction-relevant change. Thus, beyond the amount of drug taken, the temporal kinetics of drug use predict change in drug use over time.

Evaluation of empiric antibiotic de-escalation in febrile neutropenia.

PubMed

Kroll, Amanda L; Corrigan, Patricia A; Patel, Shejal; Hawks, Kelly G

2016-10-01

Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery. The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery. There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39). Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications. © The Author(s) 2015.

Individualized Radiation Dose Escalation Based on the Decrease in Tumor FDG Uptake and Normal Tissue Constraints Improve Survival in Patients With Esophageal Carcinoma.

PubMed

Ma, Jinbo; Wang, Zhaoyang; Wang, Chengde; Chen, Ercheng; Dong, Yaozong; Song, Yipeng; Wang, Wei; You, Dong; Jiang, Wei; Zang, Rukun

2017-02-01

To determine whether individualized radiation dose escalation after planned chemoradiation based on the decrease in tumor and normal tissue constraints can improve survival in patients with esophageal carcinoma. From August 2005 to December 2010, 112 patients with squamous esophageal carcinoma were treated with radical concurrent chemoradiation. Patients received positron emission tomography-computer tomography scan twice, before radiation and after radiation dose of 50.4 Gy. All patients were noncomplete metabolic response groups according to the Response Evaluation Criteria in solid tumors. Only 52 patients with noncomplete metabolic response received individualized dose escalation based on tumor and normal tissue constraints. Survival and treatment failure were observed and analyzed using SPSS (13.0). The rate of complete metabolic response for patients with noncomplete metabolic response after dose escalation reached 17.3% (9 of 52). The 2-year overall survival rates for patients with noncomplete metabolic response in the conventional and dose-escalation groups were 20.5% and 42.8%, respectively( P = .001). The 2-year local control rates for patients were 35.7% and 76.2%, respectively ( P = .002). When patients were classified into partial metabolic response and no metabolic response, 2-year overall survival rates for patients with partial metabolic response were significantly different in conventional and dose-escalation groups (33.8% vs 78.4%; P = .000). The 2-year overall survival rates for patients with no metabolic response in two groups (8.6% vs 15.1%) did not significantly differ ( P = .917). Individualized radiation dose escalation has the potential to improve survival in patients with esophageal carcinoma according to increased rate of complete metabolic response. However, further trials are needed to confirm this and to identify patients who may benefit from dose escalation.

The practices of expert psychiatric nurses: accompanying the patient to a calmer personal space.

PubMed

Johnson, M E; Hauser, P M

2001-01-01

The focus of the care of potentially aggressive psychiatric patients has been on the use of seclusion and restraints. Recent concerns, however, about the potential for patient injury have made it imperative that nurses use alternative methods to calm patients who are escalating. Little is known about how expert nurses de-escalate the escalating patient. The purpose of this interpretive phenomenological study was to uncover and describe the knowledge embedded in the stories of psychiatric nurses who are skilled in the practices of de-escalating an escalating patient. Twenty registered nurses were interviewed using an unstructured format. The analysis of the data revealed that these nurses were skilled at noticing the patient, reading the situation and the patient, knowing where the patient was on the continuum, understanding the meaning of the behavior, knowing what the patient needed, connecting with the patient, and matching the intervention with the patient's needs.

Treat-early and treat-mild: role of fast vs. slow escalation of headaches.

PubMed

Ng-Mak, D S; Ma, L; Hu, X H; Chen, Y-T

2009-04-01

This prospective, multi-center, observational study aimed to examine patients' early treatment decision process. Specifically, we assessed if the association between mild headache pain at treatment initiation and early treatment differed by the speed of headache escalation. Patients (n = 168) were instructed to collect information on their headache experience during the study period via an electronic diary over 30 consecutive days after enrollment. At the time of treatment, patients who treated early were 2.3 times as likely to experience mild headache pain as those who treated late. Controlling for the effect of escalation of headache, patients who treated early were three times as likely to report mild headache pain at dosing as those who treated late. The interaction between fast escalation of headache and mild pain was not statistically significant. Early treatment is associated with mild pain, regardless of the speed of headache escalation.

Wavelength reused bidirectional transmission of adaptively modulated optical OFDM signals in WDM-PONs incorporating SOA and RSOA intensity modulators.

PubMed

Wei, J L; Hugues-Salas, E; Giddings, R P; Jin, X Q; Zheng, X; Mansoor, S; Tang, J M

2010-05-10

Detailed numerical investigations are undertaken of wavelength reused bidirectional transmission of adaptively modulated optical OFDM (AMOOFDM) signals over a single SMF in a colorless WDM-PON incorporating a semiconductor optical amplifier (SOA) intensity modulator and a reflective SOA (RSOA) intensity modulator in the optical line termination and optical network unit, respectively. A comprehensive theoretical model describing the performance of such network scenarios is, for the first time, developed, taking into account dynamic optical characteristics of SOA and RSOA intensity modulators as well as the effects of Rayleigh backscattering (RB) and residual downstream signal-induced crosstalk. The developed model is rigorously verified experimentally in RSOA-based real-time end-to-end OOFDM systems at 7.5 Gb/s. It is shown that the RB noise and crosstalk effects are dominant factors limiting the maximum achievable downstream and upstream transmission performance. Under optimum SOA and RSOA operating conditions as well as practical downstream and upstream optical launch powers, 10 Gb/s downstream and 6 Gb/s upstream over 40 km SMF transmissions of conventional double sideband AMOOFDM signals are feasible without utilizing in-line optical amplification and chromatic dispersion compensation. In particular, the aforementioned transmission performance can be improved to 23 Gb/s downstream and 8 Gb/s upstream over 40 km SMFs when single sideband subcarrier modulation is adopted in the downstream systems. (c) 2010 Optical Society of America.

Electro-Optic Modulator and Method

DTIC Science & Technology

An optical intensity modulator which uses a Sagnac interferometer having an electro - optic phase modulator therein. An electric modulation signal is...modulating the optical signals by the electrical signal, the electro - optic effect in the modulator phase shifts the optical signals with respect to one another

Analysis of calibration-free wavelength-scanned wavelength modulation spectroscopy for practical gas sensing using tunable diode lasers

NASA Astrophysics Data System (ADS)

Sun, K.; Chao, X.; Sur, R.; Goldenstein, C. S.; Jeffries, J. B.; Hanson, R. K.

2013-12-01

A novel strategy has been developed for analysis of wavelength-scanned, wavelength modulation spectroscopy (WMS) with tunable diode lasers (TDLs). The method simulates WMS signals to compare with measurements to determine gas properties (e.g., temperature, pressure and concentration of the absorbing species). Injection-current-tuned TDLs have simultaneous wavelength and intensity variation, which severely complicates the Fourier expansion of the simulated WMS signal into harmonics of the modulation frequency (fm). The new method differs from previous WMS analysis strategies in two significant ways: (1) the measured laser intensity is used to simulate the transmitted laser intensity and (2) digital lock-in and low-pass filter software is used to expand both simulated and measured transmitted laser intensities into harmonics of the modulation frequency, WMS-nfm (n = 1, 2, 3,…), avoiding the need for an analytic model of intensity modulation or Fourier expansion of the simulated WMS harmonics. This analysis scheme is valid at any optical depth, modulation index, and at all values of scanned-laser wavelength. The method is demonstrated and validated with WMS of H2O dilute in air (1 atm, 296 K, near 1392 nm). WMS-nfm harmonics for n = 1 to 6 are extracted and the simulation and measurements are found in good agreement for the entire WMS lineshape. The use of 1f-normalization strategies to realize calibration-free wavelength-scanned WMS is also discussed.

Non-destructive phase and intensity distributed measurements of the nonlinear stage of modulation instability in optical fibers

NASA Astrophysics Data System (ADS)

Mussot, Arnaud; Naveau, Corentin; Szriftgiser, Pascal; Copie, François; Kudlinski, Alexandre; Conforti, Matteo; Trillo, Stefano

2018-02-01

We report a novel experimental setup to perform distributed characterization in intensity and phase of the nonlinear stage of modulation instability by means of a non-invasive experimental setup : a heterodyne time domain reflectometer.

Modulated grayscale UV pattern for uniform photopolymerization based on a digital micromirror device system

NASA Astrophysics Data System (ADS)

Yoon, Jinsik; Kim, Kibeom; Park, Wook

2017-07-01

We present an essential method for generating microparticles uniformly in a single ultraviolet (UV) light exposure area for optofluidic maskless lithography. In the optofluidic maskless lithography process, the productivity of monodisperse microparticles depends on the size of the UV exposure area. An effective fabrication area is determined by the size of the UV intensity profile map, satisfying the required uniformity of UV intensity. To increase the productivity of monodisperse microparticles in optofluidic maskless lithography, we expanded the effective UV exposure area by modulating the intensity of the desired UV light pattern based on the premeasured UV intensity profile map. We verified the improvement of the uniformity of the microparticles generated by the proposed modulation technique, providing histogram analyses of the conjugated fluorescent intensities and the sizes of the microparticles. Additionally, we demonstrated the generation of DNA uniformly encapsulated in microparticles.

Spatial Light Modulators with Arbitrary Quantum Wells Profiles

DTIC Science & Technology

1993-09-27

phase change in the 1.152Pm wave propagating through the waveguide and appears as an optically bistable intensity signal normal to the control beam ...electrical bistability of a SEED was integrated with a phase modulator to produce optical bistability in an all- optical switch. A control wavelength of...received attention for its use in electrically-addressable spatial light intensity modulator arrays due to its potentially high contrast ratio, large

Improving family satisfaction and participation in decision making in an intensive care unit.

PubMed

Huffines, Meredith; Johnson, Karen L; Smitz Naranjo, Linda L; Lissauer, Matthew E; Fishel, Marmie Ann-Michelle; D'Angelo Howes, Susan M; Pannullo, Diane; Ralls, Mindy; Smith, Ruth

2013-10-01

Background Survey data revealed that families of patients in a surgical intensive care unit were not satisfied with their participation in decision making or with how well the multidisciplinary team worked together. Objectives To develop and implement an evidence-based communication algorithm and evaluate its effect in improving satisfaction among patients' families. Methods A multidisciplinary team developed an algorithm that included bundles of communication interventions at 24, 72, and 96 hours after admission to the unit. The algorithm included clinical triggers, which if present escalated the algorithm. A pre-post design using process improvement methods was used to compare families' satisfaction scores before and after implementation of the algorithm. Results Satisfaction scores for participation in decision making (45% vs 68%; z = -2.62, P = .009) and how well the health care team worked together (64% vs 83%; z = -2.10, P = .04) improved significantly after implementation. Conclusions Use of an evidence-based structured communication algorithm may be a way to improve satisfaction of families of intensive care patients with their participation in decision making and their perception of how well the unit's team works together.

A conspiracy of optimism: Sustained yield, multiple use, and intensive management on the national forests, 1945-1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirt, P.W.

1991-01-01

This study focuses on two core national forest management policies; sustained yield and multiple use. Public and elected officials attempt to apply principles of sustainable development to publicly-owned forest lands to ensure that a wide variety of both market and nonmarket forest values are preserved for the benefit of present and future generations. Interest groups, the Forest Service, and policy makers have conceived of sustained yield and multiple use in different and evolving ways over the years. This study explores how these principles have been variously defined and either implemented or thwarted. After World War Two, with escalating demands onmore » national forest resources, the US Forest Service turned to intensive management as a technological method of enhancing natural forest productivity and mitigating the environmental effects of increased use. But the agency's optimistic vision of efficient, sustained production of forest commodities through technical mastery over nature has met overwhelming fiscal, environmental, technical, and political obstacles. Changing public values since the 1960s and popularization of ecology have initiated a growing skepticism toward the premises of intensive management.« less

77 FR 42353 - Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-18

... SMALL BUSINESS ADMINISTRATION [License No. 06/06-0335] Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Escalate Capital Partners SBIC I, L.P., 300 West 6th Street, Suite 2250...

75 FR 71785 - Escalate Capital Partners SBIC I, L.P., License No. 06/06-0335; Notice Seeking Exemption Under...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

... SMALL BUSINESS ADMINISTRATION Escalate Capital Partners SBIC I, L.P., License No. 06/06-0335; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Escalate Capital Partners, SBIC I, L.P., 300 W. 6th Street, Suite 2250...

76 FR 619 - Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... SMALL BUSINESS ADMINISTRATION [License No. 06/06-0335] Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Escalate Capital Partners, SBIC I, L.P., 300 W. 6th Street, Suite 2250...

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Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... SMALL BUSINESS ADMINISTRATION [License No. 06/06-0335] Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Escalate Capital Partners, SBIC I, L.P., 300 W. 6th Street, Suite 2250...

75 FR 45178 - Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

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42 CFR 405.1106 - Where a request for review or escalation may be filed.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Where a request for review or escalation may be filed. 405.1106 Section 405.1106 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... § 405.1016, the request for escalation must be filed with both the ALJ and the MAC. The appellant must...

42 CFR 405.1106 - Where a request for review or escalation may be filed.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Where a request for review or escalation may be filed. 405.1106 Section 405.1106 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... § 405.1016, the request for escalation must be filed with both the ALJ and the MAC. The appellant must...

Determinants of escalating costs in low risk workers' compensation claims.

PubMed

Bernacki, Edward J; Yuspeh, Larry; Tao, Xuguang

2007-07-01

To identify and quantify attributes that lead to unanticipated cost escalation in workers' compensation claims. We constructed four claim categories: low initial reserve/low cost, migrated catastrophic (low initial reserve/high cost), high initial reserve/low cost, and catastrophic (high initial reserve/high cost). To assess the attributes associated with the increased cost of migrated catastrophic claims, we analyzed 36,329 Louisiana workers' compensation claims in the four categories over a 5-year period. In the 729 claims initially thought to be low-cost claims (migrated catastrophic), the most significant predictors for cost escalation were attorney involvement and claim duration, followed by low back disorder, married/single/divorced status, male gender, small company size, high premium, reporting delays, and older age. These injuries accounted for 2% of all claims but 32.3% of the costs. Accelerated escalation of costs occurred late in the claim cycle (2 years). Certain attributes, particularly attorney involvement and claim duration, are associated with unanticipated cost escalation in a small number of claims that drastically affect overall losses. The results of this study suggest that these cases may be identified and addressed before rapid escalation occurs.

Olfactory signaling of aggressive intent in male-male contests of cave crickets (Troglophilus neglectus; Orthoptera: Rhaphidophoridae)

PubMed Central

Žunič Kosi, Alenka

2017-01-01

In animal contests, communicating aggressive motivation is most often mediated by visual or acoustic signals, while chemical signals are not expected to serve such a function since they are less able to be modulated by the sender during the changing behavioral context. We describe a rare example of ephemeral olfactory signals in terrestrial animals, signals that are emitted via protrusive scent glands in male cave crickets Troglophilus neglectus (Orthoptera, Rhaphidophoridae) to reflect the state of the signaler’s aggression. We correlate the intensity of behaviorally expressed aggression of the individuals in dyadic contests with the frequency and extent of their gland tissue protrusion, the latter serving as an indication of the amount of released odor. We detected large amounts of odor release during brief gland protrusions, and the absence of its release during gland retraction. Males protruded the glands during and after encountering a rival, with the degree of protrusion increasing with the intensity of the signalers’ aggression. During the encounters, the degree of gland protrusion increased most strongly with the occurrence of the elevated body posture, directly preceding the attack. This degree was significantly higher in encounter winners than in losers displaying such posture, suggesting the highly important role of the released odor for contest resolution. After the encounters, glands were protruded almost exclusively by winners, apparently announcing victory. We tested for the function of the olfactory signals also directly, by preventing gland tissue protrusion in symmetric and asymmetric treatments of the contestants. Treating only the dominant individuals decreased the percentage of encounters they won by over 60%, while treating both contestants elicited a significant increase in the frequency and duration of fights. During contests, the olfactory signals of T. neglectus apparently function as a highly effective threat, which prevents maximal contest escalation and decreases the conflict-related costs. PMID:29112984

Olfactory signaling of aggressive intent in male-male contests of cave crickets (Troglophilus neglectus; Orthoptera: Rhaphidophoridae).

PubMed

Stritih, Nataša; Žunič Kosi, Alenka

2017-01-01

In animal contests, communicating aggressive motivation is most often mediated by visual or acoustic signals, while chemical signals are not expected to serve such a function since they are less able to be modulated by the sender during the changing behavioral context. We describe a rare example of ephemeral olfactory signals in terrestrial animals, signals that are emitted via protrusive scent glands in male cave crickets Troglophilus neglectus (Orthoptera, Rhaphidophoridae) to reflect the state of the signaler's aggression. We correlate the intensity of behaviorally expressed aggression of the individuals in dyadic contests with the frequency and extent of their gland tissue protrusion, the latter serving as an indication of the amount of released odor. We detected large amounts of odor release during brief gland protrusions, and the absence of its release during gland retraction. Males protruded the glands during and after encountering a rival, with the degree of protrusion increasing with the intensity of the signalers' aggression. During the encounters, the degree of gland protrusion increased most strongly with the occurrence of the elevated body posture, directly preceding the attack. This degree was significantly higher in encounter winners than in losers displaying such posture, suggesting the highly important role of the released odor for contest resolution. After the encounters, glands were protruded almost exclusively by winners, apparently announcing victory. We tested for the function of the olfactory signals also directly, by preventing gland tissue protrusion in symmetric and asymmetric treatments of the contestants. Treating only the dominant individuals decreased the percentage of encounters they won by over 60%, while treating both contestants elicited a significant increase in the frequency and duration of fights. During contests, the olfactory signals of T. neglectus apparently function as a highly effective threat, which prevents maximal contest escalation and decreases the conflict-related costs.

Adaptive Dose Painting by Numbers for Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duprez, Frederic, E-mail: frederic.duprez@ugent.be; De Neve, Wilfried; De Gersem, Werner

Purpose: To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. Methods and Materials: Each patient's treatment used three separate treatment plans: fractions 1-10 used a DPBN ([{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography [{sup 18}F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment {sup 18}F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a {sup 18}F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gymore » to the high-dose clinical target volume (CTV{sub highdose}) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. Results: All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second {sup 18}F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV{sub highdose} (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV{sub highdose} and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. Conclusion: To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.« less

Gut–Brain Axis in Regulation of Blood Pressure

PubMed Central

Yang, Tao; Zubcevic, Jasenka

2017-01-01

Hypertension (HTN) is an escalating health issue worldwide. It is estimated that 1.56 billion people will suffer from high blood pressure (BP) by 2025. Recent studies reported an association between gut dysbiosis and HTN, thus proposing interesting avenues for novel treatments of this condition. The sympathetic nervous system (SNS) and the immune system (IS) play a recognized role in the onset and progression of HTN, while reciprocal communication between gut microbiota and the brain can regulate BP by modulating the interplay between the IS and SNS. This review presents the current state of the science implicating brain-gut connection in HTN, highlighting potential pathways of their interaction in control of BP. PMID:29118721

Optimization of combined electron and photon beams for breast cancer

NASA Astrophysics Data System (ADS)

Xiong, W.; Li, J.; Chen, L.; Price, R. A.; Freedman, G.; Ding, M.; Qin, L.; Yang, J.; Ma, C.-M.

2004-05-01

Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field.

System for obtaining smooth laser beams where intensity variations are reduced by spectral dispersion of the laser light (SSD)

DOEpatents

Skupsky, S.; Kessler, T.J.; Short, R.W.; Craxton, S.; Letzring, S.A.; Soures, J.

1991-09-10

In an SSD (smoothing by spectral dispersion) system which reduces the time-averaged spatial variations in intensity of the laser light to provide uniform illumination of a laser fusion target, an electro-optic phase modulator through which a laser beam passes produces a broadband output beam by imposing a frequency modulated bandwidth on the laser beam. A grating provides spatial and angular spectral dispersion of the beam. Due to the phase modulation, the frequencies (''colors'') cycle across the beam. The dispersed beam may be amplified and frequency converted (e.g., tripled) in a plurality of beam lines. A distributed phase plate (DPP) in each line is irradiated by the spectrally dispersed beam and the beam is focused on the target where a smooth (uniform intensity) pattern is produced. The color cycling enhances smoothing and the use of a frequency modulated laser pulse prevents the formation of high intensity spikes which could damage the laser medium in the power amplifiers. 8 figures.

System for obtaining smooth laser beams where intensity variations are reduced by spectral dispersion of the laser light (SSD)

DOEpatents

Skupsky, Stanley; Kessler, Terrance J.; Short, Robert W.; Craxton, Stephen; Letzring, Samuel A.; Soures, John

1991-01-01

In an SSD (smoothing by spectral dispersion) system which reduces the time-averaged spatial variations in intensity of the laser light to provide uniform illumination of a laser fusion target, an electro-optic phase modulator through which a laser beam passes produces a broadband output beam by imposing a frequency modulated bandwidth on the laser beam. A grating provides spatial and angular spectral dispersion of the beam. Due to the phase modulation, the frequencies ("colors") cycle across the beam. The dispersed beam may be amplified and frequency converted (e.g., tripled) in a plurality of beam lines. A distributed phase plate (DPP) in each line is irradiated by the spectrally dispersed beam and the beam is focused on the target where a smooth (uniform intensity) pattern is produced. The color cycling enhances smoothing and the use of a frequency modulated laser pulse prevents the formation of high intensity spikes which could damage the laser medium in the power amplifiers.

Adaptive correction to the speckle correlation fringes by using a twisted-nematic liquid-crystal display.

PubMed

Hack, Erwin; Gundu, Phanindra Narayan; Rastogi, Pramod

2005-05-10

An innovative technique for reducing speckle noise and improving the intensity profile of the speckle correlation fringes is presented. The method is based on reducing the range of the modulation intensity values of the speckle interference pattern. After the fringe pattern is corrected adaptively at each pixel, a simple morphological filtering of the fringes is sufficient to obtain smoothed fringes. The concept is presented both analytically and by simulation by using computer-generated speckle patterns. The experimental verification is performed by using an amplitude-only spatial light modulator (SLM) in a conventional electronic speckle pattern interferometry setup. The optical arrangement for tuning a commercially available LCD array for amplitude-only behavior is described. The method of feedback to the LCD SLM to modulate the intensity of the reference beam in order to reduce the modulation intensity values is explained, and the resulting fringe pattern and increase in the signal-to-noise ratio are discussed.

Improving IMRT delivery efficiency using intensity limits during inverse planning.

PubMed

Coselmon, Martha M; Moran, Jean M; Radawski, Jeffrey D; Fraass, Benedick A

2005-05-01

Inverse planned intensity modulated radiotherapy (IMRT) fields can be highly modulated due to the large number of degrees of freedom involved in the inverse planning process. Additional modulation typically results in a more optimal plan, although the clinical rewards may be small or offset by additional delivery complexity and/or increased dose from transmission and leakage. Increasing modulation decreases delivery efficiency, and may lead to plans that are more sensitive to geometrical uncertainties. The purpose of this work is to assess the use of maximum intensity limits in inverse IMRT planning as a simple way to increase delivery efficiency without significantly affecting plan quality. Nine clinical cases (three each for brain, prostate, and head/neck) were used to evaluate advantages and disadvantages of limiting maximum intensity to increase delivery efficiency. IMRT plans were generated using in-house protocol-based constraints and objectives for the brain and head/neck, and RTOG 9406 dose volume objectives in the prostate. Each case was optimized at a series of maximum intensity ratios (the product of the maximum intensity and the number of beams divided by the prescribed dose to the target volume), and evaluated in terms of clinical metrics, dose-volume histograms, monitor units (MU) required per fraction (SMLC and DMLC delivery), and intensity map variation (a measure of the beam modulation). In each site tested, it was possible to reduce total monitor units by constraining the maximum allowed intensity without compromising the clinical acceptability of the plan. Monitor unit reductions up to 38% were observed for SMLC delivery, while reductions up to 29% were achieved for DMLC delivery. In general, complicated geometries saw a smaller reduction in monitor units for both delivery types, although DMLC delivery required significantly more monitor units in all cases. Constraining the maximum intensity in an inverse IMRT plan is a simple way to improve delivery efficiency without compromising plan objectives.

Destined to die but not to wage war: how existential threat can contribute to escalation or de-escalation of violent intergroup conflict.

PubMed

Jonas, Eva; Fritsche, Immo

2013-10-01

War means threat to people's lives. Research derived from terror management theory (TMT) illustrates that the awareness of death leads people to defend cultural ingroups and their worldviews to attain a sense of symbolic immortality and thereby buffer existential anxiety. This can result in hostile effects of mortality salience (MS), such as derogation of outgroup members, prejudice, stereotyping, aggression, and racism, which, in turn, can lead to the escalation of violent intergroup conflict and, thus, the escalation of war. Yet, escalation of destructive conflict following MS is not automatic. Instead, research on TMT suggests that MS does not necessarily result in conflict and intolerance but can also foster positive tendencies, such as intergroup fairness or approval of pacifism, depending on how existential threat is perceived, whether the need for symbolic self-transcendence is satisfied, which social norms are salient, and how social situations are interpreted. In the present article, we review current TMT research with the aim of reconciling the seemingly contradictory findings of hostile and peaceful reactions to reminders of death. We present a terror management model of escalation and de-escalation of violent intergroup conflicts, which takes into account the interaction between threat salience and features of the social situation. We also discuss possible intervention strategies to override detrimental consequences of existential threat and argue that war is not the inevitable consequence of threat. PsycINFO Database Record (c) 2013 APA, all rights reserved

When less is best: female brown-headed cowbirds prefer less intense male displays.

PubMed

O'Loghlen, Adrian L; Rothstein, Stephen I

2012-01-01

Sexual selection theory predicts that females should prefer males with the most intense courtship displays. However, wing-spread song displays that male brown-headed cowbirds (Molothrus ater) direct at females are generally less intense than versions of this display that are directed at other males. Because male-directed displays are used in aggressive signaling, we hypothesized that females should prefer lower intensity performances of this display. To test this hypothesis, we played audiovisual recordings showing the same males performing both high intensity male-directed and low intensity female-directed displays to females (N = 8) and recorded the females' copulation solicitation display (CSD) responses. All eight females responded strongly to both categories of playbacks but were more sexually stimulated by the low intensity female-directed displays. Because each pair of high and low intensity playback videos had the exact same audio track, the divergent responses of females must have been based on differences in the visual content of the displays shown in the videos. Preferences female cowbirds show in acoustic CSD studies are correlated with mate choice in field and captivity studies and this is also likely to be true for preferences elucidated by playback of audiovisual displays. Female preferences for low intensity female-directed displays may explain why male cowbirds rarely use high intensity displays when signaling to females. Repetitive high intensity displays may demonstrate a male's current condition and explain why these displays are used in male-male interactions which can escalate into physical fights in which males in poorer condition could be injured or killed. This is the first study in songbirds to use audiovisual playbacks to assess how female sexual behavior varies in response to variation in a male visual display.

Nutrition Therapy in Sepsis.

PubMed

Wischmeyer, Paul E

2018-01-01

Sepsis is characterized by early massive catabolism, lean body mass (LBM) loss, and escalating hypermetabolism persisting for months to years. Early enteral nutrition should attempt to correct micronutrient/vitamin deficiencies, deliver adequate protein and moderated nonprotein calories, as well-nourished patients can generate reasonable endogenous energy. After resuscitation, increasing protein/calories are needed to attenuate LBM loss and promote recovery. Malnutrition screening is essential, and parenteral nutrition can be safely added when enteral nutrition is failing based on preillness malnutrition. Following discharge from intensive care unit, significantly increased protein/calorie delivery is required for months to years to facilitate functional and LBM recovery. Copyright © 2017 Elsevier Inc. All rights reserved.

Linking perceptions of role stress and incivility to workplace aggression: the moderating role of personality.

PubMed

Taylor, Shannon G; Kluemper, Donald H

2012-07-01

Although research on workplace aggression has long recognized job stressors as antecedents, little is known about the process through which employee responses to stressful workplace demands escalate from relatively mild interactions into more intense behaviors. This study investigates the influence that employees' perceptions of role stress (ambiguity, conflict, overload) have on their aggressive behavior by affecting their perceptions of incivility, and whether these downstream effects depend on personality traits (neuroticism, agreeableness, conscientiousness). Results supported moderated mediation, such that the indirect effects of perceived role ambiguity and role conflict on enacted aggression through experienced incivility varied according to individual differences in personality.

Nonlinear optical modulation in a plasmonic Bi:YIG Mach-Zehnder interferometer

NASA Astrophysics Data System (ADS)

Firby, C. J.; Elezzabi, A. Y.

2017-02-01

In this work, we propose a magnetoplasmonic modulator for nonlinear radio-frequency (RF) modulation of an integrated optical signal. The modulator consists of a plasmonic Mach-Zehnder interferometer (MZI), constructed of the ferrimagnetic garnet, bismuth-substituted yttrium iron garnet (Bi:YIG). The transverse component of the Bi:YIG magnetization induces a nonreciprocal phase shift (NRPS) onto the guided optical mode, which can be actively modulated through external magnetic fields. In an MZI, the modulated phase shift in turn modulates the output optical intensity. Due to the highly nonlinear evolution of the Bi:YIG magnetization, we show that the spectrum of the output modulated intensity signal can contain harmonics of the driving RF field, frequency splitting around the driving frequency, down-conversion, or mixing of multiple RF signals. This device provides a unique mechanism of simultaneously generating a number of modulation frequencies within a single device.

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner

PubMed Central

Cannady, Reginald; Fisher, Kristen R.; Graham, Caitlin; Crayle, Jesse; Besheer, Joyce; Hodge, Clyde W.

2015-01-01

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here we show that low-dose alcohol (0.6 g/kg/30-min) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala, and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared to behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol- but not sucrose-reinforced responding, and was ineffective following intra-AcbC infusion. Since GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor m-AIP dose-dependently reduced alcohol self-administration. A sub-threshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use via increased positive reinforcement during the initial stages of addiction. PMID:26742808

A Phase I Dose-Escalation Study of Danusertib (PHA-739358) Administered as a 24-hour Infusion With and Without G-CSF in a 14-day Cycle in Patients with Advanced Solid Tumors

PubMed Central

Cohen, Roger B.; Jones, Suzanne F.; Aggarwal, Charu; von Mehren, Margaret; Cheng, Jonathan; Spigel, David R.; Greco, F. Anthony; Mariani, Mariangela; Rocchetti, Maurizio; Ceruti, Roberta; Comis, Silvia; Laffranchi, Bernard; Moll, Jurgen; Burris, Howard A.

2009-01-01

Purpose This study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of the intravenous pan-aurora kinase inhibitor PHA-739358, danusertib, in patients with advanced solid tumors. Experimental Design In Part 1, patients received escalating doses of danusertib (24-h infusion every 14 days) without filgrastim (G-CSF). Febrile neutropenia was the dose-limiting toxicity without G-CSF. Further dose escalation was performed in part 2 with G-CSF. Blood samples were collected for danusertib pharmacokinetics and pharmacodynamics. Skin biopsies were collected to assess histone H3 phosphorylation (pH3). Results Fifty-six patients were treated, 40 in part 1 and 16 in part 2. Febrile neutropenia was the dose limiting toxicity in Part 1 without G-CSF. Most other adverse events were grade 1–2, occurring at doses ≥360 mg/m2 with similar incidence in parts 1 and 2. The MTD without G-CSF is 500 mg/m2. The recommended phase 2 dose (RP2D) in Part 2 with G-CSF is 750 mg/m2. Danusertib demonstrated dose-proportional pharmacokinetics in parts 1 and 2 with a median half-life of 18–26 hours. pH3 modulation in skin biopsies was observed at ≥500 mg/m2. One patient with refractory small cell lung cancer (1000 mg/m2 with G-CSF) had an objective response lasting 23 weeks. One patient with refractory ovarian cancer had 27% tumor regression and 30% CA125 decline. Conclusions Danusertib was well tolerated with target inhibition in skin at ≥500 mg/m2. Preliminary evidence of anti-tumor activity, including a PR and several occurrences of prolonged stable disease (SD), was seen across a variety of advanced refractory cancers. Phase II studies are ongoing. PMID:19825950

The Intensity Modulation of the Fluorescent Line by a Finite Light Speed Effect in Accretion-powered X-Ray Pulsars

NASA Astrophysics Data System (ADS)

Yoshida, Yuki; Kitamoto, Shunji; Hoshino, Akio

2017-11-01

The X-ray line diagnostic method is a powerful tool for an investigation of plasma around accretion-powered X-ray pulsars. We point out an apparent intensity modulation of emission lines, with their rotation period of neutron stars, due to the finite speed of light (we call this effect the “finite light speed effect”) if the line emission mechanism is a kind of reprocessing, such as fluorescence or recombination after ionization by X-ray irradiation from pulsars. The modulation amplitude is determined by the size of the emission region, which is in competition with the smearing effect by the light crossing time in the emission region. This is efficient if the size of the emission region is roughly comparable to that of the rotation period multiplied by the speed of light. We apply this effect to a symbiotic X-ray pulsar, GX 1+4, where a spin modulation of the intense iron line of which has been reported. The finite light speed effect can explain the observed intensity modulation if its fluorescent region is the size of ˜ {10}12 cm.

Infection-Mediated Vasoactive Peptides Modulate Cochlear Uptake of Fluorescent Gentamicin

PubMed Central

Koo, Ja-Won; Wang, Qi; Steyger, Peter S.

2011-01-01

Inflammatory mediators released during bacterial infection include vasoactive peptides such as histamine and serotonin, and their serum levels are frequently elevated. These peptides also modulate the vascular permeability of endothelial cells lining the blood-brain and blood-labyrinth barriers (BLB). These peptides may also modulate the permeability of the BLB to ototoxic aminoglycoside antibiotics prescribed to resolve bacterial sepsis. To test this hypothesis, we compared the effect of histamine and serotonin on the cochlear distribution of fluorescently conjugated gentamicin (GTTR) in control animals at 0.5, 1 and 3 h after injection of GTTR. The intensity of GTTR fluorescence was attenuated at 1 h in the histamine group compared to control mice, and more intense 3 h after injection (p < 0.05). In the serotonin group, the intensity of GTTR fluorescence was attenuated at 0.5 and 1 h (p < 0.05) and was increased at 3 h compared to control animals, where GTTR intensities peaked at 1 h and then plateaued or was slightly decreased at 3 h. This biphasic pattern of modulation was statistically significant in the apical turn of the cochlea. No difference in the intensity of GTTR fluorescence was observed in kidney proximal tubules. Systemic increases in serum levels of vasoactive peptides can modulate cochlear uptake of gentamicin, likely via permeability changes in the BLB. Conditions that influence serum levels of vasoactive peptides may potentiate aminoglycoside ototoxicity. PMID:21196726

Radiation proctopathy in the treatment of prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garg, Amit K.; Mai Weiyan; McGary, John E.

2006-12-01

Purpose: To compile and review data on radiation proctopathy in the treatment of prostate cancer with respect to epidemiology, clinical manifestations, pathogenesis, risk factors, and treatment. Methods: Medical literature databases including PubMed and Medline were screened for pertinent reports, and critically analyzed for relevance in the scope of our purpose. Results: Rectal toxicity as a complication of radiotherapy has received attention over the past decade, especially with the advent of dose-escalation in prostate cancer treatment. A number of clinical criteria help to define acute and chronic radiation proctopathy, but lack of a unified grading scale makes comparing studies difficult. Amore » variety of risk factors, related to either radiation delivery or patient, are the subject of intense study. Also, a variety of treatment options, including medical therapy, endoscopic treatments, and surgery have shown varied results, but a lack of large randomized trials evaluating their efficacy prevents forming concrete recommendations. Conclusion: Radiation proctopathy should be an important consideration for the clinician in the treatment of prostate cancer especially with dose escalation. With further study of possible risk factors, the advent of a standardized grading scale, and more randomized trials to evaluate treatments, patients and physicians will be better armed to make appropriate management decisions.« less

Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: De-escalation and rapid tranquillisation.

PubMed

Patel, Maxine X; Sethi, Faisil N; Barnes, Thomas Re; Dix, Roland; Dratcu, Luiz; Fox, Bernard; Garriga, Marina; Haste, Julie C; Kahl, Kai G; Lingford-Hughes, Anne; McAllister-Williams, Hamish; O'Brien, Aileen; Parker, Caroline; Paterson, Brodie; Paton, Carol; Posporelis, Sotiris; Taylor, David M; Vieta, Eduard; Völlm, Birgit; Wilson-Jones, Charlotte; Woods, Laura

2018-06-01

The British Association for Psychopharmacology and the National Association of Psychiatric Intensive Care and Low Secure Units developed this joint evidence-based consensus guideline for the clinical management of acute disturbance. It includes recommendations for clinical practice and an algorithm to guide treatment by healthcare professionals with various options outlined according to their route of administration and category of evidence. Fundamental overarching principles are included and highlight the importance of treating the underlying disorder. There is a focus on three key interventions: de-escalation, pharmacological interventions pre-rapid tranquillisation and rapid tranquillisation (intramuscular and intravenous). Most of the evidence reviewed relates to emergency psychiatric care or acute psychiatric adult inpatient care, although we also sought evidence relevant to other common clinical settings including the general acute hospital and forensic psychiatry. We conclude that the variety of options available for the management of acute disturbance goes beyond the standard choices of lorazepam, haloperidol and promethazine and includes oral-inhaled loxapine, buccal midazolam, as well as a number of oral antipsychotics in addition to parenteral options of intramuscular aripiprazole, intramuscular droperidol and intramuscular olanzapine. Intravenous options, for settings where resuscitation equipment and trained staff are available to manage medical emergencies, are also included.

Clinical utility of methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction assay in critically ill patients with nosocomial pneumonia.

PubMed

Smith, Melanie N; Erdman, Michael J; Ferreira, Jason A; Aldridge, Petra; Jankowski, Christopher A

2017-04-01

This study investigated the diagnostic performance characteristics of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) assay in critically ill patients with nosocomial pneumonia. This retrospective, single-center study included adult patients admitted to an intensive care unit with suspected nosocomial pneumonia. Patients must have received an MRSA nasal PCR assay and respiratory culture within predetermined time intervals. The primary outcome included the diagnostic performance characteristics of the assay. Secondary outcomes included the change in negative predictive value (NPV) over time, rate of acute kidney injury, and cost avoidance associated with vancomycin and monitoring. In 400 patients meeting inclusion criteria, the prevalence of culture confirmed MRSA pneumonia was 9.3%. When compared to initial cultures, the PCR assay demonstrated 91.89% sensitivity and 84.3% specificity with a positive predictive value and NPV of 37.36% and 99.03%. The NPV decreased to 87.5% at 21.9 days. No difference was found in rates of acute kidney injury. A cost avoidance of $108 per patient was estimated in patients de-escalated based on negative results. In critically ill patients, an MRSA nasal PCR assay has a high NPV for nosocomial pneumonia and can be used to guide vancomycin de-escalation. Copyright © 2016 Elsevier Inc. All rights reserved.

Progress in Y-00 physical cipher for Giga bit/sec optical data communications (intensity modulation method)

NASA Astrophysics Data System (ADS)

Hirota, Osamu; Futami, Fumio

2014-10-01

To guarantee a security of Cloud Computing System is urgent problem. Although there are several threats in a security problem, the most serious problem is cyber attack against an optical fiber transmission among data centers. In such a network, an encryption scheme on Layer 1(physical layer) with an ultimately strong security, a small delay, and a very high speed should be employed, because a basic optical link is operated at 10 Gbit/sec/wavelength. We have developed a quantum noise randomied stream cipher so called Yuen- 2000 encryption scheme (Y-00) during a decade. This type of cipher is a completely new type random cipher in which ciphertext for a legitimate receiver and eavesdropper are different. This is a condition to break the Shannon limit in theory of cryptography. In addition, this scheme has a good balance on a security, a speed and a cost performance. To realize such an encryption, several modulation methods are candidates such as phase-modulation, intensity-modulation, quadrature amplitude modulation, and so on. Northwestern university group demonstrated a phase modulation system (α=η) in 2003. In 2005, we reported a demonstration of 1 Gbit/sec system based on intensity modulation scheme(ISK-Y00), and gave a design method for quadratic amplitude modulation (QAM-Y00) in 2005 and 2010. An intensity modulation scheme promises a real application to a secure fiber communication of current data centers. This paper presents a progress in quantum noise randomized stream cipher based on ISK-Y00, integrating our theoretical and experimental achievements in the past and recent 100 Gbit/sec(10Gbit/sec × 10 wavelengths) experiment.

Reply to: Mounting evidence indicates that escalating doses of allopurinol are unnecessary for cardiovascular protection.

PubMed

Coburn, Brian W; Michaud, Kaleb; Bergman, Debra A; Mikuls, Ted R

2018-05-08

We thank Dr. Bredemeier for his comments regarding our manuscript on allopurinol dose escalation and mortality. He raises important evidence to consider in support of an interesting hypothesis that dose escalation may be unnecessary for allopurinol's cardiovascular (CV) protection and may actually be related to adverse CV outcomes. While we agree that evidence exists suggesting that low doses of allopurinol may be sufficient for CV protection, we believe that the studies cited highlight a number of areas where knowledge gaps remain which preclude any definitive conclusions about the effect of dose escalation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Escalation: How Much is Enough?

NASA Technical Reports Server (NTRS)

Butts, Glenn

2007-01-01

Determining the escalation percentage to an estimate is often the subject of fierce debate. Cost increases are determined by dynamic relati onships between many factors, including acts of nature, interest rate s, oil prices, global commodity markets, wars, wage rates, and the ov erall health of the economy, as well as supply and demand for the required goods or services. How much escalation is enough? Are the recen t price increases temporary aberrations, or will they continue to pla gue us? This paper examines historical escalation rates, as well as i ndications of trends. Various analysis methods -- Monte Carlo simulations, neural networks, trend impact analysis, and the Delphi method -- are examined in an attempt to determine future trends.

Ring resonator-based on-chip modulation transformer for high-performance phase-modulated microwave photonic links.

PubMed

Zhuang, Leimeng; Taddei, Caterina; Hoekman, Marcel; Leinse, Arne; Heideman, René; van Dijk, Paulus; Roeloffzen, Chris

2013-11-04

In this paper, we propose and experimentally demonstrate a novel wideband on-chip photonic modulation transformer for phase-modulated microwave photonic links. The proposed device is able to transform phase-modulated optical signals into intensity-modulated versions (or vice versa) with nearly zero conversion of laser phase noise to intensity noise. It is constructed using waveguide-based ring resonators, which features simple architecture, stable operation, and easy reconfigurability. Beyond the stand-alone functionality, the proposed device can also be integrated with other functional building blocks of photonic integrated circuits (PICs) to create on-chip complex microwave photonic signal processors. As an application example, a PIC consisting of two such modulation transformers and a notch filter has been designed and realized in TriPleX(TM) waveguide technology. The realized device uses a 2 × 2 splitting circuit and 3 ring resonators with a free spectral range of 25 GHz, which are all equipped with continuous tuning elements. The device can perform phase-to-intensity modulation transform and carrier suppression simultaneously, which enables high-performance phase-modulated microwave photonics links (PM-MPLs). Associated with the bias-free and low-complexity advantages of the phase modulators, a single-fiber-span PM-MPL with a RF bandwidth of 12 GHz (3 dB-suppression band 6 to 18 GHz) has been demonstrated comprising the proposed PIC, where the achieved spurious-free dynamic range performance is comparable to that of Class-AB MPLs using low-biased Mach-Zehnder modulators.

An agent-based hydroeconomic model to evaluate water policies in Jordan

NASA Astrophysics Data System (ADS)

Yoon, J.; Gorelick, S.

2014-12-01

Modern water systems can be characterized by a complex network of institutional and private actors that represent competing sectors and interests. Identifying solutions to enhance water security in such systems calls for analysis that can adequately account for this level of complexity and interaction. Our work focuses on the development of a hierarchical, multi-agent, hydroeconomic model that attempts to realistically represent complex interactions between hydrologic and multi-faceted human systems. The model is applied to Jordan, one of the most water-poor countries in the world. In recent years, the water crisis in Jordan has escalated due to an ongoing drought and influx of refugees from regional conflicts. We adopt a modular approach in which biophysical modules simulate natural and engineering phenomena, and human modules represent behavior at multiple scales of decision making. The human modules employ agent-based modeling, in which agents act as autonomous decision makers at the transboundary, state, organizational, and user levels. A systematic nomenclature and conceptual framework is used to characterize model agents and modules. Concepts from the Unified Modeling Language (UML) are adopted to promote clear conceptualization of model classes and process sequencing, establishing a foundation for full deployment of the integrated model in a scalable object-oriented programming environment. Although the framework is applied to the Jordanian water context, it is generalizable to other regional human-natural freshwater supply systems.

Study of modulation property to incident laser by surface micro-defects on KH2PO4 crystal

NASA Astrophysics Data System (ADS)

Chen, Ming-Jun; Cheng, Jian; Li, Ming-Quan; Xiao, Yong

2012-06-01

KH2PO4 crystal is a crucial optical component of inertial confinement fusion. Modulation of an incident laser by surface micro-defects will induce the growth of surface damage, which largely restricts the enhancement of the laser induced damage threshold. The modulation of an incident laser by using different kinds of surface defects are simulated by employing the three-dimensional finite-difference time-domain method. The results indicate that after the modulation of surface defects, the light intensity distribution inside the crystal is badly distorted, with the light intensity enhanced symmetrically. The relations between modulation properties and defect geometries (e.g., width, morphology, and depth of defects) are quite different for different defects. The modulation action is most obvious when the width of surface defects reaches 1.064 μm. For defects with smooth morphology, such as spherical pits, the degree of modulation is the smallest and the light intensity distribution seems relatively uniform. The degree of modulation increases rapidly with the increase of the depth of surface defects and becomes stable when the depth reaches a critical value. The critical depth is 1.064 μm for cuboid pits and radial cracks, while for ellipsoidal pits the value depends on both the width and the length of the defects.

Detection and rate discrimination of amplitude modulation in electrical hearing.

PubMed

Chatterjee, Monita; Oberzut, Cherish

2011-09-01

Three experiments were designed to examine temporal envelope processing by cochlear implant (CI) listeners. In experiment 1, the hypothesis that listeners' modulation sensitivity would in part determine their ability to discriminate between temporal modulation rates was examined. Temporal modulation transfer functions (TMTFs) obtained in an amplitude modulation detection (AMD) task were compared to threshold functions obtained in an amplitude modulation rate discrimination (AMRD) task. Statistically significant nonlinear correlations were observed between the two measures. In experiment 2, results of loudness-balancing showed small increases in the loudness of modulated over unmodulated stimuli beyond a modulation depth of 16%. Results of experiment 3 indicated small but statistically significant effects of level-roving on the overall gain of the TMTF, but no impact of level-roving on the average shape of the TMTF across subjects. This suggested that level-roving simply increased the task difficulty for most listeners, but did not indicate increased use of intensity cues under more challenging conditions. Data obtained with one subject, however, suggested that the most sensitive listeners may derive some benefit from intensity cues in these tasks. Overall, results indicated that intensity cues did not play an important role in temporal envelope processing by the average CI listener. © 2011 Acoustical Society of America

Validation and testing of the Acceptability E-scale for Web-based patient-reported outcomes in cancer care

PubMed Central

Tariman, Joseph D.; Berry, Donna L.; Halpenny, Barbara; Wolpin, Seth; Schepp, Karen

2010-01-01

The performance of the Acceptability E-scale was tested in a sample of 627 adult and older adult patients from various oncology clinics who completed an electronic symptoms survey. The revised Acceptability E-scale has strong psychometric properties and can be useful in assessing the acceptability and usability of computerized health-related programs in oncology and other health population. PMID:20974066

Subthreshold depressive disorder in adolescents: predictors of escalation to full-syndrome depressive disorders.

PubMed

Klein, Daniel N; Shankman, Stewart A; Lewinsohn, Peter M; Seeley, John R

2009-07-01

Subthreshold depressive disorder is one of the best established risk factors for the onset of full-syndrome depressive disorders. However, many youths with subthreshold depressive disorder do not develop full-syndrome depression. We examined predictors of escalation to full-syndrome depressive disorders in a community sample of 225 adolescents with subthreshold depressive disorder. Criteria for subthreshold depressive disorder were an episode of depressed mood or loss of interest or pleasure lasting at least 1 week and at least two of the seven other DSM-IV-associated symptoms for major depression. Participants were assessed four times from mid-adolescence to age 30 years using semistructured diagnostic interviews. The estimated risk for escalation to full-syndrome depressive disorders was 67%. Five variables accounted for unique variance in predicting escalation: severity of depressive symptoms, medical conditions/symptoms, history of suicidal ideation, history of anxiety disorder, and familial loading for depression. Adolescents with three or more risk factors had an estimated 90% chance of escalating to full-syndrome depressive disorder, compared with 47% of adolescents with fewer than three risk factors. These data may be useful in identifying a subgroup of youths with subthreshold depressive disorder who are at especially high risk for escalating to full-syndrome depressive disorders.

Subthreshold Depressive Disorder in Adolescents: Predictors of Escalation to Full-Syndrome Depressive Disorders

PubMed Central

KLEIN, DANIEL N.; SHANKMAN, STEWART A.; LEWINSOHN, PETER M.; SEELEY, JOHN R.

2010-01-01

Objectives Subthreshold depressive disorder is one of the best established risk factors for the onset of full-syndrome depressive disorders. However, many youths with subthreshold depressive disorder do not develop full-syndrome depression. We examined predictors of escalation to full-syndrome depressive disorders in a community sample of 225 adolescents with subthreshold depressive disorder. Method Criteria for subthreshold depressive disorder were an episode of depressed mood or loss of interest or pleasure lasting at least 1 week and at least two of the seven other DSM-IV-associated symptoms for major depression. Participants were assessed four times from mid-adolescence to age 30 years using semistructured diagnostic interviews. Results The estimated risk for escalation to full-syndrome depressive disorders was 67%. Five variables accounted for unique variance in predicting escalation: severity of depressive symptoms, medical conditions/symptoms, history of suicidal ideation, history of anxiety disorder, and familial loading for depression. Adolescents with three or more risk factors had an estimated 90% chance of escalating to full-syndrome depressive disorder, compared with 47% of adolescents with fewer than three risk factors. Conclusions These data may be useful in identifying a subgroup of youths with subthreshold depressive disorder who are at especially high risk for escalating to full-syndrome depressive disorders. PMID:19465876

Conflict escalation in paediatric services: findings from a qualitative study

PubMed Central

Forbat, Liz; Teuten, Bea; Barclay, Sarah

2015-01-01

Objective To explore clinician and family experiences of conflict in paediatric services, in order to map the trajectory of conflict escalation. Design Qualitative interview study, employing extreme-case sampling. Interviews were analysed using an iterative thematic approach to identify common themes regarding the experience and escalation of conflict. Participants Thirty-eight health professionals and eight parents. All participants had direct experience of conflict, including physical assault and court proceedings, at the interface of acute and palliative care. Setting Two teaching hospitals, one district general hospital and two paediatric hospices in England, in 2011. Results Conflicts escalate in a predictable manner. Clearly identifiable behaviours by both clinicians and parents are defined as mild, moderate and severe. Mild describes features like the insensitive use of language and a history of unresolved conflict. Moderate involves a deterioration of trust, and a breakdown of communication and relationships. Severe marks disintegration of working relationships, characterised by behavioural changes including aggression, and a shift in focus from the child's best interests to the conflict itself. Though conflicts may remain at one level, those which escalated tended to move sequentially from one level to the next. Conclusions Understanding how conflicts escalate provides clinicians with a practical, evidence-based framework to identify the warning signs of conflict in paediatrics. PMID:25940425

Results From the First-in-Human Study With Ozanimod, a Novel, Selective Sphingosine-1-Phosphate Receptor Modulator.

PubMed

Tran, Jonathan Q; Hartung, Jeffrey P; Peach, Robert J; Boehm, Marcus F; Rosen, Hugh; Smith, Heather; Brooks, Jennifer L; Timony, Gregg A; Olson, Allan D; Gujrathi, Sheila; Frohna, Paul A

2017-08-01

The sphingosine-1-phosphate 1 receptor (S1P 1R ) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells and plays a role in the regulation of chronic inflammation and lymphocyte egress from peripheral lymphoid organs. Ozanimod is an oral selective modulator of S1P 1R and S1P 5R receptors in clinical development for the treatment of chronic immune-mediated, inflammatory diseases. This first-in-human study characterized the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy volunteers using a range of single and multiple doses (7 and 28 days) and a dose-escalation regimen. Ozanimod was generally well tolerated up to a maximum single dose of 3 mg and multiple doses of 2 mg/d, with no severe adverse events (AEs) and no dose-limiting toxicities. The most common ozanimod-related AEs included headache, somnolence, dizziness, nausea, and fatigue. Ozanimod exhibited linear PK, high steady-state volume of distribution (73-101 L/kg), moderate oral clearance (204-227 L/h), and an elimination half-life of approximately 17 to 21 hours. Ozanimod produced a robust dose-dependent reduction in total peripheral lymphocytes, with a median decrease of 65% to 68% observed after 28 days of dosing at 1 and 1.5 mg/d, respectively. Ozanimod selectivity affected lymphocyte subtypes, causing marked decreases in cells expressing CCR7 and variable decreases in subsets lacking CCR7. A dose-dependent negative chronotropic effect was observed following the first dose, with the dose-escalation regimen attenuating the first-dose negative chronotropic effect. Ozanimod safety, PK, and PD properties support the once-daily regimens under clinical investigation. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Short-term selection for high and low ethanol intake yields differential sensitivity to ethanol's motivational effects and anxiety-like responses in adolescent Wistar rats.

PubMed

Fernández, Macarena Soledad; Báez, Bárbara; Bordón, Ana; Espinosa, Laura; Martínez, Eliana; Pautassi, Ricardo Marcos

2017-10-03

Alcohol use disorders are modulated by genetic factors, but the identification of specific genes and their concomitant biological changes that are associated with a higher risk for these disorders has proven difficult. Alterations in the sensitivity to the motivational effects of ethanol may be one way by which genes modulate the initiation and escalation of ethanol intake. Rats and mice have been selectively bred for high and low ethanol consumption during adulthood. However, selective breeding programs for ethanol intake have not focused on adolescence. This phase of development is associated with the initiation and escalation of ethanol intake and characterized by an increase in the sensitivity to ethanol's appetitive effects and a decrease in the sensitivity to ethanol's aversive effects compared with adulthood. The present study performed short-term behavioral selection to select rat lines that diverge in the expression of ethanol drinking during adolescence. A progenitor nucleus of Wistar rats (F 0 ) and filial generation 1 (F 1 ), F 2 , and F 3 adolescent rats were derived from parents that were selected for high (STDRHI) and low (STDRLO) ethanol consumption during adolescence and were tested for ethanol intake and responsivity to ethanol's motivational effects. STDRHI rats exhibited significantly greater ethanol intake and preference than STDRLO rats. Compared with STDRLO rats, STDRHI F 2 and F 3 rats exhibited a blunted response to ethanol in the conditioned taste aversion test. F 2 and F 3 STDRHI rats but not STDRLO rats exhibited ethanol-induced motor stimulation. STDRHI rats exhibited avoidance of the white compartment of the light-dark box, a reduction of locomotion, and a reduction of saccharin consumption, suggesting an anxiety-prone phenotype. The results suggest that the genetic risk for enhanced ethanol intake during adolescence is associated with lower sensitivity to the aversive effects of ethanol, heightened reactivity to ethanol's stimulating effects, and enhanced innate anxiety. Copyright © 2017 Elsevier Inc. All rights reserved.

Concepts on the pathogenesis of adolescent idiopathic scoliosis. Bone growth and mass, vertebral column, spinal cord, brain, skull, extra-spinal left-right skeletal length asymmetries, disproportions and molecular pathogenesis.

PubMed

Burwell, R Geoffrey; Dangerfield, Peter H; Freeman, Brian J C

2008-01-01

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). Encouraging advances thought to be related to AIS pathogenesis have recently been made in several fields including anthropometry of bone growth, bone mass, spinal growth modulation, extra-spinal left-right skeletal length asymmetries and disproportions, magnetic resonance imaging of vertebral column, spinal cord, brain, skull, and molecular pathogenesis. These advances are leading to the evaluation of new treatments including attempts at minimally invasive surgery on the spine and peri-apical ribs. Several concepts of AIS are outlined indicating their clinical applications but not their research potential. The concepts, by derivation morphological, molecular and mathematical, are addressed in 15 sections: 1) initiating and progressive factors; 2) relative anterior spinal overgrowth; 3) dorsal shear forces that create axial rotational instability; 4) rotational preconstraint; 5) uncoupled, or asynchronous, spinal neuro-osseous growth; 6) brain, nervous system and skull; 7) a novel neuro-osseous escalator concept based on a putative abnormality of two normal polarized processes namely, a) increasing skeletal dimensions, and b) the CNS body schema - both contained within a neuro-osseous timing of maturation (NOTOM) concept; 8) transverse plane pelvic rotation, skeletal asymmetries and developmental theory; 9) thoraco-spinal concept; 10) origin in contracture at the hips; 11) osteopenia; 12) melatonin deficiency; 13) systemic melatonin-signaling pathway dysfunction; 14) platelet calmodulin dysfunction; and 15) biomechanical spinal growth modulation. From these concepts, a collective model for AIS pathogenesis is formulated. The central concept of this model includes the body schema of the neural systems, widely-studied in adults, that control normal posture and coordinated movements with frames of reference in the posterior parietal cortex. The escalator concept has implications for the normal development of upright posture, and the evolution in humans of neural control, the trunk and unique bipedal gait.

Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

PubMed

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered.

Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

PubMed Central

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Background Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. PMID:27073327

Escalation to Major Depressive Disorder among Adolescents with Subthreshold Depressive Symptoms: Evidence of Distinct Subgroups at Risk

PubMed Central

Hill, Ryan M.; Pettit, Jeremy W.; Lewinsohn, Peter M.; Seeley, John R.; Klein, Daniel N.

2014-01-01

Background The presence of subthreshold depressive symptoms (SubD) in adolescence is associated with high prospective risk of developing Major Depressive Disorder (MDD). Little is known about variables that predict escalation from SubD to MDD. This study used a longitudinal prospective design in a community sample of adolescents to identify combinations of risk factors that predicted escalation from SubD to MDD. Methods Classification tree analysis was used to identify combinations of risk factors that improved the sensitivity and specificity of prediction of MDD onset among 424 adolescents with a lifetime history of SubD. Results Of the 424, 144 developed MDD during the follow-up period. Evidence for multiple subgroups was found: Among adolescents with poor friend support, the highest risk of escalation was among participants with lifetime histories of an anxiety or substance use disorder. Among adolescents with high friend support, those reporting multiple major life events in the past year or with a history of an anxiety disorder were at highest risk of escalation. Limitations Study findings may not inform prevention efforts for individuals who first develop SubD during adulthood. This study did not examine the temporal ordering of predictors involved in escalation from SubD to MDD. Conclusions Adolescents with a history of SubD were at highest risk of escalation to MDD in the presence of poor friend support and an anxiety or substance use disorder, or in the presence of better friend support, multiple major life events, and an anxiety disorder. Findings may inform case identification approaches for adolescent depression prevention programs. PMID:24655777

Change in Visual Field Progression Following Treatment Escalation in Primary Open-angle Glaucoma.

PubMed

Aptel, Florent; Bron, Alain M; Lachkar, Yves; Schweitzer, Cédric

2017-10-01

To evaluate the effect of treatment escalation on the rate of visual field progression in patients with primary open-angle glaucoma (POAG). Multicenter database study. We reviewed the electronic records of 171 patients with POAG under medical hypotensive treatment who underwent 5 consecutive visits 6 months apart before and after medical treatment escalation or additive laser trabeculoplasty. We calculated the rate of visual field progression (mean deviation change per year) before and after treatment escalation. The mean duration of follow-up was 5.1±0.5 years and the mean number of visual field examinations was 10.2±0.2. In 139 eyes with medical treatment escalation, the rate of progression was significantly reduced [from -0.57 to -0.29 dB/y; P=0.022; intraocular pressure (IOP) reduction 11.1%]. In detail, the rate of progression was significantly reduced after escalation from mono to dual therapy, dual to triple therapy, and from mono to triple therapy (-0.35 to -0.24 dB/y, P=0.018; -1.01 to -0.48 dB/y, P=0.038; -1.04 to -0.35 dB/y, P=0.020, respectively). In 32 eyes with additive laser trabeculoplasty, the rate of progression was significantly reduced (-0.60 to -0.24 dB/y; P=0.014; IOP reduction 9.4%). Medical treatment escalation or additive laser trabeculoplasty significantly reduced the rate of visual field progression in POAG. Larger IOP reduction has a greater probability of reducing glaucoma progression.

Developmental trends in alcohol use initiation and escalation from early- to middle-adolescence: Prediction by urgency and trait affect

PubMed Central

Spillane, Nichea S.; Merrill, Jennifer E.; Jackson, Kristina M.

2016-01-01

Studies on adolescent drinking have not always been able to distinguish between initiation and escalation of drinking, because many studies include samples in which initiation has already occurred; hence initiation and escalation are often confounded. The present study draws from a dual-process theoretical framework to investigate: if changes in the likelihood of drinking initiation and escalation are predicted by a tendency towards rash action when experiencing positive and negative emotions (positive and negative urgency); and whether trait positive and negative affect moderate such effects. Alcohol naïve adolescents (n=944; age: M=12.16, SD=.96; 52% female) completed 6 semi-annual assessments of trait urgency and affect (wave-1) and alcohol use (waves 2–6). A two-part random-effects model was used to estimate changes in the likelihood of any alcohol use vs. escalation in the volume of use amongst initiators. Main effects suggest a significant association between positive affect and change in level of alcohol use amongst initiators, such that lower positive affect predicted increased alcohol involvement. This main effect was qualified by a significant interaction between positive urgency and positive affect predicting changes in the escalation of drinking, such that the effect of positive urgency was augmented for those high on trait positive affect, though only at extremely high levels of positive affect. Results suggest risk factors in the development of drinking depend on whether initiation or escalation is investigated. A more nuanced understanding of the early developmental phases of alcohol involvement can inform prevention and intervention efforts. PMID:27031086

Care planning for aggression management in a specialist secure mental health service: An audit of user involvement.

PubMed

Hallett, Nutmeg; Huber, Jörg W; Sixsmith, Judith; Dickens, Geoffrey L

2016-12-01

This paper describes an audit of prevention and management of violence and aggression care plans and incident reporting forms which aimed to: (i) report the compliance rate of completion of care plans; (ii) identify the extent to which patients contribute to and agree with their care plan; (iii) describe de-escalation methods documented in care plans; and (iv) ascertain the extent to which the de-escalation methods described in the care plan are recorded as having been attempted in the event of an incident. Care plans and incident report forms were examined for all patients in men's and women's mental health care pathways who were involved in aggressive incidents between May and October 2012. In total, 539 incidents were examined, involving 147 patients and 121 care plans. There was no care plan in place at the time of 151 incidents giving a compliance rate of 72%. It was documented that 40% of patients had contributed to their care plans. Thematic analysis of de-escalation methods documented in the care plans revealed five de-escalation themes: staff interventions, interactions, space/quiet, activities and patient strategies/skills. A sixth category, coercive strategies, was also documented. Evidence of adherence to de-escalation elements of the care plan was documented in 58% of incidents. The reasons for the low compliance rate and very low documentation of patient involvement need further investigation. The inclusion of coercive strategies within de-escalation documentation suggests that some staff fundamentally misunderstand de-escalation. © 2016 Australian College of Mental Health Nurses Inc.

Design of Hybrid Silicon and Lithium Niobate Active Region for Electro-optical Modulation

DTIC Science & Technology

2017-03-01

bandwidth our group has proposed a Mach-Zehnder traveling -wave type modulator with optimized cross section dimensions using a similar material stack as...increases the electric field intensity available to the Pockel’s effect. At the same time , the induced metal loss increases as the electrodes become...Gopalakrishnan et al., “Performance and modeling of broadband LiNbO3 traveling wave optical intensity modulators,” J. Light. Technol., vol. 12, no. 10, pp

Deriving the solar activity cycle modulation on cosmic ray intensity observed by Nagoya muon detector from October 1970 until December 2012

NASA Astrophysics Data System (ADS)

de Mendonça, Rafael R. S.; Braga, Carlos. R.; Echer, Ezequiel; Dal Lago, Alisson; Rockenbach, Marlos; Schuch, Nelson J.; Munakata, Kazuoki

2017-10-01

It is well known that the cosmic ray intensity observed at the Earth's surface presents an 11 and 22-yr variations associated with the solar activity cycle. However, the observation and analysis of this modulation through ground muon detectors datahave been difficult due to the temperature effect. Furthermore, instrumental changes or temporary problems may difficult the analysis of these variations. In this work, we analyze the cosmic ray intensity observed since October 1970 until December 2012 by the Nagoya muon detector. We show the results obtained after analyzing all discontinuities and gaps present in this data and removing changes not related to natural phenomena. We also show the results found using the mass weighted method for eliminate the influence of atmospheric temperature changes on muon intensity observed at ground. As a preliminary result of our analyses, we show the solar cycle modulation in the muon intensity observed for more than 40 years.

Potential for reduced toxicity and dose escalation in the treatment of inoperable non-small-cell lung cancer: a comparison of intensity-modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal irradiation.

PubMed

Grills, Inga S; Yan, Di; Martinez, Alvaro A; Vicini, Frank A; Wong, John W; Kestin, Larry L

2003-11-01

To systematically evaluate four different techniques of radiation therapy (RT) used to treat non-small-cell lung cancer and to determine their efficacy in meeting multiple normal-tissue constraints while maximizing tumor coverage and achieving dose escalation. Treatment planning was performed for 18 patients with Stage I to IIIB inoperable non-small-cell lung cancer using four different RT techniques to treat the primary lung tumor +/- the hilar/mediastinal lymph nodes: (1) Intensity-modulated radiation therapy (IMRT), (2) Optimized three-dimensional conformal RT (3D-CRT) using multiple beam angles, (3) Limited 3D-CRT using only 2 to 3 beams, and (4) Traditional RT using elective nodal irradiation (ENI) to treat the mediastinum. All patients underwent virtual simulation, including a CT scan and (18)fluorodeoxyglucose positron emission tomography scan, fused to the CT to create a composite tumor volume. For IMRT and 3D-CRT, the target included the primary tumor and regional nodes either > or =1.0 cm in short-axis dimension on CT or with increased uptake on PET. For ENI, the target included the primary tumor plus the ipsilateral hilum and mediastinum from the inferior head of the clavicle to at least 5.0 cm below the carina. The goal was to deliver 70 Gy to > or =99% of the planning target volume (PTV) in 35 daily fractions (46 Gy to electively treated mediastinum) while meeting multiple normal-tissue dose constraints. Heterogeneity correction was applied to all dose calculations (maximum allowable heterogeneity within PTV 30%). Pulmonary and esophageal constraints were as follows: lung V(20) < or =25%, mean lung dose < or =15 Gy, esophagus V(50) < or =25%, mean esophageal dose < or =25 Gy. At the completion of all planning, the four techniques were contrasted for their ability to achieve the set dose constraints and deliver tumoricidal RT doses. Requiring a minimum dose of 70 Gy within the PTV, we found that IMRT was associated with a greater degree of heterogeneity within the target and, correspondingly, higher mean doses and tumor control probabilities (TCPs), 7%-8% greater than 3D-CRT and 14%-16% greater than ENI. Comparing the treatment techniques in this manner, we found only minor differences between 3D-CRT and IMRT, but clearly greater risks of pulmonary and esophageal toxicity with ENI. The mean lung V(20) was 36% with ENI vs. 23%-25% with the three other techniques, whereas the average mean lung dose was approximately 21.5 Gy (ENI) vs. 15.5 Gy (others). Similarly, the mean esophagus V(50) was doubled with ENI, to 34% rather than 15%-18%. To account for differences in heterogeneity, we also compared the techniques giving each plan a tumor control probability equivalent to that of the optimized 3D-CRT plan delivering 70 Gy. Using this method, IMRT and 3D-CRT offered similar results in node-negative cases (mean lung and esophageal normal-tissue complication probability [NTCP] of approximately 10% and 2%-7%, respectively), but ENI was distinctly worse (mean NTCPs of 29% and 20%). In node-positive cases, however, IMRT reduced the lung V(20) and mean dose by approximately 15% and lung NTCP by 30%, compared to 3D-CRT. Compared to ENI, the reductions were 50% and >100%. Again, for node-positive cases, especially where the gross tumor volume was close to the esophagus, IMRT reduced the mean esophagus V(50) by 40% (vs. 3D-CRT) to 145% (vs. ENI). The esophageal NTCP was at least doubled converting from IMRT to 3D-CRT and tripled converting from IMRT to ENI. Finally, the total number of fractions for each plan was increased or decreased until all outlined normal-tissue constraints were reached/satisfied. While meeting all constraints, IMRT or 3D-CRT increased the deliverable dose in node-negative patients by >200% over ENI. In node-positive patients, IMRT increased the deliverable dose 25%-30% over 3D-CRT and 130%-140% over ENI. The use of 3D-CRT without IMRT increased the deliverable RT dose >80% over ENI. Using a limited number of 3D-CRT beams decreased the lung V(20), mean dose, and NTCP in node-positive patients. The use of 3D-CRT, particul mean dose, and NTCP in node-positive patients. The use of 3D-CRT, particularly with only 3 to 4 beam angles, has the ability to reduce normal-tissue toxicity, but has limited potential for dose escalation beyond the current standard in node-positive patients. IMRT is of limited additional value (compared to 3D-CRT) in node-negative cases, but is beneficial in node-positive cases and in cases with target volumes close to the esophagus. When meeting all normal-tissue constraints in node-positive patients, IMRT can deliver RT doses 25%-30% greater than 3D-CRT and 130%-140% greater than ENI. Whereas the possibility of dose escalation is severely limited with ENI, the potential for pulmonary and esophageal toxicity is clearly increased.

Dose escalation can maximize therapeutic potential of sunitinib in patients with metastatic renal cell carcinoma.

PubMed

Maráz, Anikó; Cserháti, Adrienn; Uhercsák, Gabriella; Szilágyi, Éva; Varga, Zoltán; Révész, János; Kószó, Renáta; Varga, Linda; Kahán, Zsuzsanna

2018-03-15

In patients with metastatic renal cell cancer, based on limited evidence, increased sunitinib exposure is associated with better outcome. The survival and toxicity data of patients receiving individualized dose escalated sunitinib therapy as compared to standard management were analyzed in this study. From July 2013, the data of metastatic renal cell cancer patients with slight progression but still a stable disease according to RECIST 1.1 criteria treated with an escalated dose of sunitinib (first level: 62.5 mg/day in 4/2 or 2 × 2/1 scheme, second level: 75 mg/day in 4/2 or 2 × 2/1 scheme) were collected prospectively. Regarding characteristics, outcome, and toxicity data, an explorative retrospective analysis of the register was carried out, comparing treatments after and before July 1, 2013 in the study (selected patients for escalated dose) and control (standard dose) groups, respectively. The study involved 103 patients receiving sunitinib therapy with a median overall and progression free survival of 25.36 ± 2.62 and 14.2 ± 3.22 months, respectively. Slight progression was detected in 48.5% of them. First and second-level dose escalation were indicated in 18.2% and 4.1% of patients, respectively. The dosing scheme was modified in 22.2%. The median progression free survival (39.7 ± 5.1 vs 14.2 ± 1.3 months (p = 0.037)) and the overall survival (57.5 ± 10.7 vs 27.9 ± 2.5 months (p = 0.044)) were significantly better in the study group (with dose escalation) than in the control group. Patients with nephrectomy and lower Memorial Sloan Kettering Cancer Center (MSKCC) scores showed more favorable outcomes. After dose escalation, the most common adverse events were worsening or development of fatigue, hypertension, stomatitis, and weight loss of over 10%. Escalation of sunitinib dosing in selected patients with metastatic renal cell cancer, especially in case of slight progression, based on tolerable toxicity is safe and improves outcome. Dose escalation in 12.5 mg steps may be recommended for properly educated patients.

Dosimetric effect of beam arrangement for intensity-modulated radiation therapy in the treatment of upper thoracic esophageal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Yuchuan; Deng, Min; Zhou, Xiaojuan

To evaluate the lung sparing in intensity-modulated radiation therapy (IMRT) for patients with upper thoracic esophageal tumors extending inferiorly to the thorax by different beam arrangement. Overall, 15 patient cases with cancer of upper thoracic esophagus were selected for a retrospective treatment-planning study. Intensity-modulated radiation therapy plans using 4, 5, and 7 beams (4B, 5B, and 7B) were developed for each patient by direct machine parameter optimization (DMPO). All plans were evaluated with respect to dose volumes to irradiated targets and normal structures, with statistical comparisons made between 4B with 5B and 7B intensity-modulated radiation therapy plans. Differences among plansmore » were evaluated using a two-tailed Friedman test at a statistical significance of p < 0.05. The maximum dose, average dose, and the conformity index (CI) of planning target volume 1 (PTV1) were similar for 3 plans for each case. No significant difference of coverage for planning target volume 1 and maximum dose for spinal cords were observed among 3 plans in present study (p > 0.05). The average V{sub 5}, V{sub 13}, V{sub 20}, mean lung dose, and generalized equivalent uniform dose (gEUD) for the total lung were significantly lower in 4B-plans than those data in 5B-plans and 7B-plans (p < 0.01). Although the average V{sub 30} for the total lung were significantly higher in 4B-plans than those in 5B-plans and 7B-plans (p < 0.05). In addition, when comparing with the 4B-plans, the conformity/heterogeneity index of the 5B- and 7B-plans were significantly superior (p < 0.05). The 4B-intensity-modulated radiation therapy plan has advantage to address the specialized problem of lung sparing to low- and intermediate-dose exposure in the thorax when dealing with relative long tumors extended inferiorly to the thoracic esophagus for upper esophageal carcinoma with the cost for less conformity. Studies are needed to compare the superiority of volumetric modulated arc therapy with intensity-modulated radiation therapy technique.« less

Microscopy imaging system and method employing stimulated raman spectroscopy as a contrast mechanism

DOEpatents

Xie, Xiaoliang Sunney [Lexington, MA; Freudiger, Christian [Boston, MA; Min, Wei [Cambridge, MA

2011-09-27

A microscopy imaging system includes a first light source for providing a first train of pulses at a first center optical frequency .omega..sub.1, a second light source for providing a second train of pulses at a second center optical frequency .omega..sub.2, a modulator system, an optical detector, and a processor. The modulator system is for modulating a beam property of the second train of pulses at a modulation frequency f of at least 100 kHz. The optical detector is for detecting an integrated intensity of substantially all optical frequency components of the first train of pulses from the common focal volume by blocking the second train of pulses being modulated. The processor is for detecting, a modulation at the modulation frequency f, of the integrated intensity of the optical frequency components of the first train of pulses to provide a pixel of an image for the microscopy imaging system.

An accelerated dose escalation with a grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial.

PubMed

Chaker, A M; Al-Kadah, B; Luther, U; Neumann, U; Wagenmann, M

2015-01-01

The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation.

Improving Escalation of Care: Development and Validation of the Quality of Information Transfer Tool.

PubMed

Johnston, Maximilian J; Arora, Sonal; Pucher, Philip H; Reissis, Yannis; Hull, Louise; Huddy, Jeremy R; King, Dominic; Darzi, Ara

2016-03-01

To develop and provide validity and feasibility evidence for the QUality of Information Transfer (QUIT) tool. Prompt escalation of care in the setting of patient deterioration can prevent further harm. Escalation and information transfer skills are not currently measured in surgery. This study comprised 3 phases: the development (phase 1), validation (phase 2), and feasibility analysis (phase 3) of the QUIT tool. Phase 1 involved identification of core skills needed for successful escalation of care through literature review and 33 semistructured interviews with stakeholders. Phase 2 involved the generation of validity evidence for the tool using a simulated setting. Thirty surgeons assessed a deteriorating postoperative patient in a simulated ward and escalated their care to a senior colleague. The face and content validity were assessed using a survey. Construct and concurrent validity of the tool were determined by comparing performance scores using the QUIT tool with those measured using the Situation-Background-Assessment-Recommendation (SBAR) tool. Phase 3 was conducted using direct observation of escalation scenarios on surgical wards in 2 hospitals. A 7-category assessment tool was developed from phase 1 consisting of 24 items. Twenty-one of 24 items had excellent content validity (content validity index >0.8). All 7 categories and 18 of 24 (P < 0.05) items demonstrated construct validity. The correlation between the QUIT and SBAR tools used was strong indicating concurrent validity (r = 0.694, P < 0.001). Real-time scoring of escalation referrals was feasible and indicated that doctors currently have better information transfer skills than nurses when faced with a deteriorating patient. A validated tool to assess information transfer for deteriorating surgical patients was developed and tested using simulation and real-time clinical scenarios. It may improve the quality and safety of patient care on the surgical ward.

Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

PubMed Central

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Aim Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID:27274277

Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

PubMed

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3-6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered.

Observational evidence that urbanisation and neighbourhood deprivation are associated with escalation in chronic pharmacological pain treatment: a longitudinal population-based study in the Netherlands.

PubMed

Leue, Carsten; Buijs, Servaas; Strik, Jacqueline; Lousberg, Richel; Smit, Jasper; van Kleef, Maarten; van Os, Jim

2012-01-01

To examine, in the light of the association between urban environment and poor mental health, whether urbanisation and neighbourhood deprivation are associated with analgesic escalation in chronic pharmacological pain treatment and whether escalation is associated with prescriptions of psychotropic medication. Longitudinal analysis of a population-based routine dispensing database in the Netherlands. Representative sample of pharmacies, covering 73% of the Dutch nationwide medication consumption in the primary care and hospital outpatient settings. 449 410 patients aged 15-85 years were included, of whom 166 374 were in the Starter group and 283 036 in the Continuation group of chronic analgesic treatment. Escalation of analgesics (ie, change to a higher level of analgesic potency, classified across five levels) in association with urbanisation (five levels) and dichotomous neighbourhood deprivation was analysed over a 6-month observation period. Ordered logistic multivariate model evaluating analgesic treatment. In both Starter and Continuation groups, escalation was positively associated with urbanisation in a dose-response fashion (Starter group: OR (urbanisation level 1 compared with level 5): 1.24, 95% CI 1.18 to 1.30; Continuation group: OR 1.18, 95% CI 1.14 to 1.23). An additional association was apparent with neighbourhood deprivation (Starter group: OR 1.07, 95% CI 1.02 to 1.11; Continuation group: OR 1.04, 95% CI 1.01 to 1.08). Use of somatic and particularly psychotropic co-medication was associated with escalation in both groups. Escalation of chronic analgesic treatment is associated with urban and deprived environments and occurs in a context of adding psychotropic medication prescriptions. These findings suggest that pain outcomes and mental health outcomes share factors that increase risk and remedy suffering.

Escalation to Major Depressive Disorder among adolescents with subthreshold depressive symptoms: evidence of distinct subgroups at risk.

PubMed

Hill, Ryan M; Pettit, Jeremy W; Lewinsohn, Peter M; Seeley, John R; Klein, Daniel N

2014-04-01

The presence of subthreshold depressive symptoms (SubD) in adolescence is associated with high prospective risk of developing Major Depressive Disorder (MDD). Little is known about variables that predict escalation from SubD to MDD. This study used a longitudinal prospective design in a community sample of adolescents to identify combinations of risk factors that predicted escalation from SubD to MDD. Classification tree analysis was used to identify combinations of risk factors that improved the sensitivity and specificity of prediction of MDD onset among 424 adolescents with a lifetime history of SubD. Of the 424, 144 developed MDD during the follow-up period. Evidence for multiple subgroups was found: among adolescents with poor friend support, the highest risk of escalation was among participants with lifetime histories of an anxiety or substance use disorder. Among adolescents with high friend support, those reporting multiple major life events in the past year or with a history of an anxiety disorder were at highest risk of escalation. Study findings may not inform prevention efforts for individuals who first develop SubD during adulthood. This study did not examine the temporal ordering of predictors involved in escalation from SubD to MDD. Adolescents with a history of SubD were at highest risk of escalation to MDD in the presence of poor friend support and an anxiety or substance use disorder, or in the presence of better friend support, multiple major life events, and an anxiety disorder. Findings may inform case identification approaches for adolescent depression prevention programs. Copyright © 2014 Elsevier B.V. All rights reserved.

Dose-per-fraction escalation of accelerated hypofractionated three-dimensional conformal radiotherapy in locally advanced non-small cell lung cancer.

PubMed

Kepka, Lucyna; Tyc-Szczepaniak, Dobromira; Bujko, Krzysztof

2009-07-01

To determine the efficacy of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small cell lung cancer (NSCLC). Between 2001 and 2007, 173 patients with stage III NSCLC were treated using accelerated 3D-CRT and the simultaneous boost technique. Initially, the total dose of 56.7 Gy (including 39.9 Gy to the elective area) was delivered over 4 weeks in fractions of 2.7 Gy (1.9 Gy to the elective area). The dose-per-fraction escalation study commenced after the outcomes of 70 patients had been evaluated. The dose per fraction was increased from 2.7 through 2.8 Gy (level 1 escalation) to 2.9 Gy (level 2 escalation); the total dose increased, respectively, from 56.7 Gy through 58.8 Gy to 60.9 Gy. The dose to the elective area and the overall treatment time remained unchanged. Fit patients received two to three courses of chemotherapy before radiotherapy. The 2- and 3-year overall survival rates were 32 and 19%, respectively (median survival = 17 months). Of the patients, 7% had grade III acute esophageal toxicity and 6% had grade III or greater late pulmonary toxicity. Two of the nine patients who received the level 2 escalation (60.9 Gy) died of pulmonary toxicity. The study was terminated at a dose of 58.8 Gy and this schema was adopted as the institutional policy for treatment of stage III NSCLC. Although dose escalation with accelerated hypofractionated 3D-CRT was limited, the results and toxicity profiles obtained using this technique are promising.

Digital micromirror device camera with per-pixel coded exposure for high dynamic range imaging.

PubMed

Feng, Wei; Zhang, Fumin; Wang, Weijing; Xing, Wei; Qu, Xinghua

2017-05-01

In this paper, we overcome the limited dynamic range of the conventional digital camera, and propose a method of realizing high dynamic range imaging (HDRI) from a novel programmable imaging system called a digital micromirror device (DMD) camera. The unique feature of the proposed new method is that the spatial and temporal information of incident light in our DMD camera can be flexibly modulated, and it enables the camera pixels always to have reasonable exposure intensity by DMD pixel-level modulation. More importantly, it allows different light intensity control algorithms used in our programmable imaging system to achieve HDRI. We implement the optical system prototype, analyze the theory of per-pixel coded exposure for HDRI, and put forward an adaptive light intensity control algorithm to effectively modulate the different light intensity to recover high dynamic range images. Via experiments, we demonstrate the effectiveness of our method and implement the HDRI on different objects.

Reproducible deep-inspiration breath-hold irradiation with forward intensity-modulated radiotherapy for left-sided breast cancer significantly reduces cardiac radiation exposure compared to inverse intensity-modulated radiotherapy.

PubMed

Bolukbasi, Yasemin; Saglam, Yucel; Selek, Ugur; Topkan, Erkan; Kataria, Anglina; Unal, Zeynep; Alpan, Vildan

2014-01-01

To investigate the objective utility of our clinical routine of reproducible deep-inspiration breath-hold irradiation for left-sided breast cancer patients on reducing cardiac exposure. Free-breathing and reproducible deep-inspiration breath-hold scans were evaluated for our 10 consecutive left-sided breast cancer patients treated with reproducible deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated radiotherapy plans were generated for each computed tomography dataset. Reproducible deep-inspiration breath-hold plans with forward intensity-modulated radiotherapy significantly spared the heart and left anterior descending artery compared to generated free-breathing plans based on mean doses - free-breathing vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy, P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66 cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P = 0.007) - whereas they revealed no additional burden on the ipsilateral lung. Reproducible deep-inspiration breath-hold and free-breathing plans with inverse intensity-modulated radiotherapy provided similar organ at risk sparing by reducing the mean doses to the left ventricle, left anterior descending artery, heart, V10-V20 of the heart and right ventricle. However, forward intensity-modulated radiotherapy showed significant reduction in doses to the left ventricle, left anterior descending artery, heart, right ventricle, and contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses for free-breathing vs reproducible deep-inspiration breath-hold of the proximal left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50 Gy isodose line of the proximal left anterior descending artery were 6.6 vs 3.3 cm and of the distal left anterior descending artery were 7.4 vs 4.1 cm, with forward intensity-modulated radiotherapy. Overall reduction in mean doses to proximal and distal left anterior descending artery with deep-inspiration breath-hold irradiation was 39% (P = 0.02) and 52% (P = 0.002), respectively. We found a significant reduction of radiation exposure to the contralateral breast, left and right ventricles, as well as of proximal and especially distal left anterior descending artery with the deep-inspiration breath-hold technique with forward intensity-modulated radiotherapy planning.

Acoustic characteristics of simulated respiratory-induced vocal tremor.

PubMed

Lester, Rosemary A; Story, Brad H

2013-05-01

The purpose of this study was to investigate the relation of respiratory forced oscillation to the acoustic characteristics of vocal tremor. Acoustical analyses were performed to determine the characteristics of the intensity and fundamental frequency (F0) for speech samples obtained by Farinella, Hixon, Hoit, Story, and Jones (2006) using a respiratory forced oscillation paradigm with 5 healthy adult males to simulate vocal tremor involving respiratory pressure modulation. The analyzed conditions were sustained productions of /a/ with amplitudes of applied pressure of 0, 1, 2, and 4 cmH2O and a rate of 5 Hz. Forced oscillation of the respiratory system produced modulation of the intensity and F0 for all participants. Variability was observed between participants and conditions in the change in intensity and F0 per unit of pressure change, as well as in the mean intensity and F0. However, the extent of modulation of intensity and F0 generally increased as the applied pressure increased, as would be expected. These findings suggest that individuals develop idiosyncratic adaptations to pressure modulations, which are important to understanding aspects of variability in vocal tremor, and highlight the need to assess all components of the speech mechanism that may be directly or indirectly affected by tremor.

Fan-beam intensity modulated proton therapy.

PubMed

Hill, Patrick; Westerly, David; Mackie, Thomas

2013-11-01

This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques. A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0-255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets. Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal falloff of a proton depth-dose distribution was found to provide sufficient control over the dose distribution to meet objectives, even with coarse lateral resolution and channel widths as large as 2 cm. Treatment plans on both phantom and patient data show that dose conformity suffers when treatments are delivered from less than approximately ten angles. Treatment time for a sample prostate delivery is estimated to be on the order of 10 min, and neutron production is estimated to be comparable to that found for existing collimated systems. Fan beam proton therapy is a method of delivering intensity modulated proton therapy which may be employed as an alternative to magnetic scanning systems. A fan beam of protons can be created by a set of quadrupole magnets and modified by a dual-purpose range and intensity modulator. This can be used to deliver inversely planned treatments, with spot intensities optimized to meet user defined dose objectives. Additionally, the ability of a fan beam delivery system to effectively treat multiple beam spots simultaneously may provide advantages as compared to spot scanning deliveries.

Dangerous Thresholds. Managing Escalation in the 21st Century

DTIC Science & Technology

2008-01-01

Escalation in the 21st Century Forrest E . Morgan n Karl P. Mueller Evan S. Medeiros n Kevin L. Pollpeter n Roger Cliff Dangerous Thresholds The RAND...impacts of U.S. policy in the current security envi- ronment: War and Escalation in South Asia, by John E . Peters, James Dickens, Derek Eaton, C...Striking First: Preemptive and Preventive Attack in U.S. National Security Policy, by Karl P. Muel- ler, Jasen J. Castillo, Forrest E . Morgan, Negeen

Treatment-related mortality in patients with advanced-stage hodgkin lymphoma: an analysis of the german hodgkin study group.

PubMed

Wongso, Diana; Fuchs, Michael; Plütschow, Annette; Klimm, Beate; Sasse, Stephanie; Hertenstein, Bernd; Maschmeyer, Georg; Vieler, Tom; Dührsen, Ulrich; Lindemann, Walter; Aulitzky, Walter; Diehl, Volker; Borchmann, Peter; Engert, Andreas

2013-08-01

The introduction of BEACOPP(escalated) (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPP(escalated). In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPP(escalated)-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15. Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPP(escalated) (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%. The individual risk of TRM associated with BEACOPP(escalated) can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.

Conflict escalation in paediatric services: findings from a qualitative study.

PubMed

Forbat, Liz; Teuten, Bea; Barclay, Sarah

2015-08-01

To explore clinician and family experiences of conflict in paediatric services, in order to map the trajectory of conflict escalation. Qualitative interview study, employing extreme-case sampling. Interviews were analysed using an iterative thematic approach to identify common themes regarding the experience and escalation of conflict. Thirty-eight health professionals and eight parents. All participants had direct experience of conflict, including physical assault and court proceedings, at the interface of acute and palliative care. Two teaching hospitals, one district general hospital and two paediatric hospices in England, in 2011. Conflicts escalate in a predictable manner. Clearly identifiable behaviours by both clinicians and parents are defined as mild, moderate and severe. Mild describes features like the insensitive use of language and a history of unresolved conflict. Moderate involves a deterioration of trust, and a breakdown of communication and relationships. Severe marks disintegration of working relationships, characterised by behavioural changes including aggression, and a shift in focus from the child's best interests to the conflict itself. Though conflicts may remain at one level, those which escalated tended to move sequentially from one level to the next. Understanding how conflicts escalate provides clinicians with a practical, evidence-based framework to identify the warning signs of conflict in paediatrics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Signal analysis and spectrum distortion correction for tunable diode laser absorption spectroscopy system].

PubMed

Bao, Wei-Yi; Zhu, Yong; Chen, Jun; Chen, Jun-Qing; Liang, Bo

2011-04-01

In the present paper, the signal of a tunable diode laser absorption spectroscopy (TDLAS) trace gas sensing system, which has a wavelength modulation with a wide range of modulation amplitudes, is studied based on Fourier analysis method. Theory explanation of spectrum distortion induced by laser intensity amplitude modulation is given. In order to rectify the spectrum distortion, a method of synchronous amplitude modulation suppression by a variable optical attenuator is proposed. To validate the method, an experimental setup is designed. Absorption spectrum measurement experiments on CO2 gas were carried out. The results show that the residual laser intensity modulation amplitude of the experimental system is reduced to -0.1% of its original value and the spectrum distortion improvement is 92% with the synchronous amplitude modulation suppression. The modulation amplitude of laser intensity can be effectively reduced and the spectrum distortion can be well corrected by using the given correction method and system. By using a variable optical attenuator in the TDLAS (tunable diode laser absorption spectroscopy) system, the dynamic range requirements of photoelectric detector, digital to analog converter, filters and other aspects of the TDLAS system are reduced. This spectrum distortion correction method can be used for online trace gas analyzing in process industry.

Detection of a Novel Mechanism of Acousto-Optic Modulation of Incoherent Light

PubMed Central

Jarrett, Christopher W.; Caskey, Charles F.; Gore, John C.

2014-01-01

A novel form of acoustic modulation of light from an incoherent source has been detected in water as well as in turbid media. We demonstrate that patterns of modulated light intensity appear to propagate as the optical shadow of the density variations caused by ultrasound within an illuminated ultrasonic focal zone. This pattern differs from previous reports of acousto-optical interactions that produce diffraction effects that rely on phase shifts and changes in light directions caused by the acoustic modulation. Moreover, previous studies of acousto-optic interactions have mainly reported the effects of sound on coherent light sources via photon tagging, and/or the production of diffraction phenomena from phase effects that give rise to discrete sidebands. We aimed to assess whether the effects of ultrasound modulation of the intensity of light from an incoherent light source could be detected directly, and how the acoustically modulated (AOM) light signal depended on experimental parameters. Our observations suggest that ultrasound at moderate intensities can induce sufficiently large density variations within a uniform medium to cause measurable modulation of the intensity of an incoherent light source by absorption. Light passing through a region of high intensity ultrasound then produces a pattern that is the projection of the density variations within the region of their interaction. The patterns exhibit distinct maxima and minima that are observed at locations much different from those predicted by Raman-Nath, Bragg, or other diffraction theory. The observed patterns scaled appropriately with the geometrical magnification and sound wavelength. We conclude that these observed patterns are simple projections of the ultrasound induced density changes which cause spatial and temporal variations of the optical absorption within the illuminated sound field. These effects potentially provide a novel method for visualizing sound fields and may assist the interpretation of other hybrid imaging methods. PMID:25105880

Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hafeez, Shaista, E-mail: Shaista.Hafeez@icr.ac.uk; The Royal Marsden National Health Service Foundation Trust, London; Warren-Oseni, Karole

Purpose: Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue. Methods and Materials: A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A “plan of the day” approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction fillingmore » and coverage. Results: A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D{sub 98} (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy. Conclusions: Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be evaluated in a randomized trial.« less

Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis.

PubMed

Cooperberg, Matthew R; Ramakrishna, Naren R; Duff, Steven B; Hughes, Kathleen E; Sadownik, Sara; Smith, Joseph A; Tewari, Ashutosh K

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Multiple treatment alternatives exist for localised prostate cancer, with few high-quality studies directly comparing their comparative effectiveness and costs. The present study is the most comprehensive cost-effectiveness analysis to date for localised prostate cancer, conducted with a lifetime horizon and accounting for survival, health-related quality-of-life, and cost impact of secondary treatments and other downstream events, as well as primary treatment choices. The analysis found minor differences, generally slightly favouring surgical methods, in quality-adjusted life years across treatment options. However, radiation therapy (RT) was consistently more expensive than surgery, and some alternatives, e.g. intensity-modulated RT for low-risk disease, were dominated - that is, both more expensive and less effective than competing alternatives. To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model. A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis. Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6-10.5 for intermediate-risk patients and 7.8-9.3 for high-risk patients. There were no statistically significant differences among surgical methods, which tended to be more effective than RT methods, with the exception of combined external beam + brachytherapy for high-risk disease. RT methods were consistently more expensive than surgical methods; costs ranged from $19 901 (robot-assisted prostatectomy for low-risk disease) to $50 276 (combined RT for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions about strategies to improve efficiency of treatment selection for localised prostate cancer. © 2012 BJU International.

Total quality management in the hospital setting.

PubMed

Ernst, D F

1994-01-01

With the increasing demands on hospitals for improved quality and lower costs, hospitals have been forced to reevaluate their manner of operation and quality assurance (QA) programs. Hospitals have been faced with customer dissatisfaction with services, escalating costs, intense competition, and reduced reimbursement for services. As a result, many hospitals have incorporated total quality management (TQM), also known as continuous quality improvement (CQI) and quality improvement (QI), to improve quality care and decrease costs. This article examines the concept of TQM, its rationale, and how it can be implemented in a hospital. A comparison of TQM and QA is made. Examples of hospital implementation of TQM and problems and issues associated with TQM in the hospital setting are explored.

Age-related effects of chronic restraint stress on ethanol drinking, ethanol-induced sedation, and on basal and stress-induced anxiety response

PubMed Central

Fernández, Macarena Soledad; Fabio, María Carolina; Miranda-Morales, Roberto Sebastián; Virgolini, Miriam B.; De Giovanni, Laura N.; Hansen, Cristian; Wille-Bille, Aranza; Nizhnikov, Michael E.; Spear, Linda P.; Pautassi, Ricardo Marcos

2016-01-01

Adolescents are sensitive to the anxiolytic effect of ethanol, and evidence suggests that they may be more sensitive to stress than adults. Relatively little is known, however, about age-related differences in stress modulation of ethanol drinking or stress modulation of ethanol-induced sedation and hypnosis. We observed that chronic restraint stress transiently exacerbated free-choice ethanol drinking in adolescent, but not in adult, rats. Restraint stress altered exploration patterns of a light-dark box apparatus in adolescents and adults. Stressed animals spent significantly more time in the white area of the maze and made significantly more transfers between compartments than their non-stressed peers. Behavioral response to acute stress, on the other hand, was modulated by prior restraint stress only in adults. Adolescents, unlike adults, exhibited ethanol-induced motor stimulation in an open field. Stress increased the duration of loss of the righting reflex after a high ethanol dose, yet this effect was similar at both ages. Ethanol-induced sleep time was much higher in adult than in adolescent rats, yet stress diminished ethanol-induced sleep time only in adults. The study indicates age-related differences that may increase the risk for initiation and escalation in alcohol drinking. PMID:26830848

An investigation into the effects of frequency-modulated transcutaneous electrical nerve stimulation (TENS) on experimentally-induced pressure pain in healthy human participants.

PubMed

Chen, Chih-Chung; Johnson, Mark I

2009-10-01

Frequency-modulated transcutaneous electrical nerve stimulation (TENS) delivers currents that fluctuate between preset boundaries over a fixed period of time. This study compared the effects of constant-frequency TENS and frequency-modulated TENS on blunt pressure pain in healthy human volunteers. Thirty-six participants received constant-frequency TENS (80 pps), frequency-modulated TENS (20 to 100 pps), and placebo (no current) TENS at a strong nonpainful intensity in a randomized cross-over manner. Pain threshold was taken from the forearm using pressure algometry. There were no statistical differences between constant-frequency TENS and frequency-modulated TENS after 20 minutes (OR = 1.54; CI, 0.29, 8.23, P = 1.0). Both constant-frequency TENS and frequency-modulated TENS were superior to placebo TENS (OR = 59.5, P < .001 and OR = 38.5, P < .001, respectively). Frequency-modulated TENS does not influence hypoalgesia to any greater extent than constant-frequency TENS when currents generate a strong nonpainful paraesthesia at the site of pain. The finding that frequency-modulated TENS and constant-frequency TENS were superior to placebo TENS provides further evidence that a strong yet nonpainful TENS intensity is a prerequisite for hypoalgesia. This study provides evidence that TENS, delivered at a strong nonpainful intensity, increases pain threshold to pressure algometry in healthy participants over and above that seen with placebo (no current) TENS. Frequency-modulated TENS does not increase hypoalgesia to any appreciable extent to that seen with constant-frequency TENS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Joe Y., E-mail: jychang@mdanderson.org; Jabbour, Salma K.; De Ruysscher, Dirk

Radiation dose escalation has been shown to improve local control and survival in patients with non–small cell lung cancer in some studies, but randomized data have not supported this premise, possibly owing to adverse effects. Because of the physical characteristics of the Bragg peak, proton therapy (PT) delivers minimal exit dose distal to the target volume, resulting in better sparing of normal tissues in comparison to photon-based radiation therapy. This is particularly important for lung cancer given the proximity of the lung, heart, esophagus, major airways, large blood vessels, and spinal cord. However, PT is associated with more uncertainty becausemore » of the finite range of the proton beam and motion for thoracic cancers. PT is more costly than traditional photon therapy but may reduce side effects and toxicity-related hospitalization, which has its own associated cost. The cost of PT is decreasing over time because of reduced prices for the building, machine, maintenance, and overhead, as well as newer, shorter treatment programs. PT is improving rapidly as more research is performed particularly with the implementation of 4-dimensional computed tomography–based motion management and intensity modulated PT. Given these controversies, there is much debate in the oncology community about which patients with lung cancer benefit significantly from PT. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group intends to address the issues of PT indications, advantages and limitations, cost-effectiveness, technology improvement, clinical trials, and future research directions. This consensus report can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions.« less

Radiobiological Impact of Reduced Margins and Treatment Technique for Prostate Cancer in Terms of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Ingelise, E-mail: inje@rn.d; Carl, Jesper; Lund, Bente

2011-07-01

Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on themore » Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications.« less

Esophageal cancer dose escalation using a simultaneous integrated boost technique.

PubMed

Welsh, James; Palmer, Matthew B; Ajani, Jaffer A; Liao, Zhongxing; Swisher, Steven G; Hofstetter, Wayne L; Allen, Pamela K; Settle, Steven H; Gomez, Daniel; Likhacheva, Anna; Cox, James D; Komaki, Ritsuko

2012-01-01

We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation. Copyright © 2012 Elsevier Inc. All rights reserved.

Esophageal Cancer Dose Escalation using a Simultaneous Integrated Boost Technique

PubMed Central

Welsh, James; Palmer, Matthew B.; Ajani, Jaffer A.; Liao, Zhongxing; Swisher, Steven G.; Hofstetter, Wayne L.; Allen, Pamela K.; Settle, Steven H.; Gomez, Daniel; Likhacheva, Anna; Cox, James D.; Komaki, Ritsuko

2014-01-01

Purpose We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Methods and Materials Treatment plans were generated using four different approaches (two-dimensional conformal RT [2D-CRT] to 50.4 Gy or 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. Results The 50.4-Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4-Gy 2D-CRT plan. The 64.8-Gy SIB-IMRT plan produced a 28% increase in GTV dose and the same normal tissue doses as the 50.4-Gy IMRT plan; compared with the 50.4-Gy 2D-CRT plan, the 64.8-Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). Conclusions The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation. PMID:21123005

Impact of gastric filling on radiation dose delivered to gastroesophageal junction tumors.

PubMed

Bouchard, Myriam; McAleer, Mary Frances; Starkschall, George

2010-05-01

This study examined the impact of gastric filling variation on target coverage of gastroesophageal junction (GEJ) tumors in three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), or IMRT with simultaneous integrated boost (IMRT-SIB) plans. Eight patients previously receiving radiation therapy for esophageal cancer had computed tomography (CT) datasets acquired with full stomach (FS) and empty stomach (ES). We generated treatment plans for 3DCRT, IMRT, or IMRT-SIB for each patient on the ES-CT and on the FS-CT datasets. The 3DCRT and IMRT plans were planned to 50.4 Gy to the clinical target volume (CTV), and the same for IMRT-SIB plus 63.0 Gy to the gross tumor volume (GTV). Target coverage was evaluated using dose-volume histogram data for patient treatments simulated with ES-CT sets, assuming treatment on an FS for the entire course, and vice versa. FS volumes were a mean of 3.3 (range, 1.7-7.5) times greater than ES volumes. The volume of the GTV receiving >or=50.4 Gy (V(50.4Gy)) was 100% in all situations. The planning GTV V(63Gy) became suboptimal when gastric filling varied, regardless of whether simulation was done on the ES-CT or the FS-CT set. Stomach filling has a negligible impact on prescribed dose delivered to the GEJ GTV, using either 3DCRT or IMRT planning. Thus, local relapses are not likely to be related to variations in gastric filling. Dose escalation for GEJ tumors with IMRT-SIB may require gastric filling monitoring.

Interferometric millimeter wave and THz wave doppler radar

DOEpatents

Liao, Shaolin; Gopalsami, Nachappa; Bakhtiari, Sasan; Raptis, Apostolos C.; Elmer, Thomas

2015-08-11

A mixerless high frequency interferometric Doppler radar system and methods has been invented, numerically validated and experimentally tested. A continuous wave source, phase modulator (e.g., a continuously oscillating reference mirror) and intensity detector are utilized. The intensity detector measures the intensity of the combined reflected Doppler signal and the modulated reference beam. Rigorous mathematics formulas have been developed to extract bot amplitude and phase from the measured intensity signal. Software in Matlab has been developed and used to extract such amplitude and phase information from the experimental data. Both amplitude and phase are calculated and the Doppler frequency signature of the object is determined.

Effects of digital phase-conjugate light intensity on time-reversal imaging through animal tissue.

PubMed

Toda, Sogo; Kato, Yuji; Kudo, Nobuki; Shimizu, Koichi

2018-04-01

For transillumination imaging of animal tissues, we have attempted to suppress the scattering effect in a turbid medium using the time-reversal principle of phase-conjugate light. We constructed a digital phase-conjugate system to enable intensity modulation and phase modulation. Using this system, we clarified the effectiveness of the intensity information for restoration of the original light distribution through a turbid medium. By varying the scattering coefficient of the medium, we clarified the limit of time-reversal ability with intensity information of the phase-conjugate light. Experiment results demonstrated the applicability of the proposed technique to animal tissue.

Infrasound induced instability by modulation of condensation process in the atmosphere.

PubMed

Naugolnykh, Konstantin; Rybak, Samuil

2008-12-01

A sound wave in supersaturated water vapor can modulate both the process of heat release caused by condensation, and subsequently, as a result, the resonance interaction of sound with the modulated heat release provides sound amplification. High-intensity atmospheric perturbations such as cyclones and thunderstorms generate infrasound, which is detectable at large distances from the source. The wave-condensation instability can lead to variation in the level of infrasound radiation by a developing cyclone, and this can be as a precursor of these intense atmospheric events.

Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition.

PubMed

Kawashima, Mitsuhiko; Ariji, Takaki; Kameoka, Satoru; Ueda, Takashi; Kohno, Ryosuke; Nishio, Teiji; Arahira, Satoko; Motegi, Atsushi; Zenda, Sadamoto; Akimoto, Tetsuo; Tahara, Makoto; Hayashi, Ryuichi

2013-12-01

The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. One local recurrence was observed at Meckel's cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

Avoiding escalation from play to aggression in adult male rats: The role of ultrasonic calls.

PubMed

Burke, Candace J; Kisko, Theresa M; Pellis, Sergio M; Euston, David R

2017-11-01

Play fighting is most commonly associated with juvenile animals, but in some species, including rats, it can continue into adulthood. Post-pubertal engagement in play fighting is often rougher and has an increased chance of escalation to aggression, making the use of play signals to regulate the encounter more critical. During play, both juvenile and adult rats emit many 50-kHz calls and some of these may function as play facilitating signals. In the present study, unfamiliar adult male rats were introduced in a neutral enclosure and their social interactions were recorded. While all pairs escalated their playful encounters to become rougher, only the pairs in which one member was devocalized escalated to serious biting. A Monte Carlo shuffling technique was used for the analysis of the correlations between the overt playful and aggressive actions performed and the types and frequencies of various 50-kHz calls that were emitted. The analysis revealed that lower frequency (20-30kHz) calls with a flat component maybe particularly critical for de-escalating encounters and so allowing play to continue. Moreover, coordinating calls reciprocally, with either the same call mimicked in close, temporal association or with complementary calls emitted by participants as they engage in complementary actions (e.g., attacking the nape, being attacked on the nape), appeared to be ways with which calls could be potentially used to avoid escalation to aggression and so sustain playful interactions. Copyright © 2017 Elsevier B.V. All rights reserved.

Measuring the incentive value of escalating doses of heroin in heroin-dependent Fischer rats during acute spontaneous withdrawal

PubMed Central

Reed, Brian; Ho, Ann; Kreek, Mary Jeanne

2011-01-01

Rationale/objectives Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin’s incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence. Methods Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals’ behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded. Results Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs. Conclusions Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior. PMID:21748254

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beltran, C; Kamal, H

Purpose: To provide a multicriteria optimization algorithm for intensity modulated radiation therapy using pencil proton beam scanning. Methods: Intensity modulated radiation therapy using pencil proton beam scanning requires efficient optimization algorithms to overcome the uncertainties in the Bragg peaks locations. This work is focused on optimization algorithms that are based on Monte Carlo simulation of the treatment planning and use the weights and the dose volume histogram (DVH) control points to steer toward desired plans. The proton beam treatment planning process based on single objective optimization (representing a weighted sum of multiple objectives) usually leads to time-consuming iterations involving treatmentmore » planning team members. We proved a time efficient multicriteria optimization algorithm that is developed to run on NVIDIA GPU (Graphical Processing Units) cluster. The multicriteria optimization algorithm running time benefits from up-sampling of the CT voxel size of the calculations without loss of fidelity. Results: We will present preliminary results of Multicriteria optimization for intensity modulated proton therapy based on DVH control points. The results will show optimization results of a phantom case and a brain tumor case. Conclusion: The multicriteria optimization of the intensity modulated radiation therapy using pencil proton beam scanning provides a novel tool for treatment planning. Work support by a grant from Varian Inc.« less

Does high antibiotic consumption still reflect bad practices?

PubMed

Levent, T; Delfosse, F; Lambiotte, F; Dezorzi, S; Gosteau, L; Vasseur, M

2012-07-01

The authors had for aim to assess the quality of antibiotic prescription in an intensive care unit because of their high rate of consumption. A prospective 5-month study was made of the first 50 prescriptions of ciprofloxacin, levofloxacin, teicoplanin, vancomycin, and imipenem. Treatment was considered adequate at day 5 if the indication was relevant, with the right doses, and if the prescription was adapted to the antibiogram. Fifty treatments were evaluated (38 patients included). Eighty-four percent (42/50) was adequate at day 5. Glycopeptides and fluoroquinolones accounted for 2/3 of prescriptions. The absence of de-escalation was the most common mistake. The severity of presentations was evident with a mean SSI at 68 (22-113), and a mean BMI at 28 (18.5 - 50). Eighty-four percent (32/38) of patients were exposed to invasive devices, 47% died in the ICU. Most prescriptions were adequate. The patient profile could explain the high rate of antibiotic consumption. Bacteriological monitoring revealed an increased prevalence of resistant bacteria, which could explain a high rate of consumption along with adaptation of the dose to overweight. De-escalation, using aminosides more frequently, and shorter prescribed courses of fluoroquinolones should improve consumption rates does not always reflect bad practices, but may be adequate when considering bacterial ecology and patient profile. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Dynamical heat transport amplification in a far-field thermal transistor of VO{sub 2} excited with a laser of modulated intensity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ordonez-Miranda, Jose, E-mail: jose.ordonez@cnrs.pprime.fr; Ezzahri, Younès; Drevillon, Jérémie

2016-05-28

Far-field radiative heat transport in a thermal transistor made up of a vanadium dioxide base excited with a laser of modulated intensity is analytically studied and optimized. This is done by solving the equation of energy conservation for the steady-state and modulated components of the temperature and heat fluxes that the base exchanges with the collector and emitter. The thermal bistability of VO{sub 2} is used to find an explicit condition on the laser intensity required to maximize these heat fluxes to values higher than the incident flux. For a 1 μm-thick base heated with a modulation frequency of 0.5 Hz, itmore » is shown that both the DC and AC components of the heat fluxes are about 4 times the laser intensity, while the AC temperature remains an order of magnitude smaller than the DC one at around 343 K. Higher AC heat fluxes are obtained for thinner bases and/or lower frequencies. Furthermore, we find that out of the bistability temperatures associated with the dielectric-to-metal and metal-to-dielectric transitions of VO{sub 2}, the amplification of the collector-to-base and base-to-emitter heat fluxes is still possible, but at modulation frequencies lower than 0.1 Hz.« less

Intensity position modulation for free-space laser communication system

NASA Astrophysics Data System (ADS)

Jangjoo, Alireza; Faghihi, F.

2004-12-01

In this research a novel modulation technique for free-space laser communication system called Intensity Position Modulation (IPM) is carried out. According to TEM00 mode of a laser beam and by linear fitting on the Gaussian function as an approximation, the variation of linear part on the reverse biased pn photodiode produced alternating currents which contain the information. Here, no characteristic property of the beam as intensity or frequency is changed and only the beam position moves laterally. We demonstrated that in this method no bandwidth is required, so it is possible to reduce the background radiation noise by narrowband filtering of the carrier. The fidelity of the analog voice communication system which is made upon the IPM is satisfactory and we are able to transmit the audio signals up to 1Km.

Application of plasma gas modulation technique for improvement of the measurement of Mn emission intensity in ICP-AES.

PubMed

Kubota, K; Wagatsuma, K

2001-01-02

A phase-sensitive detection technique associated with a digital lock-in amplifier was applied for an improvement of the detection in ICP-AES. The lock-in amplifier works as an extremely narrow band pass filter. It can pick up the modulated signal, which has the same frequency as the reference signal, from any noise and thus it can improve the signal-to-noise ratio. Modulation of the ICP can be performed by mixing small amounts of air to argon as the outer gas cyclically, because the emission intensities of ionic lines are enhanced by using the mixed gas. An electromagnetic valve, which is placed in the outer-gas flow path, causes periodic variation in the air gas in the outer-gas flow, and thus switching the valve on/off can modulate the ICP. By choosing the appropriate conditions, the addition of air gas enhances the emission intensity of ionic lines more than that of the background, thus leading to improved signal-to-background ratios. At the same time the lock-in amplifier further enhances the ionic emissions because it picks up only the modulated part of the signal. By applying the plasma gas flow modulation technique the detection and the determination limits of the Mn II 257.610 nm line are improved in comparison with the conventional method. A change in plasma shape corresponding to the modulation frequency is observed when the ICP is modulated.

Escalator: An Autonomous Scheduling Scheme for Convergecast in TSCH

PubMed Central

Oh, Sukho; Hwang, DongYeop; Kim, Ki-Hyung; Kim, Kangseok

2018-01-01

Time Slotted Channel Hopping (TSCH) is widely used in the industrial wireless sensor networks due to its high reliability and energy efficiency. Various timeslot and channel scheduling schemes have been proposed for achieving high reliability and energy efficiency for TSCH networks. Recently proposed autonomous scheduling schemes provide flexible timeslot scheduling based on the routing topology, but do not take into account the network traffic and packet forwarding delays. In this paper, we propose an autonomous scheduling scheme for convergecast in TSCH networks with RPL as a routing protocol, named Escalator. Escalator generates a consecutive timeslot schedule along the packet forwarding path to minimize the packet transmission delay. The schedule is generated autonomously by utilizing only the local routing topology information without any additional signaling with other nodes. The generated schedule is guaranteed to be conflict-free, in that all nodes in the network could transmit packets to the sink in every slotframe cycle. We implement Escalator and evaluate its performance with existing autonomous scheduling schemes through a testbed and simulation. Experimental results show that the proposed Escalator has lower end-to-end delay and higher packet delivery ratio compared to the existing schemes regardless of the network topology. PMID:29659508

Escalation of drug self-administration as a hallmark of persistent addiction liability

PubMed Central

Edwards, Scott; Koob, George F.

2013-01-01

Drug addiction is a progressive, relapsing disease comprised of interlocking stages of disordered motivation. Numerous animal models describing various stages of the addiction process have been developed over the past few decades, providing considerable advantages for the modeling of drug addiction compared with other complex psychiatric disease states. Escalation of drug self-administration has emerged as a widely accepted operant conditioning model of excessive drug intake. We further argue here that drug-escalated animals represent a comprehensive model of addiction according to the manifestations of behavioral neuroadaptations resulting directly or indirectly from excessive drug consumption. In particular, drug-escalated animals exhibit a host of symptoms in line with multiple Diagnostic and Statistical Manual of Mental Disorders criteria for substance dependence, which can be summarized as an emergence of uncontrollable drug-taking and drug-seeking behaviors as a consequence of within-circuit and between-circuit neuroadaptations. Such a transition from impulsive drug sampling to compulsive intake represents a highly valid conceptualization of the addiction timeline in humans, and further investigation of persistent or near-permanent (e.g. epigenetic) neuroadaptations generated by operant drug intake escalation models will continue to provide mechanisms and therapeutic interventions for reversing the aberrant neuroplasticity underlying addiction. PMID:23839030

Dose escalation methods in phase I cancer clinical trials.

PubMed

Le Tourneau, Christophe; Lee, J Jack; Siu, Lillian L

2009-05-20

Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents. Toxicity has traditionally been the primary endpoint for phase I trials involving cytotoxic agents. However, with the emergence of molecularly targeted anticancer agents, potential alternative endpoints to delineate optimal biological activity, such as plasma drug concentration and target inhibition in tumor or surrogate tissues, have been proposed along with new trial designs. We also describe specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints. Finally, we present the advantages and drawbacks of the various dose escalation methods and discuss specific applications of the methods in developmental oncotherapeutics.

Tobacco use harm reduction, elimination, and escalation in a large military cohort.

PubMed

Klesges, Robert C; Sherrill-Mittleman, Deborah; Ebbert, Jon O; Talcott, G Wayne; Debon, Margaret

2010-12-01

We evaluated changing patterns of tobacco use following a period of forced tobacco abstinence in a US military cohort to determine rates of harm elimination (e.g., tobacco cessation), harm reduction (e.g., from smoking to smokeless tobacco use), and harm escalation (e.g., from smoking to dual use or from smokeless tobacco use to smoking or dual use). Participants were 5225 Air Force airmen assigned to the health education control condition in a smoking cessation and prevention trial. Tobacco use was assessed by self-report at baseline and 12 months. Among 114 baseline smokers initiating smokeless tobacco use after basic military training, most demonstrated harm escalation (87%), which was 5.4 times more likely to occur than was harm reduction (e.g., smoking to smokeless tobacco use). Harm reduction was predicted, in part, by higher family income and belief that switching from cigarettes to smokeless tobacco is beneficial to health. Harm escalation predictors included younger age, alcohol use, longer smoking history, and risk-taking. When considering a harm reduction strategy with smokeless tobacco, the tobacco control community should balance anticipated benefits of harm reduction with the risk of harm escalation and the potential for adversely affecting public health.

Escalator: An Autonomous Scheduling Scheme for Convergecast in TSCH.

PubMed

Oh, Sukho; Hwang, DongYeop; Kim, Ki-Hyung; Kim, Kangseok

2018-04-16

Time Slotted Channel Hopping (TSCH) is widely used in the industrial wireless sensor networks due to its high reliability and energy efficiency. Various timeslot and channel scheduling schemes have been proposed for achieving high reliability and energy efficiency for TSCH networks. Recently proposed autonomous scheduling schemes provide flexible timeslot scheduling based on the routing topology, but do not take into account the network traffic and packet forwarding delays. In this paper, we propose an autonomous scheduling scheme for convergecast in TSCH networks with RPL as a routing protocol, named Escalator. Escalator generates a consecutive timeslot schedule along the packet forwarding path to minimize the packet transmission delay. The schedule is generated autonomously by utilizing only the local routing topology information without any additional signaling with other nodes. The generated schedule is guaranteed to be conflict-free, in that all nodes in the network could transmit packets to the sink in every slotframe cycle. We implement Escalator and evaluate its performance with existing autonomous scheduling schemes through a testbed and simulation. Experimental results show that the proposed Escalator has lower end-to-end delay and higher packet delivery ratio compared to the existing schemes regardless of the network topology.

20. BANKING ROOM, LOOKING SOUTH FROM NORTHWEST CORNER, SHOWING ESCALATOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. BANKING ROOM, LOOKING SOUTH FROM NORTHWEST CORNER, SHOWING ESCALATOR ENTRANCE FROM STREET ON RIGHT AND BALCONY EDGES OF TWO MEZZANINES BEYOND - Philadelphia Saving Fund Society, Twelfth & Market Streets, Philadelphia, Philadelphia County, PA

Stimulus-dependent modulation of spontaneous low-frequency oscillations in the rat visual cortex.

PubMed

Huang, Liangming; Liu, Yadong; Gui, Jianjun; Li, Ming; Hu, Dewen

2014-08-06

Research on spontaneous low-frequency oscillations is important to reveal underlying regulatory mechanisms in the brain. The mechanism for the stimulus modulation of low-frequency oscillations is not known. Here, we used the intrinsic optical imaging technique to examine stimulus-modulated low-frequency oscillation signals in the rat visual cortex. The stimulation was presented monocularly as a flashing light with different frequencies and intensities. The phases of low-frequency oscillations in different regions tended to be synchronized and the rhythms typically accelerated within a 30-s period after stimulation. These phenomena were confined to visual stimuli with specific flashing frequencies (12.5-17.5 Hz) and intensities (5-10 mA). The acceleration and synchronization induced by the flashing frequency were more marked than those induced by the intensity. These results show that spontaneous low-frequency oscillations can be modulated by parameter-dependent flashing lights and indicate the potential utility of the visual stimulus paradigm in exploring the origin and function of low-frequency oscillations.

A phenomenological study of the long-term cosmic ray modulation, 850-1958 AD

NASA Astrophysics Data System (ADS)

McCracken, K. G.; McDonald, F. B.; Beer, J.; Raisbeck, G.; Yiou, F.

2004-12-01

The modulation of the galactic cosmic radiation over the past 1150 years is investigated using 10Be data from Greenland and the South Pole. For this purpose, we introduce the use of 22-year averages to study the long-term modulation. After allowance for secular changes in the geomagnetic dipole, it is shown that the 22-year mean intensity of the galactic cosmic radiation (GCR) in the vicinity of 1-2 GeV/nucleon returned to approximately the same high level at the widely separated times of the Oort (1050 AD), Spoerer (1420-1540), and the latter portion of the Maunder (1645-1715) periods of low solar activity. In terms of the modulation potential, ϕ, this asymptotic intensity corresponds to a mean residual modulation of ˜84 MV. The GCR intensity was significantly less during the Wolf (˜1320) and Dalton (1810) minima, and ϕ ˜ 200 MV. The higher temporal resolution data from Greenland shows that there were large 11-year and other fluctuations superimposed upon these high intensities during the Spoerer and Maunder minima (Δϕ ≈ 200-300 MV), indicating the continued presence of a substantial and time-dependent heliomagnetic field. Throughout the Spoerer minimum, the GCR intensity repeatedly returned to a condition of very low modulation, indicating that the cosmic ray spectrum incident on the Earth approached the level of the local interstellar spectrum. These results imply the continued presence of either (or both) (1) the normal cyclic variation of the heliospheric current sheet and/or (2) a cyclic variation of the diffusion coefficients throughout these periods of low solar activity. The data indicate that the modulation (i.e., depression) of the cosmic ray intensity during the instrumental era (1933-present) has been one of the greatest in the past 1150 years. Further, approximately the same low value has been attained on five previous widely separated occasions since 850 AD, and we speculate that the heliospheric magnetic field has reached an asymptotic limit at those times. The 10Be data exhibit a previously unrecognized feature, which we have named "the precipitous decrease," in which the 1-2 GeV/nucleon intensity decreased by ˜40-45% between 1700 and 1739 corresponding to Δϕ > 500 MV, at a time of low but increasing solar activity. A lower cosmic ray intensity than that attained in 1739 was not observed again until after 1950, at a time of high solar activity. These features and the large 11-year modulation events during the Spoerer and Maunder minima indicate that the long-term variations in the GCR intensity are poorly related to sunspot number during epochs of low solar activity. It is shown that there is better agreement between the variations in the 10Be data, and the changes in the open solar magnetic flux predicted by the [2002] and [2002] models based on historic sunspot numbers. In particular, they both exhibit characteristics consistent with the precipitous decrease in the 10Be data, although the amplitudes are smaller than implied by the 10Be data.

Cost-effective bidirectional digitized radio-over-fiber systems employing sigma delta modulation

NASA Astrophysics Data System (ADS)

Lee, Kyung Woon; Jung, HyunDo; Park, Jung Ho

2016-11-01

We propose a cost effective digitized radio-over-fiber (D-RoF) system employing a sigma delta modulation (SDM) and a bidirectional transmission technique using phase modulated downlink and intensity modulated uplink. SDM is transparent to different radio access technologies and modulation formats, and more suitable for a downlink of wireless system because a digital to analog converter (DAC) can be avoided at the base station (BS). Also, Central station and BS share the same light source by using a phase modulation for the downlink and an intensity modulation for the uplink transmission. Avoiding DACs and light sources have advantages in terms of cost reduction, power consumption, and compatibility with conventional wireless network structure. We have designed a cost effective bidirectional D-RoF system using a low pass SDM and measured the downlink and uplink transmission performance in terms of error vector magnitude, signal spectra, and constellations, which are based on the 10MHz LTE 64-QAM standard.

Optical gating with organic building blocks. A quantitative model for the fluorescence modulation of photochromic perylene bisimide dithienylcyclopentene triads

PubMed Central

Pärs, Martti; Gradmann, Michael; Gräf, Katja; Bauer, Peter; Thelakkat, Mukundan; Köhler, Jürgen

2014-01-01

We investigated the capability of molecular triads, consisting of two strong fluorophores that were covalently linked to a photochromic molecule, for optical gating. Therefore we monitored the fluorescence intensity of the fluorophores as a function of the isomeric state of the photoswitch. From the analysis of our data we develop a kinetic model that allows us to predict quantitatively the degree of the fluorescence modulation as a function of the mutual intensities of the lasers that are used to induce the fluorescence and the switching of the photochromic unit. We find that the achievable contrast for the modulation of the fluorescence depends mainly on the intensity ratio of the two light beams and appears to be very robust against absolute changes of these intensities. The latter result provides valuable information for the development of all-optical circuits which would require to handle different signal strengths for the input and output levels. PMID:24614963

The dependence of solar modulation on the sign of the cosmic ray particle charge

NASA Technical Reports Server (NTRS)

Garcia-Munoz, M.; Meyer, P.; Pyle, K. R.; Simpson, J. A.; Evenson, P. A.

1985-01-01

The solar modulation of galactic cosmic ray helium and electrons at 1 AU, within the 600-1000 MV magnetic rigidity interval, are compared for the period from 1965 through 1984. The time-intensity variations during the two solar maxima around 1970 and 1981 show that after 1970 the helium intensity recovers earlier than that of the electrons, whereas after 1981 the electron intensity recovers earlier than that of helium. The flux ratio of helium to electrons (He/e) undergoes a major increases during the 1969-1971 period and a major decrease during 1979-83. These experimental results can be interpreted as due to a dependence of the solar modulation of galactic cosmic rays on the sign of the particle charge, possibly as a consequence of drifts due to gradients and curvatures in the interplanetary magnetic field. However, the comparison of the shapes of the intensity-time curves of helium and electrons in the period 1970-1981 does not support a major specific prediction of the drift model.

Observational evidence that urbanisation and neighbourhood deprivation are associated with escalation in chronic pharmacological pain treatment: a longitudinal population-based study in the Netherlands

PubMed Central

Buijs, Servaas; Strik, Jacqueline; Lousberg, Richel; Smit, Jasper; van Kleef, Maarten; van Os, Jim

2012-01-01

Objective To examine, in the light of the association between urban environment and poor mental health, whether urbanisation and neighbourhood deprivation are associated with analgesic escalation in chronic pharmacological pain treatment and whether escalation is associated with prescriptions of psychotropic medication. Design Longitudinal analysis of a population-based routine dispensing database in the Netherlands. Setting Representative sample of pharmacies, covering 73% of the Dutch nationwide medication consumption in the primary care and hospital outpatient settings. Participants 449 410 patients aged 15–85 years were included, of whom 166 374 were in the Starter group and 283 036 in the Continuation group of chronic analgesic treatment. Main outcome measure Escalation of analgesics (ie, change to a higher level of analgesic potency, classified across five levels) in association with urbanisation (five levels) and dichotomous neighbourhood deprivation was analysed over a 6-month observation period. Methods Ordered logistic multivariate model evaluating analgesic treatment. Results In both Starter and Continuation groups, escalation was positively associated with urbanisation in a dose–response fashion (Starter group: OR (urbanisation level 1 compared with level 5): 1.24, 95% CI 1.18 to 1.30; Continuation group: OR 1.18, 95% CI 1.14 to 1.23). An additional association was apparent with neighbourhood deprivation (Starter group: OR 1.07, 95% CI 1.02 to 1.11; Continuation group: OR 1.04, 95% CI 1.01 to 1.08). Use of somatic and particularly psychotropic co-medication was associated with escalation in both groups. Conclusions Escalation of chronic analgesic treatment is associated with urban and deprived environments and occurs in a context of adding psychotropic medication prescriptions. These findings suggest that pain outcomes and mental health outcomes share factors that increase risk and remedy suffering. PMID:22815464

Dosimetric effect of beam arrangement for intensity-modulated radiation therapy in the treatment of upper thoracic esophageal carcinoma.

PubMed

Fu, Yuchuan; Deng, Min; Zhou, Xiaojuan; Lin, Qiang; Du, Bin; Tian, Xue; Xu, Yong; Wang, Jin; Lu, You; Gong, Youling

2017-01-01

To evaluate the lung sparing in intensity-modulated radiation therapy (IMRT) for patients with upper thoracic esophageal tumors extending inferiorly to the thorax by different beam arrangement. Overall, 15 patient cases with cancer of upper thoracic esophagus were selected for a retrospective treatment-planning study. Intensity-modulated radiation therapy plans using 4, 5, and 7 beams (4B, 5B, and 7B) were developed for each patient by direct machine parameter optimization (DMPO). All plans were evaluated with respect to dose volumes to irradiated targets and normal structures, with statistical comparisons made between 4B with 5B and 7B intensity-modulated radiation therapy plans. Differences among plans were evaluated using a two-tailed Friedman test at a statistical significance of p < 0.05. The maximum dose, average dose, and the conformity index (CI) of planning target volume 1 (PTV1) were similar for 3 plans for each case. No significant difference of coverage for planning target volume 1 and maximum dose for spinal cords were observed among 3 plans in present study (p > 0.05). The average V 5 , V 13 , V 20 , mean lung dose, and generalized equivalent uniform dose (gEUD) for the total lung were significantly lower in 4B-plans than those data in 5B-plans and 7B-plans (p < 0.01). Although the average V 30 for the total lung were significantly higher in 4B-plans than those in 5B-plans and 7B-plans (p < 0.05). In addition, when comparing with the 4B-plans, the conformity/heterogeneity index of the 5B- and 7B-plans were significantly superior (p < 0.05). The 4B-intensity-modulated radiation therapy plan has advantage to address the specialized problem of lung sparing to low- and intermediate-dose exposure in the thorax when dealing with relative long tumors extended inferiorly to the thoracic esophagus for upper esophageal carcinoma with the cost for less conformity. Studies are needed to compare the superiority of volumetric modulated arc therapy with intensity-modulated radiation therapy technique. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Numerical investigation of output beam quality in efficient broadband optical parametric chirped pulse amplification

NASA Astrophysics Data System (ADS)

Liu, Xiao-Di; Xu, Lu; Liang, Xiao-Yan

2017-01-01

We theoretically analyzed output beam quality of broad bandwidth non-collinear optical parametric chirped pulse amplification (NOPCPA) in LiB3O5 (LBO) centered at 800 nm. With a three-dimensional numerical model, the influence of the pump intensity, pump and signal spatial modulations, and the walk-off effect on the OPCPA output beam quality are presented, together with conversion efficiency and the gain spectrum. The pump modulation is a dominant factor that affects the output beam quality. Comparatively, the influence of signal modulation is insignificant. For a low-energy system with small beam sizes, walk-off effect has to be considered. Pump modulation and walk-off effect lead to asymmetric output beam profile with increased modulation. A special pump modulation type is found to optimize output beam quality and efficiency. For a high-energy system with large beam sizes, the walk-off effect can be neglected, certain back conversion is beneficial to reduce the output modulation. A trade-off must be made between the output beam quality and the conversion efficiency, especially when the pump modulation is large since. A relatively high conversion efficiency and a low output modulation are both achievable by controlling the pump modulation and intensity.

Attachment and Jealousy: Understanding the Dynamic Experience of Jealousy Using the Response Escalation Paradigm.

PubMed

Huelsnitz, Chloe O; Farrell, Allison K; Simpson, Jeffry A; Griskevicius, Vladas; Szepsenwol, Ohad

2018-04-01

Jealousy is a complex, dynamic experience that unfolds over time in relationship-threatening situations. Prior research has used retrospective reports that cannot disentangle initial levels and change in jealousy in response to escalating threat. In three studies, we examined responses to the Response Escalation Paradigm (REP)-a 5-stage hypothetical scenario in which individuals are exposed to increasing levels of relationship threat-as a function of attachment orientations. Highly anxious individuals exhibited hypervigilant, slow escalation response patterns, interfered earlier in the REP, felt more jealousy, sadness, and worry when they interfered, and wanted to engage in more vigilant, destructive, and passive behaviors aimed at their partner. Highly avoidant individuals felt more anger when they interfered in the REP and wanted to engage in more partner-focused, destructive behaviors. The REP offers a dynamic method for inducing and examining jealousy and introduces a novel approach to studying other emotional experiences.

Maternal depression and trait anger as risk factors for escalated physical discipline.

PubMed

Shay, Nicole L; Knutson, John F

2008-02-01

To test the hypothesized anger-mediated relation between maternal depression and escalation of physical discipline, 122 economically disadvantaged mothers were assessed for current and lifetime diagnoses of depression using the Current Depressive Episode, Past Depression, and Dysthymia sections of the Structured Clinical Interview for DSM-IV (SCID) and a measure of current depressive symptoms, the Beck Depression Inventory-Second Edition (BDI-II). Escalation of physical discipline was assessed using a video analog parenting task; maternal anger not specific to discipline was assessed using the Spielberger Trait Anger Expression Inventory. Reports of anger were associated with the diagnosis of depression and depressive symptoms. Bootstrap analyses of indirect effects indicated that the link between depression and escalated discipline was mediated by anger. Parallel analyses based on BDI-II scores identified a marginally significant indirect effect of depression on discipline. Findings suggest that anger and irritability are central to the putative link between depression and harsh discipline.

Promoting de-escalation of commitment: a regulatory-focus perspective on sunk costs.

PubMed

Molden, Daniel C; Hui, Chin Ming

2011-01-01

People frequently escalate their commitment to failing endeavors. Explanations for such behavior typically involve loss aversion, failure to recognize other alternatives, and concerns with justifying prior actions; all of these factors produce recommitment to previous decisions with the goal of erasing losses and vindicating these decisions. Solutions to escalation of commitment have therefore focused on external oversight and divided responsibility during decision making to attenuate loss aversion, blindness to alternatives, and justification biases. However, these solutions require substantial resources and have additional adverse effects. The present studies tested an alternative method for de-escalating commitment: activating broad motivations for growth and advancement (promotion). This approach should reduce concerns with loss and increase perceptions of alternatives, thereby attenuating justification motives. In two studies featuring hypothetical financial decisions, activating promotion motivations reduced recommitment to poorly performing investments as compared with both not activating any additional motivations and activating motivations for safety and security (prevention).

Evolutionary aspects of anxiety disorders.

PubMed

Price, John S

2003-09-01

DANGER AND HARM ARE AVOIDED BY STRATEGIC DECISIONS MADE AT ALL THREE LEVELS OF THE TRIUNE FOREBRAIN: rational (neomammalian), emotional (paleomammalian), and instinctive (reptilian). This applies also to potential harm from conspecifics, which leads to a choice between escalating and de-escalating strategies. Anxiety is a component of de-escalating strategies mediated by the paleomammalian and reptilian forebrains. When the neomammalian (rational) brain fails to deal with the threat of conspecific danger, these more primitive de-escalating strategies may be activated and may present as anxiety disorders. The capacity for concealment of anxiety and other forms of negative affect has also evolved, and excessive concealment may lead to psychopaihology by breaking the negative feedback loop of excessive motivation, leading to impaired performance, leading to signals of distress, and leading to reduced exhortation to succeed on the part of parents and teachers; this situation is illustrated by a model based on the Yerkes-Dodson law.

Evolutionary aspects of anxiety disorders

PubMed Central

Price, John S.

2003-01-01

Danger and harm are avoided by strategic decisions made at all three levels of the triune forebrain: rational (neomammalian), emotional (paleomammalian), and instinctive (reptilian). This applies also to potential harm from conspecifics, which leads to a choice between escalating and de-escalating strategies. Anxiety is a component of de-escalating strategies mediated by the paleomammalian and reptilian forebrains. When the neomammalian (rational) brain fails to deal with the threat of conspecific danger, these more primitive de-escalating strategies may be activated and may present as anxiety disorders. The capacity for concealment of anxiety and other forms of negative affect has also evolved, and excessive concealment may lead to psychopaihology by breaking the negative feedback loop of excessive motivation, leading to impaired performance, leading to signals of distress, and leading to reduced exhortation to succeed on the part of parents and teachers; this situation is illustrated by a model based on the Yerkes-Dodson law. PMID:22033473

Cosmic Ray Hysteresis as Evidence for Time-dependent Diffusive Processes in the Long Term Solar Modulation

NASA Technical Reports Server (NTRS)

Ogallagher, J. J.

1973-01-01

A simple one-dimensional time-dependent diffusion-convection model for the modulation of cosmic rays is presented. This model predicts that the observed intensity at a given time is approximately equal to the intensity given by the time independent diffusion convection solution under interplanetary conditions which existed a time iota in the past, (U(t sub o) = U sub s(t sub o - tau)) where iota is the average time spent by a particle inside the modulating cavity. Delay times in excess of several hundred days are possible with reasonable modulation parameters. Interpretation of phase lags observed during the 1969 to 1970 solar maximum in terms of this model suggests that the modulating region is probably not less than 10 a.u. and maybe as much as 35 a.u. in extent.

Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollom, Erqi L.; Fujimoto, Dylann; Wynne, Jacob

Purpose: We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide. Methods: HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory–Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (globalmore » quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point. Results: With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01). Conclusion: On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.« less

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner.

PubMed

Cannady, Reginald; Fisher, Kristen R; Graham, Caitlin; Crayle, Jesse; Besheer, Joyce; Hodge, Clyde W

2017-05-01

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here, we show that low-dose alcohol (0.6 g/kg/30 minutes) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared with behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol-reinforced but not sucrose-reinforced responding and was ineffective following intra-AcbC infusion. Because GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor myristolated autocamtide-2-related inhibitory peptide (m-AIP) dose-dependently reduced alcohol self-administration. A subthreshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use via increased positive reinforcement during the initial stages of addiction. © 2016 Society for the Study of Addiction.

Intensity-Modulated Advanced X-ray Source (IMAXS) for Homeland Security Applications

NASA Astrophysics Data System (ADS)

Langeveld, Willem G. J.; Johnson, William A.; Owen, Roger D.; Schonberg, Russell G.

2009-03-01

X-ray cargo inspection systems for the detection and verification of threats and contraband require high x-ray energy and high x-ray intensity to penetrate dense cargo. On the other hand, low intensity is desirable to minimize the radiation footprint. A collaboration between HESCO/PTSE Inc., Schonberg Research Corporation and Rapiscan Laboratories, Inc. has been formed in order to design and build an Intensity-Modulated Advanced X-ray Source (IMAXS). Such a source would allow cargo inspection systems to achieve up to two inches greater imaging penetration capability, while retaining the same average radiation footprint as present fixed-intensity sources. Alternatively, the same penetration capability can be obtained as with conventional sources with a reduction of the average radiation footprint by about a factor of three. The key idea is to change the intensity of the source for each x-ray pulse based on the signal strengths in the inspection system detector array during the previous pulse. In this paper we describe methods to accomplish pulse-to-pulse intensity modulation in both S-band (2998 MHz) and X-band (9303 MHz) linac sources, with diode or triode (gridded) electron guns. The feasibility of these methods has been demonstrated. Additionally, we describe a study of a shielding design that would allow a 6 MV X-band source to be used in mobile applications.

Application of ultrasound-tagged photons for measurement of amplitude of vibration of tissue caused by ultrasound: theory, simulation, and experiments.

PubMed

Devi, C Usha; Vasu, R M; Sood, A K

2006-01-01

We investigate the modulation of an optical field caused by its interaction with an ultrasound beam in a tissue mimicking phantom. This modulation appears as a modulation in the intensity autocorrelation, which is measured by a photon counting correlator. The factors contributing to the modulation are: 1. amplitude of vibration of the particles of the tissue, 2. refractive index modulation, and 3. absorption coefficient in the region of the tissue intercepted by the ultrasound beam and light. We show in this work that a significant part of the contribution to this modulation comes from displacement of the tissue particles, which in turn is governed by the elastic properties of the tissue. We establish, both through simulations and experiments using an optical elastography phantom, the effects of the elasticity and absorption coefficient variations on the modulation of intensity autocorrelation. In the case where there is no absorption coefficient variation, we suggest that the depth of modulation can be calibrated to measure the displacement of tissue particles that, in turn, can be used to measure the tissue elasticity.

Preventing and De-escalating Aggressive Behavior Among Adult Psychiatric Patients: A Systematic Review of the Evidence.

PubMed

Gaynes, Bradley N; Brown, Carrie L; Lux, Linda J; Brownley, Kimberly A; Van Dorn, Richard A; Edlund, Mark J; Coker-Schwimmer, Emmanuel; Weber, Rachel Palmieri; Sheitman, Brian; Zarzar, Theodore; Viswanathan, Meera; Lohr, Kathleen N

2017-08-01

The project goal was to compare the effectiveness of strategies to prevent and de-escalate aggressive behaviors among psychiatric patients in acute care settings, including interventions for reducing use of seclusion and restraint. Relevant databases were systematically reviewed for comparative studies of violence prevention and de-escalation strategies involving adult psychiatric patients in acute care settings. Studies (trials and cohort studies) were required to report on aggression or seclusion or restraint outcomes. Both risk of bias, an indicator of quality of individual studies, and strength of evidence (SOE) for each outcome were independently assessed by two study personnel. Seventeen primary studies met inclusion criteria. Evidence was limited for benefits and harms; information about characteristics that might modify the interventions' effectiveness, such as race or ethnicity, was especially limited. All but one study had a medium or high risk of bias and thus presented worrisome limitations. For prevention, risk assessment reduced both aggression and use of seclusion and restraint (low SOE), and multimodal interventions reduced the use of seclusion and restraint (low SOE). SOE for all other interventions, whether aimed at preventing or de-escalating aggression, and for modifying characteristics was insufficient. Available evidence about strategies for preventing and de-escalating aggressive behavior among psychiatric patients is very limited. Two preventive strategies, risk assessment and multimodal interventions consistent with the Six Core Strategies principles, may effectively lower aggressive behavior and use of seclusion and restraint, but more research is needed on how best to prevent and de-escalate aggressive behavior in acute care settings.

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

PubMed

Hudson, Andrew; Chan, Clara; Woolf, David; McWilliam, Alan; Hiley, Crispin; O'Connor, James; Bayman, Neil; Blackhall, Fiona; Faivre-Finn, Corinne

2018-04-01

The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected. Copyright © 2018 Elsevier B.V. All rights reserved.

Behavioral characterization of escalated aggression induced by GABAB receptor activation in the dorsal raphé nucleus

PubMed Central

Takahashi, Aki; Schilit, Arielle N.; Kim, Jisoo; DeBold, Joseph F.; Koide, Tsuyoshi; Miczek, Klaus A.

2013-01-01

Rationale Pharmacological activation of GABAB receptors in the dorsal raphé nucleus (DRN) can escalate territorial aggression in male mice. Objectives We characterized this escalated aggression in terms of its behavioral and environmental determinants. Methods Aggressive behavior of resident male (CFW or ICR mouse) was assessed in confrontations with a group-housed intruder. Either baclofen (0.06 nmol/0.2 μl) or vehicle (saline) was microinjected into the DRN ten minutes before the confrontation. We examined baclofen-heightened aggression in five situations: aggression in a neutral arena and after social instigation (experiment 1), aggression during the light phase of the cycle (experiment 2), aggression without prior fighting experience (experiment 3), aggression toward a female (experiment 4), and aggression after defeat experiences (experiment 5). In addition, we examined the body targets towards which bites are directed and the duration of aggressive bursts after baclofen treatment. Results Regardless of the past social experience, baclofen escalated aggressive behaviors. Even in the neutral arena and after defeat experiences, where aggressive behaviors were inhibited, baclofen significantly increased aggression. Baclofen increased attack bites directed at vulnerable body areas of male intruders but not toward a female and only in the dark. Also, baclofen prolonged the duration of aggressive bursts. Conclusions For baclofen to escalate aggression, specific stimulation (male intruder) and tonic level of serotonin (dark cycle) are required. Once aggressive behavior is triggered, intra-DRN baclofen escalates the level of aggression to abnormal levels and renders it difficult to terminate. Also, baclofen counteracts the effects of novelty or past experiences of defeat. PMID:22395428

Suicide Attempts in a Longitudinal Sample of Adolescents Followed Through Adulthood: Evidence of Escalation

PubMed Central

Goldston, David B.; Daniel, Stephanie S.; Erkanli, Alaattin; Heilbron, Nicole; Doyle, Otima; Weller, Bridget; Sapyta, Jeffrey

2015-01-01

Objectives This study was designed to examine escalation in repeat suicide attempts from adolescence through adulthood, as predicted by sensitization models (and reflected in increasing intent and lethality with repeat attempts, decreasing amount of time between attempts, and decreasing stress to trigger attempts) Method In a prospective study of 180 adolescents followed through adulthood after a psychiatric hospitalization, suicide attempts and antecedent life events were repeatedly assessed (M = 12.6 assessments, SD = 5.1) over an average of 13 years, 6 months (SD = 4 years, 5 months). Multivariate logistic, multiple linear, and negative binomial regression models were used to examine patterns over time. Results After age 17-18, the majority of suicide attempts were repeat attempts (i.e., made by individuals with prior suicidal behavior). Intent increased both with increasing age, and with number of prior attempts. Medical lethality increased as a function of age but not recurrent attempts. The time between successive suicide attempts decreased as a function of number of attempts. The amount of precipitating life stress was not related to attempts. Conclusions Adolescents and young adults show evidence of escalation of recurrent suicidal behavior, with increasing suicidal intent and decreasing time between successive attempts. However, evidence that sensitization processes account for this escalation was inconclusive. Effective prevention programs that reduce the likelihood of individuals attempting suicide for the first time (and entering this cycle of escalation), and relapse prevention interventions that interrupt the cycle of escalating suicidal behavior among individuals who already have made attempts are critically needed. PMID:25622200

Frequency analysis for modulation-enhanced powder diffraction.

PubMed

Chernyshov, Dmitry; Dyadkin, Vadim; van Beek, Wouter; Urakawa, Atsushi

2016-07-01

Periodic modulation of external conditions on a crystalline sample with a consequent analysis of periodic diffraction response has been recently proposed as a tool to enhance experimental sensitivity for minor structural changes. Here the intensity distributions for both a linear and nonlinear structural response induced by a symmetric and periodic stimulus are analysed. The analysis is further extended for powder diffraction when an external perturbation changes not only the intensity of Bragg lines but also their positions. The derived results should serve as a basis for a quantitative modelling of modulation-enhanced diffraction data measured in real conditions.

Monaco and film dosimetry of 3D CRT, IMRT and VMAT cases in a realistic pelvic prosthetic phantom

NASA Astrophysics Data System (ADS)

Ade, Nicholas; du Plessis, F. C. P.

2018-04-01

The dosimetry of patients with metallic hip implants during irradiation of pelvic lesions is challenging due to dose distortions caused by implants. This work presents a dosimetric comparison of various multi-field photon-beam dose distributions in the presence of unilateral hip titanium prosthesis (UHTiP) embedded in a unique pelvic phantom made out of water-equivalent nylon slices. The impact of the UHTiP on the accuracy of dose calculations from a Monaco TPS (treatment planning system) using the X-ray voxel Monte Carlo (XVMC) algorithm was benchmarked against measured dose data using Gafchromic EBT3 film. Multi-field beam arrangements including a 4-field box, 5-field 3DCRT (three-dimensional conformal radiation therapy), 6-field IMRT (intensity modulated radiation therapy) and a single-arc VMAT (volumetric modulated arc therapy) plan were set up for 6 MV and 15 MV beams. These plans were generated for the pelvic phantom that contains the prosthesis with film inserted. Compared to Monaco TPS dose calculations, film measurements showed enhanced dose in the prosthesis which was not predicted by Monaco due to its limitation in relative density assignment. The enhanced prosthesis dose increased with increase in beam energy and decreased with the complexity of the treatment plans, with VMAT giving the least escalated dose. The dose increased between 5% and 19% for 6 MV and between 6% and 21% for 15 MV. A gamma index analysis showed that 70-92% of dose points (excluding the prosthesis) were within 3% discrepancy. Increasing the number of treatment fields increases target dose coverage and improves the agreement between film and Monaco. When the relative electron density (RED) in the prosthesis was varied between 3.72 and 15 the dose discrepancy between film and Monaco increased from 30% to 57% for 6 MV and from 30% to 50% for 15 MV. The study indicates that beam weights for fields that pass through the prosthesis should be minimised and its RED must be correct for accurate dose calculation on Monaco.

Organizational Conflict Management as Disputing Process: The Problem of Social Escalation.

ERIC Educational Resources Information Center

Morrill, Calvin; Thomas, Cheryl King

1992-01-01

Develops an instrument to study organizational conflict management as a disputing process involving the social escalation from grievance to conflict and dispute stages. Finds differences in dispute process according to different strengths of informal relations. (SR)

School District Health Care Expense: Moderating the Escalation Rate.

ERIC Educational Resources Information Center

Abel, Gene P.

1991-01-01

The cafeteria plan for health insurance benefits employers by reducing the overall escalation of health costs. Employees benefit by tailoring their benefit packages to their needs to including the option to decline coverage because of spouse employment. (MLF)

Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

ClinicalTrials.gov

2018-02-13

Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

The Conception Approach to the Traffic Control in Czech Cities - Examples from Prague

NASA Astrophysics Data System (ADS)

Tichý, Tomáš; Krajčír, Dušan

Modern and economic development of contemporary towns is without question highly dependent upon traffic infrastructure progress. Automobile transport intensity is dramatically rising in large towns and other Czech and European cities. At the same time number of traffic congestions and accidents is increasing, standing times are becoming longer and ecological stress is also escalated. To solve this situation seems to be the most effective solution to design intelligent traffic light intersection control system, variable message signs, preference of public transportation, road line traffic control and next telematics subsystems. This control system and subsystems should improve permeability of traffic road network with a respect for all demands on recent trends of traffic development in towns and regions.

Optically-gated Non-latched High Gain Power Device

DTIC Science & Technology

2008-11-21

parameters such as power conversion efficiency, dv/dt and di/dt stress on PSD and electromagnetic noise emission spectrum, which depend directly on the...4. EXPERIMENTAL STUDIES ON OTPT AND OPTICAL INTENSITY MODULATION OF OTPT PARAMETERS 33 4.1 Optical source, driver, and fiber details 33 4.2...off dynamics characterizations 36 4.5. Optical intensity modulation of OTPT parameters 37 5. EXPERIMENTAL STUDIES ON HYBRID OTPT-PSD AND OPTICAL

A molecular-sized optical logic circuit for digital modulation of a fluorescence signal

NASA Astrophysics Data System (ADS)

Nishimura, Takahiro; Tsuchida, Karin; Ogura, Yusuke; Tanida, Jun

2018-03-01

Fluorescence measurement allows simultaneous detection of multiple molecular species by using spectrally distinct fluorescence probes. However, due to the broad spectra of fluorescence emission, the multiplicity of fluorescence measurement is generally limited. To overcome this limitation, we propose a method to digitally modulate fluorescence output signals with a molecular-sized optical logic circuit by using optical control of fluorescence resonance energy transfer (FRET). The circuit receives a set of optical inputs represented with different light wavelengths, and then it switches high and low fluorescence intensity from a reporting molecule according to the result of the logic operation. By using combinational optical inputs in readout of fluorescence signals, the number of biomolecular species that can be identified is increased. To implement the FRET-based circuits, we designed two types of basic elements, YES and NOT switches. An YES switch produces a high-level output intensity when receiving a designated light wavelength input and a low-level intensity without the light irradiation. A NOT switch operates inversely to the YES switch. In experiments, we investigated the operation of the YES and NOT switches that receive a 532-nm light input and modulate the fluorescence intensity of Alexa Fluor 488. The experimental result demonstrates that the switches can modulate fluorescence signals according to the optical input.

Power requirements reducing of FBG based all-optical switching

NASA Astrophysics Data System (ADS)

Scholtz, Ľubomír.; Solanská, Michaela; Ladányi, Libor; Müllerová, Jarmila

2017-12-01

Although Fiber Bragg gratings (FBGs) are well known devices, their using as all-optical switching elements has been still examined. Current research is focused on optimization of their properties for their using in future all-optical networks. The main problem are high switching intensities needed for achieving the changes of the transmission state. Over several years switching intensities have been reduced from hundreds of GW/cm2 to tens of MW/cm2 by selecting appropriate gratings and signal parameters or using suitable materials. Two principal nonlinear effects with similar power requirements can result in the bistable transmission/reflection of an input optical pulse. In the self-phase modulation (SPM) regime switching is achieved by the intense probe pulse itself. Using cross-phase modulation (XPM) a strong pump alters the FBG refractive index experienced by a weak probe pulse. As a result of this the detuning of the probe pulse from the center of the photonic band gap occurs. Using of XPM the effect of modulation instability is reduced. Modulation instability which is the main SPM degradation mechanism. We focused on nonlinear FBGs based on chalcogenide glasses which are very often used in various applications. Thanks to high nonlinear parameters chalcogenide glasses are suitable candidates for reducing switching intensities of nonlinear FBGs.

FusionArc optimization: a hybrid volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) planning strategy.

PubMed

Matuszak, Martha M; Steers, Jennifer M; Long, Troy; McShan, Daniel L; Fraass, Benedick A; Romeijn, H Edwin; Ten Haken, Randall K

2013-07-01

To introduce a hybrid volumetric modulated arc therapy/intensity modulated radiation therapy (VMAT/IMRT) optimization strategy called FusionArc that combines the delivery efficiency of single-arc VMAT with the potentially desirable intensity modulation possible with IMRT. A beamlet-based inverse planning system was enhanced to combine the advantages of VMAT and IMRT into one comprehensive technique. In the hybrid strategy, baseline single-arc VMAT plans are optimized and then the current cost function gradients with respect to the beamlets are used to define a metric for predicting which beam angles would benefit from further intensity modulation. Beams with the highest metric values (called the gradient factor) are converted from VMAT apertures to IMRT fluence, and the optimization proceeds with the mixed variable set until convergence or until additional beams are selected for conversion. One phantom and two clinical cases were used to validate the gradient factor and characterize the FusionArc strategy. Comparisons were made between standard IMRT, single-arc VMAT, and FusionArc plans with one to five IMRT∕hybrid beams. The gradient factor was found to be highly predictive of the VMAT angles that would benefit plan quality the most from beam modulation. Over the three cases studied, a FusionArc plan with three converted beams achieved superior dosimetric quality with reductions in final cost ranging from 26.4% to 48.1% compared to single-arc VMAT. Additionally, the three beam FusionArc plans required 22.4%-43.7% fewer MU∕Gy than a seven beam IMRT plan. While the FusionArc plans with five converted beams offer larger reductions in final cost--32.9%-55.2% compared to single-arc VMAT--the decrease in MU∕Gy compared to IMRT was noticeably smaller at 12.2%-18.5%, when compared to IMRT. A hybrid VMAT∕IMRT strategy was implemented to find a high quality compromise between gantry-angle and intensity-based degrees of freedom. This optimization method will allow patients to be simultaneously planned for dosimetric quality and delivery efficiency without switching between delivery techniques. Example phantom and clinical cases suggest that the conversion of only three VMAT segments to modulated beams may result in a good combination of quality and efficiency.

Use of PET and Other Functional Imaging to Guide Target Delineation in Radiation Oncology.

PubMed

Verma, Vivek; Choi, J Isabelle; Sawant, Amit; Gullapalli, Rao P; Chen, Wengen; Alavi, Abass; Simone, Charles B

2018-06-01

Molecular and functional imaging is increasingly being used to guide radiotherapy (RT) management and target delineation. This review summarizes existing data in several disease sites of various functional imaging modalities, chiefly positron emission tomography/computed tomography (PET/CT), with respect to RT target definition and management. For gliomas, differentiation between postoperative changes and viable tumor is discussed, as well as focal dose escalation and reirradiation. Head and neck neoplasms may also benefit from precise PET/CT-based target delineation, especially for cancers of unknown primary; focal dose escalation is also described. In lung cancer, PET/CT can influence coverage of tumor volumes, dose escalation, and adaptive management. For cervical cancer, PET/CT as an adjunct to magnetic resonance imaging planning is discussed, as are dose escalation and delineation of avoidance targets such as the bone marrow. The emerging role of choline-based PET for prostate cancer and its impact on dose escalation is also described. Lastly, given the essential role of PET/CT for target definition in lymphoma, phase III trials of PET-directed management are reviewed, along with novel imaging modalities. Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic care going forward. Copyright © 2018 Elsevier Inc. All rights reserved.

Rate adaptive multilevel coded modulation with high coding gain in intensity modulation direct detection optical communication

NASA Astrophysics Data System (ADS)

Xiao, Fei; Liu, Bo; Zhang, Lijia; Xin, Xiangjun; Zhang, Qi; Tian, Qinghua; Tian, Feng; Wang, Yongjun; Rao, Lan; Ullah, Rahat; Zhao, Feng; Li, Deng'ao

2018-02-01

A rate-adaptive multilevel coded modulation (RA-MLC) scheme based on fixed code length and a corresponding decoding scheme is proposed. RA-MLC scheme combines the multilevel coded and modulation technology with the binary linear block code at the transmitter. Bits division, coding, optional interleaving, and modulation are carried out by the preset rule, then transmitted through standard single mode fiber span equal to 100 km. The receiver improves the accuracy of decoding by means of soft information passing through different layers, which enhances the performance. Simulations are carried out in an intensity modulation-direct detection optical communication system using MATLAB®. Results show that the RA-MLC scheme can achieve bit error rate of 1E-5 when optical signal-to-noise ratio is 20.7 dB. It also reduced the number of decoders by 72% and realized 22 rate adaptation without significantly increasing the computing time. The coding gain is increased by 7.3 dB at BER=1E-3.

FM-to-AM modulations induced by a weak residual reflection stack of sine-modulated pulses in inertial confinement fusion laser systems

NASA Astrophysics Data System (ADS)

Huang, Xiaoxia; Deng, Xuewei; Zhou, Wei; Hu, Dongxia; Guo, Huaiwen; Wang, Yuancheng; Zhao, Bowang; Zhong, Wei; Deng, Wu

2018-02-01

We report on frequency to amplitude modulation (FM-to-AM) conversion induced by a weak residual reflection stack of sine-modulated pulses in a complex laser system. Theoretical and experimental investigations reveal that when weak residual reflected pulses stack on the main pulse, the spectral intensity changes in the stacked region, which then converts to obvious AM. This kind of FM-to-AM effect often occurs in the tail of the pulse and cannot be eliminated by common compensation methods, which even enhance the modulation depth. Furthermore, the actual intensity modulation frequency and depth induced by the residual reflection stack are much higher and deeper than observed on the oscilloscope, which is harmful for safe operation of the laser facility and the driving power balance during inertial confinement fusion. To eliminate this kind of FM-to-AM effect, any possible on-axis and near-axis residual reflection in laser systems must be avoided.

[Radiotherapy volume delineation based on (18F)-fluorodeoxyglucose positron emission tomography for locally advanced or inoperable oesophageal cancer].

PubMed

Encaoua, J; Abgral, R; Leleu, C; El Kabbaj, O; Caradec, P; Bourhis, D; Pradier, O; Schick, U

2017-06-01

To study the impact on radiotherapy planning of an automatically segmented target volume delineation based on ( 18 F)-fluorodeoxy-D-glucose (FDG)-hybrid positron emission tomography-computed tomography (PET-CT) compared to a manually delineation based on computed tomography (CT) in oesophageal carcinoma patients. Fifty-eight patients diagnosed with oesophageal cancer between September 2009 and November 2014 were included. The majority had squamous cell carcinoma (84.5 %), and advanced stage (37.9 % were stade IIIA) and 44.8 % had middle oesophageal lesion. Gross tumour volumes were retrospectively defined based either manually on CT or automatically on coregistered PET/CT images using three different threshold methods: standard-uptake value (SUV) of 2.5, 40 % of maximum intensity and signal-to-background ratio. Target volumes were compared in length, volume and using the index of conformality. Radiotherapy plans to the dose of 50Gy and 66Gy using intensity-modulated radiotherapy were generated and compared for both data sets. Planification target volume coverage and doses delivered to organs at risk (heart, lung and spinal cord) were compared. The gross tumour volume based manually on CT was significantly longer than that automatically based on signal-to-background ratio (6.4cm versus 5.3cm; P<0.008). Doses to the lungs (V20, D mean ), heart (V40), and spinal cord (D max ) were significantly lower on plans using the PTV SBR . The PTV SBR coverage was statistically better than the PTV CT coverage on both plans. (50Gy: P<0.0004 and 66Gy: P<0.0006). The automatic PET segmentation algorithm based on the signal-to-background ratio method for the delineation of oesophageal tumours is interesting, and results in better target volume coverage and decreased dose to organs at risk. This may allow dose escalation up to 66Gy to the gross tumour volume. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Influence of Smoking Consumption and Nicotine Dependence Degree in Cardiac Autonomic Modulation

PubMed Central

dos Santos, Ana Paula Soares; Ramos, Dionei; de Oliveira, Gabriela Martins; dos Santos, Ana Alice Soares; Freire, Ana Paula Coelho Figueira; It, Juliana Tiyaki; Fernandes, Renato Peretti Prieto; Vanderlei, Luiz Carlos Marques; Ramos, Ercy Mara Cipulo

2016-01-01

Background Smoking consumption alters cardiac autonomic function. Objective Assess the influence of the intensity of smoking and the nicotine dependence degree in cardiac autonomic modulation evaluated through index of heart rate variability (HRV). Methods 83 smokers, of both genders, between 50 and 70 years of age and with normal lung function were divided according to the intensity of smoking consumption (moderate and severe) and the nicotine dependency degree (mild, moderate and severe). The indexes of HRV were analyzed in rest condition, in linear methods in the time domain (TD), the frequency domain (FD) and through the Poincaré plot. For the comparison of smoking consumption, unpaired t test or Mann-Whitney was employed. For the analysis between the nicotine dependency degrees, we used the One-way ANOVA test, followed by Tukey's post test or Kruskal-Wallis followed by Dunn's test. The significance level was p < 0,05. Results Differences were only found when compared to the different intensities of smoking consumption in the indexes in the FD. LFun (62.89 ± 15.24 vs 75.45 ± 10.28), which corresponds to low frequency spectrum component in normalized units; HFun (37.11 ± 15.24 vs 24.55 ± 10.28), which corresponds to high frequency spectrum component in normalized units and in the LF/HF ratio (2.21 ± 1.47 vs 4.07 ± 2.94). However, in the evaluation of nicotine dependency, significant differences were not observed (p > 0.05). Conclusion Only the intensity of smoking consumption had an influence over the cardiac autonomic modulation of the assessed tobacco smokers. Tobacco smokers with severe intensity of smoking consumption presented a lower autonomic modulation than those with moderate intensity. PMID:27142649

THE EFFECT OF A DYNAMIC INNER HELIOSHEATH THICKNESS ON COSMIC-RAY MODULATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manuel, R.; Ferreira, S. E. S.; Potgieter, M. S., E-mail: rexmanuel@live.com

2015-02-01

The time-dependent modulation of galactic cosmic rays in the heliosphere is studied over different polarity cycles by computing 2.5 GV proton intensities using a two-dimensional, time-dependent modulation model. By incorporating recent theoretical advances in the relevant transport parameters in the model, we showed in previous work that this approach gave realistic computed intensities over a solar cycle. New in this work is that a time dependence of the solar wind termination shock (TS) position is implemented in our model to study the effect of a dynamic inner heliosheath thickness (the region between the TS and heliopause) on the solar modulationmore » of galactic cosmic rays. The study reveals that changes in the inner heliosheath thickness, arising from a time-dependent shock position, does affect cosmic-ray intensities everywhere in the heliosphere over a solar cycle, with the smallest effect in the innermost heliosphere. A time-dependent TS position causes a phase difference between the solar activity periods and the corresponding intensity periods. The maximum intensities in response to a solar minimum activity period are found to be dependent on the time-dependent TS profile. It is found that changing the width of the inner heliosheath with time over a solar cycle can shift the time of when the maximum or minimum cosmic-ray intensities occur at various distances throughout the heliosphere, but more significantly in the outer heliosphere. The time-dependent extent of the inner heliosheath, as affected by solar activity conditions, is thus an additional time-dependent factor to be considered in the long-term modulation of cosmic rays.« less

Rapamycin Pharmacokinetic and Pharmacodynamic Relationships in Osteosarcoma: A Comparative Oncology Study in Dogs

PubMed Central

Paoloni, Melissa C.; Mazcko, Christina; Fox, Elizabeth; Fan, Timothy; Lana, Susan; Kisseberth, William; Vail, David M.; Nuckolls, Kaylee; Osborne, Tanasa; Yalkowsy, Samuel; Gustafson, Daniel; Yu, Yunkai; Cao, Liang; Khanna, Chand

2010-01-01

Background Signaling through the mTOR pathway contributes to growth, progression and chemoresistance of several cancers. Accordingly, inhibitors have been developed as potentially valuable therapeutics. Their optimal development requires consideration of dose, regimen, biomarkers and a rationale for their use in combination with other agents. Using the infrastructure of the Comparative Oncology Trials Consortium many of these complex questions were asked within a relevant population of dogs with osteosarcoma to inform the development of mTOR inhibitors for future use in pediatric osteosarcoma patients. Methodology/Principal Findings This prospective dose escalation study of a parenteral formulation of rapamycin sought to define a safe, pharmacokinetically relevant, and pharmacodynamically active dose of rapamycin in dogs with appendicular osteosarcoma. Dogs entered into dose cohorts consisting of 3 dogs/cohort. Dogs underwent a pre-treatment tumor biopsy and collection of baseline PBMC. Dogs received a single intramuscular dose of rapamycin and underwent 48-hour whole blood pharmacokinetic sampling. Additionally, daily intramuscular doses of rapamycin were administered for 7 days with blood rapamycin trough levels collected on Day 8, 9 and 15. At Day 8 post-treatment collection of tumor and PBMC were obtained. No maximally tolerated dose of rapamycin was attained through escalation to the maximal planned dose of 0.08 mg/kg (2.5 mg/30kg dog). Pharmacokinetic analysis revealed a dose-dependent exposure. In all cohorts modulation of the mTOR pathway in tumor and PBMC (pS6RP/S6RP) was demonstrated. No change in pAKT/AKT was seen in tumor samples following rapamycin therapy. Conclusions/Significance Rapamycin may be safely administered to dogs and can yield therapeutic exposures. Modulation pS6RP/S6RP in tumor tissue and PBMCs was not dependent on dose. Results from this study confirm that the dog may be included in the translational development of rapamycin and potentially other mTOR inhibitors. Ongoing studies of rapamycin in dogs will define optimal schedules for their use in cancer and evaluate the role of rapamycin use in the setting of minimal residual disease. PMID:20543980

Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, Daniel, E-mail: dkrauss@beaumont.edu; Kestin, Larry; Ye, Hong

2011-07-15

Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presencemore » of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.« less

Vital signs and other observations used to detect deterioration in pregnant women: an analysis of vital sign charts in consultant-led UK maternity units.

PubMed

Smith, G B; Isaacs, R; Andrews, L; Wee, M Y K; van Teijlingen, E; Bick, D E; Hundley, V

2017-05-01

Obstetric early warning systems are recommended for monitoring hospitalised pregnant and postnatal women. We decided to compare: (i) vital sign values used to define physiological normality; (ii) symptoms and signs used to escalate care; (iii) type of chart used; and (iv) presence of explicit instructions for escalating care. One-hundred-and-twenty obstetric early warning charts and escalation protocols were obtained from consultant-led maternity units in the UK and Channel Islands. These data were extracted: values used to determine normality for each maternal vital sign; chart colour-coding; instructions following early warning system triggering; other criteria used as triggers. There was considerable variation in the charts, warning systems and escalation protocols. Of 120 charts, 89.2% used colour; 69.2% used colour-coded escalation systems. Forty-one (34.2%) systems required the calculation of weighted scores. Seventy-five discrete combinations of 'normal' vital sign ranges were found, the most common being: heart rate=50-99beats/min; respiratory rate=11-20breaths/min; blood pressure, systolic=100-149mmHg, diastolic ≤89mmHg; SpO 2 =95-100%; temperature=36.0-37.9°C; and Alert-Voice-Pain-Unresponsive assessment=Alert. Most charts (90.8%) provided instructions about who to contact following triggering, but only 41.7% gave instructions about subsequent observation frequency. The wide range of 'normal' vital sign values in different systems suggests a lack of equity in the processes for detecting deterioration and escalating care in hospitalised pregnant and postnatal women. Agreement regarding 'normal' vital sign ranges is urgently required and would assist the development of a standardised obstetric early warning system and chart. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gradual escalation of use-of-force reduces police officer injury.

PubMed

Jetelina, Katelyn K; Reingle Gonzalez, Jennifer M; Bishopp, Stephen A

2018-02-01

To examine how escalation through the force continuum predicts officer injury in the presence of citizen aggression, while controlling for extraneous factors, like citizen and officer characteristics. Cross-sectional data were extracted from 2244 use-of-force reports from the Dallas Police Department in 2015. Multilevel, mixed logistic regression models were used to evaluate the relationship between use of force and officer injury. Multilevel path analysis tested indirect and direct relationships between citizen aggression and officer injury. Results suggest that gradual escalation through the force continuum significantly decreases officer injury when a citizen is actively aggressive (β=-1.06, p value <0.001). Further, non-Hispanic black officers (β=-0.22, p value <0.001) and Hispanic officers (β=-0.08, p value <0.05) are less likely to gradually escalate through the force continuum, due to lower odds of verbal commands (black: OR=0.51, 95% CI 0.39 to 0.68; Hispanic: OR=0.77, 95% CI 0.60 to 0.99) and hard-empty hand control (black: OR=0.58, 95% CI 0.43 to 0.77) compared with white officers. Finally, officers with higher tenure (β=-0.01, p value <0.001) are less likely to gradually escalate through the force continuum. Escalation through the force continuum significantly reduces police officer injury. Future research should assess whether further environmental or situational factors contribute to the strong relationship between use of force and officer injury. Also, reliability and validity testing of use-of-force reports is an imperative direction for future research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Optically pre-amplified lidar-radar

NASA Astrophysics Data System (ADS)

Morvan, Loic; Dolfi, Daniel; Huignard, Jean-Pierre

2001-09-01

We present the concept of an optically pre-amplified intensity modulated lidar, where the modulation frequency is in the microwave domain (1-10 GHz). Such a system permits to combine directivity of laser beams with mature radar processing. As an intensity modulated or dual-frequency laser beam is directed on a target, the backscattered intensity is collected by an optical system, pass through an optical preamplifier, and is detected on a high speed photodiode in a direct detection scheme. A radar type processing permits then to extract range, speed and identification information. The association of spatially multimode amplifier and direct detection allows low sensitivity to atmospheric turbulence and large field of view. We demonstrated theoretically that optical pre-amplification can greatly enhance sensitivity, even in spatially multimode amplifiers, such as free-space amplifier or multimode doped fiber. Computed range estimates based on this concept are presented. Laboratory demonstrations using 1 to 3 GHz modulated laser sources and >20 dB gain in multimode amplifiers are detailed. Preliminary experimental results on range and speed measurements and possible use for large amplitude vibrometry will be presented.

the role of shock waves in modulation of galactic cosmic rays

NASA Technical Reports Server (NTRS)

Gall, R.; Thomas, B. T.; Durand, H.

1985-01-01

The understanding of modulation of the galactic cosmic rays has considerably progressed by the exploration by space probes of major heliospheric structures, such as the Corotating Interaction Regions, the neutral sheet, and the compression regions of intense heliospheric magnetic fields. Also relevant in this context were the detections in the outer heliosphere of long lasting Forbush type decreases of cosmic ray intensity. The results of recent theoretical studies on the changes in intensity and energy, at different location from the Sun, induced by the passage of shocks across the heliosphere are presented. In this version of the research, the simplest cases of modulation of uGV and 2GV particles by single or several shocks during periods of positive and negative solar field polarity are reviewed. The results of the theoretical aspects of the search is reported. The comparison of the theoretical predictions with space probe data allows conclusions to be drawn on the role of shocks on the modulation on both the 11 and 22 year galactic cosmic ray cycles in the outer heliosphere and on the plausibility of the models and parameters used.

Mueller-Stokes characterization and optimization of a liquid crystal on silicon display showing depolarization.

PubMed

Márquez, A; Moreno, I; Iemmi, C; Lizana, A; Campos, J; Yzuel, M J

2008-02-04

In this paper we characterize the polarimetric properties of a liquid crystal on silicon display (LCoS), including depolarization and diattenuation which are usually not considered when applying the LCoS in diffractive or adaptive optics. On one hand, we have found that the LCoS generates a certain degree (that can be larger than a 10%) of depolarized light, which depends on the addressed gray level and on the incident state of polarization (SOP), and can not be ignored in the above mentioned applications. The main origin of the depolarized light is related with temporal fluctuations of the SOP of the light reflected by the LCoS. The Mueller matrix of the LCoS is measured as a function of the gray level, which enables for a numerical optimization of the intensity modulation configurations. In particular we look for maximum intensity contrast modulation or for constant intensity modulation. By means of a heuristic approach we show that, using elliptically polarized light, amplitude-mostly or phase-mostly modulation can be obtained at a wavelength of 633 nm.

Subcarrier intensity modulation for MIMO visible light communications

NASA Astrophysics Data System (ADS)

Celik, Yasin; Akan, Aydin

2018-04-01

In this paper, subcarrier intensity modulation (SIM) is investigated for multiple-input multiple-output (MIMO) visible light communication (VLC) systems. A new modulation scheme called DC-aid SIM (DCA-SIM) is proposed for the spatial modulation (SM) transmission plan. Then, DCA-SIM is extended for multiple subcarrier case which is called DC-aid Multiple Subcarrier Modulation (DCA-MSM). Bit error rate (BER) performances of the considered system are analyzed for different MIMO schemes. The power efficiencies of DCA-SIM and DCA-MSM are shown in correlated MIMO VLC channels. The upper bound BER performances of the proposed models are obtained analytically for PSK and QAM modulation types in order to validate the simulation results. Additionally, the effect of power imbalance method on the performance of SIM is studied and remarkable power gains are obtained compared to the non-power imbalanced cases. In this work, Pulse amplitude modulation (PAM) and MSM-Index are used as benchmarks for single carrier and multiple carrier cases, respectively. And the results show that the proposed schemes outperform PAM and MSM-Index for considered single carrier and multiple carrier communication scenarios.

Does aging with a cortical lesion increase fall-risk: Examining effect of age versus stroke on intensity modulation of reactive balance responses from slip-like perturbations.

PubMed

Patel, Prakruti J; Bhatt, Tanvi

2016-10-01

We examined whether aging with and without a cerebral lesion such as stroke affects modulation of reactive balance response for recovery from increasing intensity of sudden slip-like stance perturbations. Ten young adults, older age-match adults and older chronic stroke survivors were exposed to three different levels of slip-like perturbations, level 1 (7.75m/s(2)), Level II (12.00m/s(2)) and level III (16.75m/s(2)) in stance. The center of mass (COM) state stability was computed as the shortest distance of the instantaneous COM position and velocity relative to base of support (BOS) from a theoretical threshold for backward loss of balance (BLOB). The COM position (XCOM/BOS) and velocity (ẊCOM/BOS) relative to BOS at compensatory step touchdown, compensatory step length and trunk angle at touchdown were also recorded. At liftoff, stability reduced with increasing perturbation intensity across all groups (main effect of intensity p<0.05). At touchdown, while the young group showed a linear improvement in stability with increasing perturbation intensity, such a trend was absent in other groups (intensity×group interaction, p<0.05). Between-group differences in stability at touchdown were thus observed at levels II and III. Further, greater stability at touchdown positively correlated with anterior XCOM/BOS however not with ẊCOM/BOS. Young adults maintained anterior XCOM/BOS by increasing compensatory step length and preventing greater trunk extension at higher perturbation intensities. The age-match group attempted to increase step length from intensity I to II to maintain stability however could not further increase step length at intensity III, resulting in lower stability on this level compared with the young group. Stroke group on the other hand was unable to modulate compensatory step length or control trunk extension at higher perturbation intensities resulting in reduced stability on levels II and III compared with the other groups. The findings reflect impaired modulation of recovery response with increasing intensity of sudden perturbations among stroke survivors compared with their healthy counter parts. Thus, aging superimposed with a cortical lesion could further impair reactive balance control, potentially contributing toward a higher fall risk in older stroke survivors. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Solar modulation of cosmic ray intensity and solar flare events inferred from (14)C contents in dated tree rings

NASA Technical Reports Server (NTRS)

Fan, C. Y.; Chen, T. M.; Yun, S. X.; Dai, K. M.

1985-01-01

The delta 14C values in 42 rings of a white spruce grown in Mackenzie Delta was measured as a continuing effort of tracing the history of solar modulation of cosmic ray intensity. The delta 14C values in six rings were measured, in search of a 14C increase due to two large solar flares that occurred in 1942. The results are presented.

Electric field-induced emission enhancement and modulation in individual CdSe nanowires.

PubMed

Vietmeyer, Felix; Tchelidze, Tamar; Tsou, Veronica; Janko, Boldizsar; Kuno, Masaru

2012-10-23

CdSe nanowires show reversible emission intensity enhancements when subjected to electric field strengths ranging from 5 to 22 MV/m. Under alternating positive and negative biases, emission intensity modulation depths of 14 ± 7% are observed. Individual wires are studied by placing them in parallel plate capacitor-like structures and monitoring their emission intensities via single nanostructure microscopy. Observed emission sensitivities are rationalized by the field-induced modulation of carrier detrapping rates from NW defect sites responsible for nonradiative relaxation processes. The exclusion of these states from subsequent photophysics leads to observed photoluminescence quantum yield enhancements. We quantitatively explain the phenomenon by developing a kinetic model to account for field-induced variations of carrier detrapping rates. The observed phenomenon allows direct visualization of trap state behavior in individual CdSe nanowires and represents a first step toward developing new optical techniques that can probe defects in low-dimensional materials.

Retention of drug administration skills after intensive teaching.

PubMed

Wheeler, D W; Degnan, B A; Murray, L J; Dunling, C P; Whittlestone, K D; Wood, D F; Smith, H L; Gupta, A K

2008-04-01

We have identified deficiencies in medical students' drug administration skills, and we attempted to address them with interactive online teaching modules and simulated critical incident scenarios. Short-term improvements have been evident with this intensive effort, but medium-term retention of skills has not been measured. A drug administration lecture, an online module and a simulated emergency scenario were offered to final year clinical students. None of the teaching was compulsory but participation was recorded, along with students' simulator performances and marks in an objective structured practical examination 9 months later. A poor simulator score predicted a poor performance in the later examination. Participation in the simulated scenario only significantly improved examination scores when supplemented by online teaching (p = 0.002). Intensive drug administration teaching using an online module and high fidelity simulation improves drug administration skills in the medium term. Students found simulation much more engaging than online teaching.

Sparing functional anatomical structures during intensity-modulated radiotherapy: an old problem, a new solution.

PubMed

Tan, Wenyong; Han, Guang; Wei, Shaozhong; Hu, Desheng

2014-08-01

During intensity-modulated radiotherapy, an organ is usually assumed to be functionally homogeneous and, generally, its anatomical and spatial heterogeneity with respect to radiation response are not taken into consideration. However, advances in imaging and radiation techniques as well as an improved understanding of the radiobiological response of organs have raised the possibility of sparing the critical functional structures within various organs at risk during intensity-modulated radiotherapy. Here, we discuss these structures, which include the critical brain structure, or neural nuclei, and the nerve fiber tracts in the CNS, head and neck structures related to radiation-induced salivary and swallowing dysfunction, and functional structures in the heart and lung. We suggest that these structures can be used as potential surrogate organs at risk in order to minimize their radiation dose and/or irradiated volume without compromising the dose coverage of the target volume during radiation treatment.

Apparatus and method for measuring single cell and sub-cellular photosynthetic efficiency

DOEpatents

Davis, Ryan Wesley; Singh, Seema; Wu, Huawen

2013-07-09

Devices for measuring single cell changes in photosynthetic efficiency in algal aquaculture are disclosed that include a combination of modulated LED trans-illumination of different intensities with synchronized through objective laser illumination and confocal detection. Synchronization and intensity modulation of a dual illumination scheme were provided using a custom microcontroller for a laser beam block and constant current LED driver. Therefore, single whole cell photosynthetic efficiency, and subcellular (diffraction limited) photosynthetic efficiency measurement modes are permitted. Wide field rapid light scanning actinic illumination is provided for both by an intensity modulated 470 nm LED. For the whole cell photosynthetic efficiency measurement, the same LED provides saturating pulses for generating photosynthetic induction curves. For the subcellular photosynthetic efficiency measurement, a switched through objective 488 nm laser provides saturating pulses for generating photosynthetic induction curves. A second near IR LED is employed to generate dark adapted states in the system under study.

Observed and Projected Droughts Conditioned on Temperature Change

NASA Astrophysics Data System (ADS)

Chiang, F.; AghaKouchak, A.; Mazdiyasni, O.

2016-12-01

Droughts have had severe urban, agricultural and wildlife impacts in historical and recent years. In addition, during times of water scarcity, heat stress has been shown to produce compounding climatic and environmental effects. Understanding the overall conditions associated with drought intensities is important for mapping the anatomy of the climate in the changing world. For the study, we evaluated the relationship drought severity has exhibited with temperature shifts between observed periods and also between an ensemble of BCSD downscaled CMIP5 projected and historically modeled datasets. We compared temperatures during different categories of drought severity on a monthly scale, and mapped areas displaying an escalation of temperature with stricter definitions of drought. A historical shift of warmer temperatures in more severe droughts was observed most consistently in Southwestern and Eastern states between the later half of the 20th century and a reference period of the early half of the 20th century. Future projections from an ensemble of CMIP5 models also showed a shift to warmer temperatures during more intense drought events in similar states. Preliminary statistics show that in many areas future droughts will be warmer that the average projected climate. These observed and forecasted shifts in the heating intensity of severe drought events underscore the need to further research these patterns and relationships both spatially and temporally.

Fixed or adapted conditioning intensity for repeated conditioned pain modulation.

PubMed

Hoegh, M; Petersen, K K; Graven-Nielsen, T

2017-12-29

Aims Conditioned pain modulation (CPM) is used to assess descending pain modulation through a test stimulation (TS) and a conditioning stimulation (CS). Due to potential carry-over effects, sequential CPM paradigms might alter the intensity of the CS, which potentially can alter the CPM-effect. This study aimed to investigate the difference between a fixed and adaptive CS intensity on CPM-effect. Methods On the dominant leg of 20 healthy subjects the cuff pressure detection threshold (PDT) was recorded as TS and the pain tolerance threshold (PTT) was assessed on the non-dominant leg for estimating the CS. The difference in PDT before and during CS defined the CPM-effect. The CPM-effect was assessed four times using a CS with intensities of 70% of baseline PTT (fixed) or 70% of PTT measured throughout the session (adaptive). Pain intensity of the conditioning stimulus was assessed on a numeric rating scale (NRS). Data were analyzed with repeated-measures ANOVA. Results No difference was found comparing the four PDTs assessed before CSs for the fixed and the adaptive paradigms. The CS pressure intensity for the adaptive paradigm was increasing during the four repeated assessments (P < 0.01). The pain intensity was similar during the fixed (NRS: 5.8±0.5) and the adjusted paradigm (NRS: 6.0±0.4). The CPM-effect was higher using the fixed condition compared with the adaptive condition (P < 0.05). Conclusions The current study found that sequential CPM paradigms using a fixed conditioning stimulus produced an increased CPM-effect compared with adaptive and increasing conditioning intensities.

MEOSAR Cost Escalation Risk

DTIC Science & Technology

2014-02-25

CMA, of Directorate of Costing Services, (D Cost S), requested DRDC CORA’s assistance with determining the cost escalation risk for the Medium Earth...Orbit Search and Rescue (MEOSAR) project. Following a project meeting on 12 February 2014, Mr. Iburg provided us with subject matter expert(s) (SME) cost

78 FR 32294 - Escalate Capital Partners SBIC I, L.P., License No. 06/06-0335; Notice Seeking Exemption Under...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

..., L.P. proposes to provide loan financing to SailPoint Technologies, Inc., 6034 West Courtyard Drive... Associate of Escalate Capital Partners, SBIC I, L.P., owns more than ten percent of SailPoint Technologies...

29 CFR 1917.116 - Elevators and escalators.

Code of Federal Regulations, 2010 CFR

2010-07-01

... or more floors of a structure. The term excludes such devices as conveyors, tiering or piling... devices shall not be overridden or made inoperable. (e) Elevators and escalators shall be thoroughly... shall be conducted by designated persons. Records of the results of the latest annual elevator...

Exciton Emission Intensity Modulation of Monolayer MoS2 via Au Plasmon Coupling

PubMed Central

Mukherjee, B.; Kaushik, N.; Tripathi, Ravi P. N.; Joseph, A. M.; Mohapatra, P. K.; Dhar, S.; Singh, B. P.; Kumar, G. V. Pavan; Simsek, E.; Lodha, S.

2017-01-01

Modulation of photoluminescence of atomically thin transition metal dichalcogenide two-dimensional materials is critical for their integration in optoelectronic and photonic device applications. By coupling with different plasmonic array geometries, we have shown that the photoluminescence intensity can be enhanced and quenched in comparison with pristine monolayer MoS2. The enhanced exciton emission intensity can be further tuned by varying the angle of polarized incident excitation. Through controlled variation of the structural parameters of the plasmonic array in our experiment, we demonstrate modulation of the photoluminescence intensity from nearly fourfold quenching to approximately threefold enhancement. Our data indicates that the plasmonic resonance couples to optical fields at both, excitation and emission bands, and increases the spontaneous emission rate in a double spacing plasmonic array structure as compared with an equal spacing array structure. Furthermore our experimental results are supported by numerical as well as full electromagnetic wave simulations. This study can facilitate the incorporation of plasmon-enhanced transition metal dichalcogenide structures in photodetector, sensor and light emitter applications. PMID:28134260

Older adult falls at a metropolitan airport: 2009-2010.

PubMed

Howland, Jonathan; Bibi, Salma; English, James; Dyer, Sophia; Peterson, Elizabeth W

2012-04-01

We investigated falls at a metropolitan airport to determine fall incidence, identify potential causes of these falls, and suggest opportunities for mitigation. We used deidentified incident reports of all falls requiring EMS response that occurred at the airport during 2009 and 2010. On average, one fall occurred every 2.3days. Ninety-six percent (96%) of falls occurred in terminals. Of all falls, 44% occurred on escalators, making escalators the most common location. Seventy-two percent (72%) of fallers were females; 43% were ≥65years; 92% of all falls resulted in a documented injury; 37% of falls resulted in transport to hospital emergency departments. Escalator fall risks include carrying bags (due to changes in baggage fees), using cells phones, not using handrails, and compromised strength and balance. Diverting at-risk passengers to elevators could significantly reduce the overall falls. Interventions targeting escalator falls have the greatest promise for reducing falls at this airport. Copyright © 2012 National Safety Council and Elsevier Ltd. All rights reserved.

Maternal Depression and Trait Anger as Risk Factors for Escalated Physical Discipline

PubMed Central

Shay, Nicole L.; Knutson, John F.

2008-01-01

To test the hypothesized anger-mediated relation between maternal depression and escalation of physical discipline, 122 economically disadvantaged mothers were assessed for current and lifetime diagnoses of depression using the Current Depressive Episode, Past Depression, and Dysthymia sections of the Structured Clinical Interview for DSM-IV (SCID) and a measure of current depressive symptoms, the Beck Depression Inventory–Second Edition (BDI-II). Escalation of physical discipline was assessed using a video analog parenting task; maternal anger not specific to discipline was assessed using the Spielberger Trait Anger Expression Inventory. Reports of anger were associated with the diagnosis of depression and depressive symptoms. Bootstrap analyses of indirect effects indicated that the link between depression and escalated discipline was mediated by anger. Parallel analyses based on BDI-II scores identified a marginally significant indirect effect of depression on discipline. Findings suggest that anger and irritability are central to the putative link between depression and harsh discipline. PMID:18174347

The effects of mortality salience on escalation of commitment.

PubMed

Yen, Chih-Long; Lin, Chun-Yu

2012-01-01

Based on propositions derived from terror management theory (TMT), the current study proposes that people who are reminded of their mortality exhibit a higher degree of self-justification behavior to maintain their self-esteem. For this reason, they could be expected to stick with their previous decisions and invest an increasing amount of resources in those decisions, despite the fact that negative feedback has clearly indicated that they might be on a course toward failure (i.e., "escalation of commitment"). Our experiment showed that people who were reminded of their mortality were more likely to escalate their level of commitment by maintaining their current course of action. Two imaginary scenarios were tested. One of the scenarios involved deciding whether to send additional troops into the battlefield when previous attempts had failed; the other involved deciding whether to continue developing an anti-radar fighter plane when the enemy had already developed a device to detect it. The results supported our hypothesis that mortality salience increases the tendency to escalate one's level of commitment.

Prioritising Responses Of Nurses To deteriorating patient Observations (PRONTO) protocol: testing the effectiveness of a facilitation intervention in a pragmatic, cluster-randomised trial with an embedded process evaluation and cost analysis.

PubMed

Bucknall, Tracey K; Harvey, Gill; Considine, Julie; Mitchell, Imogen; Rycroft-Malone, Jo; Graham, Ian D; Mohebbi, Mohammadreza; Watts, Jennifer; Hutchinson, Alison M

2017-07-11

Vital signs are the primary indicator of physiological status and for determining the need for urgent clinical treatment. Yet, if physiological signs of deterioration are missed, misinterpreted or mismanaged, then critical illness, unplanned intensive care admissions, cardiac arrest and death may ensue. Although evidence demonstrates the benefit of early recognition and management of deteriorating patients, failure to escalate care and manage deteriorating patients remains a relatively frequent occurrence in hospitals. A pragmatic cluster-randomised controlled trial design will be used to measure clinical effectiveness and cost of a facilitation intervention to improve nurses' vital sign measurement, interpretation, treatment and escalation of care for patients with abnormal vital signs. A cost consequence analysis will evaluate the intervention cost and effectiveness, and a process evaluation will determine how the implementation of the intervention contributes to outcomes. We will compare clinical outcomes and costs from standard implementation of clinical practice guidelines (CPGs) to facilitated implementation of CPGs. The primary outcome will be adherence to the CPGs by nurses, as measured by escalation of care as per organisational policy. The study will be conducted in four Australian major metropolitan teaching hospitals. In each hospital, eight to ten wards will be randomly allocated to intervention and control groups. Control wards will receive standard implementation of CPGs, while intervention wards will receive standard CPG implementation plus facilitation, using facilitation methods and processes tailored to the ward context. The intervention will be administered to all nursing staff at the ward level for 6 months. At each hospital, two types of facilitators will be provided: a hospital-level facilitator as the lead; and two ward-level facilitators for each ward. This study uses an innovative, networked approach to facilitation to enable uptake of CPGs. Findings will inform the intervention utility and knowledge translation measurement approaches. If successful, the study methodology and intervention has potential for translation to other health care standards. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12616000544471p.

Primary treatments for clinically localized prostate cancer: a comprehensive lifetime cost-utility analysis

PubMed Central

Cooperberg, Matthew R.; Ramakrishna, Naren R.; Duff, Steven B.; Hughes, Kathleen E.; Sadownik, Sara; Smith, Joseph A.; Tewari, Ashutosh K.

2012-01-01

Objectives To characterize the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (dose-escalated 3-dimensional conformal radiation, intensity-modulated radiation, brachytherapy, or combination), using a comprehensive, lifetime decision analytic model. Patients and Methods A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes following primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. Patients could experience remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the U.S. payer perspective, with incorporation of patient costs in a sensitivity analysis. Results Differences in quality-adjusted life years across modalities were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6 to 10.5 for intermediate-risk patients, and 7.8 to 9.3 for high-risk patients. There were no statistically significant differences among surgical modalities, which tended to be more effective than radiation modalities, with the exception of combination external beam + brachytherapy for high-risk disease. Radiation modalities were consistently more expensive than surgical modalities; costs ranged from $19,901 (robot-assisted prostatectomy for low-risk disease) to $50,276 (combination radiation for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Conclusions Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions regarding strategies to improve efficiency of treatment selection for localized prostate cancer. PMID:23279038

Radiobiological impact of reduced margins and treatment technique for prostate cancer in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP).

PubMed

Jensen, Ingelise; Carl, Jesper; Lund, Bente; Larsen, Erik H; Nielsen, Jane

2011-01-01

Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on the Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications. Copyright © 2011 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Evaluation of the radiobiological gamma index with motion interplay in tangential IMRT breast treatment

PubMed Central

Sumida, Iori; Yamaguchi, Hajime; Das, Indra J.; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Tamari, Kiesuke; Suzuki, Osamu; Seo, Yuji; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko

2016-01-01

The purpose of this study was to evaluate the impact of the motion interplay effect in early-stage left-sided breast cancer intensity-modulated radiation therapy (IMRT), incorporating the radiobiological gamma index (RGI). The IMRT dosimetry for various breathing amplitudes and cycles was investigated in 10 patients. The predicted dose was calculated using the convolution of segmented measured doses. The physical gamma index (PGI) of the planning target volume (PTV) and the organs at risk (OAR) was calculated by comparing the original with the predicted dose distributions. The RGI was calculated from the PGI using the tumor control probability (TCP) and the normal tissue complication probability (NTCP). The predicted mean dose and the generalized equivalent uniform dose (gEUD) to the target with various breathing amplitudes were lower than the original dose (P < 0.01). The predicted mean dose and gEUD to the OARs with motion were higher than for the original dose to the OARs (P < 0.01). However, the predicted data did not differ significantly between the various breathing cycles for either the PTV or the OARs. The mean RGI gamma passing rate for the PTV was higher than that for the PGI (P < 0.01), and for OARs, the RGI values were higher than those for the PGI (P < 0.01). The gamma passing rates of the RGI for the target and the OARs other than the contralateral lung differed significantly from those of the PGI under organ motion. Provided an NTCP value <0.05 is considered acceptable, it may be possible, by taking breathing motion into consideration, to escalate the dose to achieve the PTV coverage without compromising the TCP. PMID:27534793

Linear optical pulse compression based on temporal zone plates.

PubMed

Li, Bo; Li, Ming; Lou, Shuqin; Azaña, José

2013-07-15

We propose and demonstrate time-domain equivalents of spatial zone plates, namely temporal zone plates, as alternatives to conventional time lenses. Both temporal intensity zone plates, based on intensity-only temporal modulation, and temporal phase zone plates, based on phase-only temporal modulation, are introduced and studied. Temporal zone plates do not exhibit the limiting tradeoff between temporal aperture and frequency bandwidth (temporal resolution) of conventional linear time lenses. As a result, these zone plates can be ideally designed to offer a time-bandwidth product (TBP) as large as desired, practically limited by the achievable temporal modulation bandwidth (limiting the temporal resolution) and the amount of dispersion needed in the target processing systems (limiting the temporal aperture). We numerically and experimentally demonstrate linear optical pulse compression by using temporal zone plates based on linear electro-optic temporal modulation followed by fiber-optics dispersion. In the pulse-compression experiment based on temporal phase zone plates, we achieve a resolution of ~25.5 ps over a temporal aperture of ~5.77 ns, representing an experimental TBP larger than 226 using a phase-modulation amplitude of only ~0.8π rad. We also numerically study the potential of these devices to achieve temporal imaging of optical waveforms and present a comparative analysis on the performance of different temporal intensity and phase zone plates.

Gas sensing using wavelength modulation spectroscopy

NASA Astrophysics Data System (ADS)

Viveiros, D.; Ribeiro, J.; Flores, D.; Ferreira, J.; Frazao, O.; Santos, J. L.; Baptista, J. M.

2014-08-01

An experimental setup has been developed for different gas species sensing based on the Wavelength Modulation Spectroscopy (WMS) principle. The target is the measurement of ammonia, carbon dioxide and methane concentrations. The WMS is a rather sensitive technique for detecting atomic/molecular species presenting the advantage that it can be used in the near-infrared region using optical telecommunications technology. In this technique, the laser wavelength and intensity are modulated applying a sine wave signal through the injection current, which allows the shift of the detection bandwidth to higher frequencies where laser intensity noise is reduced. The wavelength modulated laser light is tuned to the absorption line of the target gas and the absorption information can be retrieved by means of synchronous detection using a lock-in amplifier, where the amplitude of the second harmonic of the laser modulation frequency is proportional to the gas concentration. The amplitude of the second harmonic is normalised by the average laser intensity and detector gain through a LabVIEW® application, where the main advantage of normalising is that the effects of laser output power fluctuations and any variations in laser transmission, or optical-electrical detector gain are eliminated. Two types of sensing heads based on free space light propagation with different optical path length were used, permitting redundancy operation and technology validation.

The "new" military and income inequality: A cross national analysis.

PubMed

Kentor, Jeffrey; Jorgenson, Andrew K; Kick, Edward

2012-05-01

Military expenditures have escalated over the last three decades in both developed and less developed countries, without a corresponding expansion of military personnel. Spending has instead been directed towards hi-tech weaponry, what we refer to as the "new" military. We hypothesize that this new, increasingly capital-intensive military is no longer a pathway of upward mobility or employer of last resort for many uneducated, unskilled, or unemployed people, with significant consequences for those individuals and society as a whole. One such consequence, we argue, is an increase in income inequality. We test this hypothesis with cross-national panel models, estimated for 82 developed and less developed countries from 1970 to 2000. Findings indicate that military capital-intensiveness, as measured by military expenditures per soldier, exacerbates income inequality net of control variables. Neither total military expenditures/GDP nor military participation has a significant effect. It appears from these findings that today's "new" military establishment is abrogating its historical role as an equalizing force in society, with important policy implications. Copyright © 2011 Elsevier Inc. All rights reserved.

Chapter 6. Protection of patients and staff during a pandemic. Recommendations and standard operating procedures for intensive care unit and hospital preparations for an influenza epidemic or mass disaster.

PubMed

Taylor, Bruce L; Montgomery, Hugh E; Rhodes, Andrew; Sprung, Charles L

2010-04-01

To provide recommendations and standard operating procedures (SOPs) for intensive care unit (ICU) and hospital preparations for an influenza pandemic or mass disaster with a specific focus on protection of patients and staff. Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including protection of patients and staff. Key recommendations include: (1) prepare infection control and occupational health policies for clinical risks relating to potential disease transmission; (2) decrease clinical risks and provide adequate facilities through advanced planning to maximise capacity by increasing essential equipment, drugs, supplies and encouraging staff availability; (3) create robust systems to maintain staff confidence and safety by minimising non-clinical risks and maintaining or escalating essential services; (4) prepare formal reassurance plans for legal protection; (5) provide assistance to staff working outside their normal domains. Judicious planning and adoption of protocols for protection of patients and staff are necessary to optimise outcomes during a pandemic.

Lower light intensity reduces larval aggression in matrinxã, Brycon amazonicus.

PubMed

Lopes, Ana Caroliny C; Villacorta-Correa, Marle Angélica; Carvalho, Thaís B

2018-06-01

Brycon amazonicus shows a high frequency of aggressive behavior, which can be a limiting factor in intensive farming systems. Environmental changes can modulate the social interactions of fish and reduce aggression during the different stages of production. Groups of three larvae at 12 h after hatching (HAH) were subjected to different levels of light intensity: low (17 ± 3 lx), intermediate (204 ± 12.17 lx) and high (1,613.33 ± 499.03 lx), with eight replicates for each level. The lower light intensity reduced the frequency of aggressive interactions and locomotor activity exhibited by the animals. Based on these results, light intensity modulates aggression in B. amazonicus larvae. Manipulation of this factor could improve the social conditions of this species during farming and contribute to the development of new production technologies. Copyright © 2018 Elsevier B.V. All rights reserved.

14 CFR 1214.803 - Reimbursement policy.

Code of Federal Regulations, 2012 CFR

2012-01-01

... operations will be developed after NASA has obtained more operational experience. (b) Escalation. Payments shall be escalated in accordance with the Shuttle policy. (c) Customers shall reimburse NASA an amount... reimburse NASA for standard Spacelab services an amount which is a pro rata share of: (i) The appropriate...

14 CFR 1214.803 - Reimbursement policy.

Code of Federal Regulations, 2013 CFR

2013-01-01

... operations will be developed after NASA has obtained more operational experience. (b) Escalation. Payments shall be escalated in accordance with the Shuttle policy. (c) Customers shall reimburse NASA an amount... reimburse NASA for standard Spacelab services an amount which is a pro rata share of: (i) The appropriate...

14 CFR § 1214.803 - Reimbursement policy.

Code of Federal Regulations, 2014 CFR

2014-01-01

... operations will be developed after NASA has obtained more operational experience. (b) Escalation. Payments shall be escalated in accordance with the Shuttle policy. (c) Customers shall reimburse NASA an amount... reimburse NASA for standard Spacelab services an amount which is a pro rata share of: (i) The appropriate...

14 CFR 1214.803 - Reimbursement policy.

Code of Federal Regulations, 2011 CFR

2011-01-01

... operations will be developed after NASA has obtained more operational experience. (b) Escalation. Payments shall be escalated in accordance with the Shuttle policy. (c) Customers shall reimburse NASA an amount... reimburse NASA for standard Spacelab services an amount which is a pro rata share of: (i) The appropriate...

Escalating Commitment to a Relationship: The Sexual Harassment Trap.

ERIC Educational Resources Information Center

Williams, Karen B.; Cyr, Ramona R.

1992-01-01

Studies divergent sexual harassment perceptions in a case of a perpetrator's gradual sexual advancements and a target's escalating commitment to their relationship, using 60 male and 60 female undergraduates. Males' ratings of sexual harassment decreased when female target participated in increasingly informal friendly interactions. Females'…

Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

NASA Astrophysics Data System (ADS)

Weinberg, Rebecca

The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity.

Neonatal Early Warning Tools for recognising and responding to clinical deterioration in neonates cared for in the maternity setting: A retrospective case-control study.

PubMed

Paliwoda, Michelle; New, Karen; Bogossian, Fiona

2016-09-01

All newborns are at risk of deterioration as a result of failing to make the transition to extra uterine life. Signs of deterioration can be subtle and easily missed. It has been postulated that the use of an Early Warning Tool may assist clinicians in recognising and responding to signs of deterioration earlier in neonates, thereby preventing a serious adverse event. To examine whether observations from a Standard Observation Tool, applied to three neonatal Early Warning Tools, would hypothetically trigger an escalation of care more frequently than actual escalation of care using the Standard Observation Tool. A retrospective case-control study. A maternity unit in a tertiary public hospital in Australia. Neonates born in 2013 of greater than or equal to 34(+0) weeks gestation, admitted directly to the maternity ward from their birthing location and whose subsequent deterioration required admission to the neonatal unit, were identified as cases from databases of the study hospital. Each case was matched with three controls, inborn during the same period and who did not experience deterioration and neonatal unit admission. Clinical and physiological data recorded on a Standard Observation Tool, from time of admission to the maternity ward, for cases and controls were charted onto each of three Early Warning Tools. The primary outcome was whether the tool 'triggered an escalation of care'. Descriptive statistics (n, %, Mean and SD) were employed. Cases (n=26) comprised late preterm, early term and post-term neonates and matched by gestational age group with 3 controls (n=78). Overall, the Standard Observation Tool triggered an escalation of care for 92.3% of cases compared to the Early Warning Tools; New South Wales Health 80.8%, United Kingdom Newborn Early Warning Chart 57.7% and The Australian Capital Territory Neonatal Early Warning Score 11.5%. Subgroup analysis by gestational age found differences between the tools in hypothetically triggering an escalation of care. The Standard Observation Tool triggered an escalation of care more frequently than the Early Warning Tools, which may be as a result of behavioural data captured on the Standard Observation Tool and escalated, which could not be on the Early Warning Tools. Findings demonstrate that a single tool applied to all gestational age ranges may not be effective in identifying early deterioration or may over trigger an escalation of care. Further research is required into the sensitivity and specificity of Early Warning Tools in neonatal sub-populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cross-Phase Modulation: A New Technique for Controlling the Spectral, Temporal, and Spatial Properties of Ultrashort Pulses

NASA Astrophysics Data System (ADS)

Baldeck, P. L.; Ho, P. P.; Alfano, Robert R.

Self-phase modulation (SPM) is the principal mechanism responsible for the generation of picosecond and femtosecond white-light supercontinua. When an intense ultrashort pulse progagates through a medium, it distorts the atomic configuration of the material, which changes the refractive index. The pulse phase is time modulated, which causes the generation of new frequencies. This phase modulation originates from the pulse itself (self-phase modulation). It can also be generated by a copropagating pulse (cross-phase modulation).

Potential role of hypoxia imaging using (18)F-FAZA PET to guide hypoxia-driven interventions (carbogen breathing or dose escalation) in radiation therapy.

PubMed

Tran, Ly-Binh-An; Bol, Anne; Labar, Daniel; Karroum, Oussama; Bol, Vanesa; Jordan, Bénédicte; Grégoire, Vincent; Gallez, Bernard

2014-11-01

Hypoxia-driven intervention (oxygen manipulation or dose escalation) could overcome radiation resistance linked to tumor hypoxia. Here, we evaluated the value of hypoxia imaging using (18)F-FAZA PET to predict the outcome and guide hypoxia-driven interventions. Two hypoxic rat tumor models were used: rhabdomyosarcoma and 9L-glioma. For the irradiated groups, the animals were divided into two subgroups: breathing either room air or carbogen. (18)F-FAZA PET images were obtained just before the irradiation to monitor the hypoxic level of each tumor. Absolute pO2 were also measured using EPR oximetry. Dose escalation was used in Rhabdomyosarcomas. For 9L-gliomas, a significant correlation between (18)F-FAZA T/B ratio and tumor growth delay was found; additionally, carbogen breathing dramatically improved the tumor response to irradiation. On the contrary, Rhabdomyosarcomas were less responsive to hyperoxic challenge. For that model, an increase in growth delay was observed using dose escalation, but not when combining irradiation with carbogen. (18)F-FAZA uptake may be prognostic of outcome following radiotherapy and could assess the response of tumor to carbogen breathing. (18)F-FAZA PET may help to guide the hypoxia-driven intervention with irradiation: carbogen breathing in responsive tumors or dose escalation in tumors non-responsive to carbogen. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Direct Observations of Parenting and Real-time Negative Affect among Adolescent Smokers and Non-Smokers

PubMed Central

Richmond, Melanie J.; Mermelstein, Robin J.; Wakschlag, Lauren S.

2012-01-01

Objective This longitudinal study examined how observations of parental general communication style and control with their adolescents predicted changes in negative affect over time for adolescent smokers and non-smokers. Method Participants were 9th and 10th grade adolescents (N = 111; 56.8% female) who had all experimented with cigarettes and were thus at risk for continued smoking and escalation; 36% of these adolescents (n = 40) had smoked in the past month at baseline and were considered smokers in the present analyses. Adolescents participated separately with mothers and fathers in observed parent-adolescent problem-solving discussions to assess parenting at baseline. Adolescent negative affect was assessed at baseline, 6- and 24-months via ecological momentary assessment. Results Among both smoking and non-smoking adolescents, escalating negative affect significantly increased risk for future smoking. Higher quality maternal and paternal communication predicted a decline in negative affect over 1.5 years for adolescent smokers but was not related to negative affect for non-smokers. Controlling maternal, but not paternal, parenting predicted escalation in negative affect for all adolescents. Conclusions Findings suggest that reducing negative affect among experimenting youth can reduce risk for smoking escalation. Therefore, family-based prevention efforts for adolescent smoking escalation might consider parental general communication style and control as intervention targets. However, adolescent smoking status and parent gender may moderate these effects. PMID:23153193

Direct observations of parenting and real-time negative affect among adolescent smokers and nonsmokers.

PubMed

Richmond, Melanie J; Mermelstein, Robin J; Wakschlag, Lauren S

2013-01-01

This longitudinal study examined how observations of parental general communication style and control with their adolescents predicted changes in negative affect over time for adolescent smokers and nonsmokers. Participants were 9th- and 10th-grade adolescents (N = 111; 56.8% female) who had all experimented with cigarettes and were thus at risk for continued smoking and escalation; 36% of these adolescents (n = 40) had smoked in the past month at baseline and were considered smokers in the present analyses. Adolescents participated separately with mothers and fathers in observed parent-adolescent problem-solving discussions to assess parenting at baseline. Adolescent negative affect was assessed at baseline, 6 months, and 24 months via ecological momentary assessment. Among both smoking and nonsmoking adolescents, escalating negative affect significantly increased risk for future smoking. Higher quality maternal and paternal communication predicted a decline in negative affect over 1.5 years for adolescent smokers but was not related to negative affect for nonsmokers. Controlling maternal, but not paternal, parenting predicted escalation in negative affect for all adolescents. Findings suggest that reducing negative affect among experimenting youth can reduce risk for smoking escalation. Therefore, family-based prevention efforts for adolescent smoking escalation might consider parental general communication style and control as intervention targets. However, adolescent smoking status and parent gender may moderate these effects.

Zeroth-order phase-contrast technique.

PubMed

Pizolato, José Carlos; Cirino, Giuseppe Antonio; Gonçalves, Cristhiane; Neto, Luiz Gonçalves

2007-11-01

What we believe to be a new phase-contrast technique is proposed to recover intensity distributions from phase distributions modulated by spatial light modulators (SLMs) and binary diffractive optical elements (DOEs). The phase distribution is directly transformed into intensity distributions using a 4f optical correlator and an iris centered in the frequency plane as a spatial filter. No phase-changing plates or phase dielectric dots are used as a filter. This method allows the use of twisted nematic liquid-crystal televisions (LCTVs) operating in the real-time phase-mostly regime mode between 0 and p to generate high-intensity multiple beams for optical trap applications. It is also possible to use these LCTVs as input SLMs for optical correlators to obtain high-intensity Fourier transform distributions of input amplitude objects.

Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The “La Cittadina Fondazione” Experience

PubMed Central

Dolera, Mario; Malfassi, Luca; Carrara, Nancy; Finesso, Sara; Marcarini, Silvia; Mazza, Giovanni; Pavesi, Simone; Sala, Massimo; Urso, Gaetano

2018-01-01

Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets. PMID:29364837

Apparatus and method for increasing the bandwidth of a laser beam

DOEpatents

Chaffee, Paul H.

1991-01-01

A method and apparatus is disclosed that provides a laser output beam having a broad bandwidth and an intensity smooth over time. The bandwidth of the laser output can be varied easily by varying the intensity of a broadband source. The present invention includes an optical modulation apparatus comprising a narrowband laser that outputs a horizontally polarized beam (a "signal beam") and a broadband laser that outputs a vertically polarized beam (a "pump beam") whose intensity varies rapidly. The two beam are coupled into a birefringent laser material so that the respective polarizations coincide with the principal axes of the material. As the two beams travel through the material, the polarization preserving properties of the birefringent material maintain the respective polarizations of the two beam; however there is coupling between the two beams as a result of cross phase modulations, which induces a bandwidth change of the signal beam. The amount of bandwidth change is dependent upon the average intensity of the pump beam. The beams are coupled out from the birefringent material and the modulated signal beam is separated by a polarization selector. The modulated signal beam now has a wider bandwidth, and its shape remains smooth in time. This signal beam can be applied to incoherence inducing systems. The different bandwidths required by these different incoherence inducing systems can be obtained by varying the intensity of the pump beam. The United States Government has rights in this invention pursuant to Contract No. W7405-ENG-48 between the United States Department of Energy and the University of California for the operation of Lawrence Livermore National Laboratory.

Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study

PubMed Central

Kinali, Maria; Arechavala-Gomeza, Virginia; Feng, Lucy; Cirak, Sebahattin; Hunt, David; Adkin, Carl; Guglieri, Michela; Ashton, Emma; Abbs, Stephen; Nihoyannopoulos, Petros; Garralda, Maria Elena; Rutherford, Mary; Mcculley, Caroline; Popplewell, Linda; Graham, Ian R; Dickson, George; Wood, Matthew JA; Wells, Dominic J; Wilton, Steve D; Kole, Ryszard; Straub, Volker; Bushby, Kate; Sewry, Caroline; Morgan, Jennifer E; Muntoni, Francesco

2009-01-01

Summary Background Mutations that disrupt the open reading frame and prevent full translation of DMD, the gene that encodes dystrophin, underlie the fatal X-linked disease Duchenne muscular dystrophy. Oligonucleotides targeted to splicing elements (splice switching oligonucleotides) in DMD pre-mRNA can lead to exon skipping, restoration of the open reading frame, and the production of functional dystrophin in vitro and in vivo, which could benefit patients with this disorder. Methods We did a single-blind, placebo-controlled, dose-escalation study in patients with DMD recruited nationally, to assess the safety and biochemical efficacy of an intramuscular morpholino splice-switching oligonucleotide (AVI-4658) that skips exon 51 in dystrophin mRNA. Seven patients with Duchenne muscular dystrophy with deletions in the open reading frame of DMD that are responsive to exon 51 skipping were selected on the basis of the preservation of their extensor digitorum brevis (EDB) muscle seen on MRI and the response of cultured fibroblasts from a skin biopsy to AVI-4658. AVI-4658 was injected into the EDB muscle; the contralateral muscle received saline. Muscles were biopsied between 3 and 4 weeks after injection. The primary endpoint was the safety of AVI-4658 and the secondary endpoint was its biochemical efficacy. This trial is registered, number NCT00159250. Findings Two patients received 0·09 mg AVI-4658 in 900 μL (0·9%) saline and five patients received 0·9 mg AVI-4658 in 900 μL saline. No adverse events related to AVI-4658 administration were reported. Intramuscular injection of the higher-dose of AVI-4658 resulted in increased dystrophin expression in all treated EDB muscles, although the results of the immunostaining of EDB-treated muscle for dystrophin were not uniform. In the areas of the immunostained sections that were adjacent to the needle track through which AVI-4658 was given, 44–79% of myofibres had increased expression of dystrophin. In randomly chosen sections of treated EDB muscles, the mean intensity of dystrophin staining ranged from 22% to 32% of the mean intensity of dystrophin in healthy control muscles (mean 26·4%), and the mean intensity was 17% (range 11–21%) greater than the intensity in the contralateral saline-treated muscle (one-sample paired t test p=0·002). In the dystrophin-positive fibres, the intensity of dystrophin staining was up to 42% of that in healthy muscle. We showed expression of dystrophin at the expected molecular weight in the AVI-4658-treated muscle by immunoblot. Interpretation Intramuscular AVI-4658 was safe and induced the expression of dystrophin locally within treated muscles. This proof-of-concept study has led to an ongoing systemic clinical trial of AVI-4658 in patients with DMD. Funding UK Department of Health. PMID:19713152

Racial Bias in Neural Response for Pain Is Modulated by Minimal Group

PubMed Central

Shen, Fengtao; Hu, Yang; Fan, Mingxia; Wang, Huimin; Wang, Zhaoxin

2018-01-01

Whether empathic racial bias could be modulated is a subject of intense interest. The present study was carried out to explore whether empathic racial bias for pain is modulated by minimal group. Chinese/Western faces with neutral expressions receiving painful (needle penetration) or non-painful (Q-tip touch) stimulation were presented. Participants were asked to rate the pain intensity felt by Chinese/Western models of ingroup/outgroup members. Their implicit racial bias were also measured. Two lines of evidence indicated that the anterior cingulate cortex (ACC) was modulated by racial bias: (1) Chinese models elicited stronger activity than Western did in the ACC, and (2) activity in the ACC was modulated by implicit racial bias. Whereas the right anterior insula (rAI) were modulated by ingroup bias, in which ingroup member elicited stronger activity than outgroup member did. Furthermore, activity in the ACC was modulated by activity of rAI (i.e., ingroup bias) in the pain condition, while activity in the rAI was modulated by activity of ACC (i.e., racial bias) in the nopain condition. Our results provide evidence that there are different neural correlates for racial bias and ingroup bias, and neural racial bias for pain can be modulated by minimal group. PMID:29379429

Racial Bias in Neural Response for Pain Is Modulated by Minimal Group.

PubMed

Shen, Fengtao; Hu, Yang; Fan, Mingxia; Wang, Huimin; Wang, Zhaoxin

2017-01-01

Whether empathic racial bias could be modulated is a subject of intense interest. The present study was carried out to explore whether empathic racial bias for pain is modulated by minimal group. Chinese/Western faces with neutral expressions receiving painful (needle penetration) or non-painful (Q-tip touch) stimulation were presented. Participants were asked to rate the pain intensity felt by Chinese/Western models of ingroup/outgroup members. Their implicit racial bias were also measured. Two lines of evidence indicated that the anterior cingulate cortex (ACC) was modulated by racial bias: (1) Chinese models elicited stronger activity than Western did in the ACC, and (2) activity in the ACC was modulated by implicit racial bias. Whereas the right anterior insula (rAI) were modulated by ingroup bias, in which ingroup member elicited stronger activity than outgroup member did. Furthermore, activity in the ACC was modulated by activity of rAI (i.e., ingroup bias) in the pain condition, while activity in the rAI was modulated by activity of ACC (i.e., racial bias) in the nopain condition. Our results provide evidence that there are different neural correlates for racial bias and ingroup bias, and neural racial bias for pain can be modulated by minimal group.

Electronic polarization-division demultiplexing based on digital signal processing in intensity-modulation direct-detection optical communication systems.

PubMed

Kikuchi, Kazuro

2014-01-27

We propose a novel configuration of optical receivers for intensity-modulation direct-detection (IM · DD) systems, which can cope with dual-polarization (DP) optical signals electrically. Using a Stokes analyzer and a newly-developed digital signal-processing (DSP) algorithm, we can achieve polarization tracking and demultiplexing in the digital domain after direct detection. Simulation results show that the power penalty stemming from digital polarization manipulations is negligibly small.

Computer Generated Holography with Intensity-Graded Patterns

PubMed Central

Conti, Rossella; Assayag, Osnath; de Sars, Vincent; Guillon, Marc; Emiliani, Valentina

2016-01-01

Computer Generated Holography achieves patterned illumination at the sample plane through phase modulation of the laser beam at the objective back aperture. This is obtained by using liquid crystal-based spatial light modulators (LC-SLMs), which modulate the spatial phase of the incident laser beam. A variety of algorithms is employed to calculate the phase modulation masks addressed to the LC-SLM. These algorithms range from simple gratings-and-lenses to generate multiple diffraction-limited spots, to iterative Fourier-transform algorithms capable of generating arbitrary illumination shapes perfectly tailored on the base of the target contour. Applications for holographic light patterning include multi-trap optical tweezers, patterned voltage imaging and optical control of neuronal excitation using uncaging or optogenetics. These past implementations of computer generated holography used binary input profile to generate binary light distribution at the sample plane. Here we demonstrate that using graded input sources, enables generating intensity graded light patterns and extend the range of application of holographic light illumination. At first, we use intensity-graded holograms to compensate for LC-SLM position dependent diffraction efficiency or sample fluorescence inhomogeneity. Finally we show that intensity-graded holography can be used to equalize photo evoked currents from cells expressing different levels of chanelrhodopsin2 (ChR2), one of the most commonly used optogenetics light gated channels, taking into account the non-linear dependence of channel opening on incident light. PMID:27799896

Scale-Up of the Electrodeposition of ZnO/Eosin Y Hybrid Thin Films for the Fabrication of Flexible Dye-Sensitized Solar Cell Modules.

PubMed

Bittner, Florian; Oekermann, Torsten; Wark, Michael

2018-02-02

The low-temperature fabrication of flexible ZnO photo-anodes for dye-sensitized solar cells (DSSCs) by templated electrochemical deposition of films was performed in an enlarged and technical simplified deposition setup to demonstrate the feasibility of the scale-up of the deposition process. After extraction of eosin Y (EY) from the initially deposited ZnO/EY hybrid films, mesoporous ZnO films with an area of about 40 cm² were reproducibly obtained on fluorine doped tin oxide (FTO)-glass as well as flexible indium tin oxide (ITO)-polyethylenterephthalate (PET) substrates. With a film thickness of up to 9 µm and a high specific surface area of up to about 77 m²·cm -3 the ZnO films on the flexible substrates show suitable properties for DSSCs. Operative flexible DSSC modules proved the suitability of the ZnO films for use as DSSC photo-anodes. Under a low light intensity of about 0.007 sun these modules achieved decent performance parameters with conversion efficiencies of up to 2.58%. With rising light intensity the performance parameters deteriorated, leading to conversion efficiencies below 1% at light intensities above 0.5 sun. The poor performance of the modules under high light intensities can be attributed to their high series resistances.

Scale-Up of the Electrodeposition of ZnO/Eosin Y Hybrid Thin Films for the Fabrication of Flexible Dye-Sensitized Solar Cell Modules

PubMed Central

Oekermann, Torsten

2018-01-01

The low-temperature fabrication of flexible ZnO photo-anodes for dye-sensitized solar cells (DSSCs) by templated electrochemical deposition of films was performed in an enlarged and technical simplified deposition setup to demonstrate the feasibility of the scale-up of the deposition process. After extraction of eosin Y (EY) from the initially deposited ZnO/EY hybrid films, mesoporous ZnO films with an area of about 40 cm2 were reproducibly obtained on fluorine doped tin oxide (FTO)-glass as well as flexible indium tin oxide (ITO)–polyethylenterephthalate (PET) substrates. With a film thickness of up to 9 µm and a high specific surface area of up to about 77 m2·cm−3 the ZnO films on the flexible substrates show suitable properties for DSSCs. Operative flexible DSSC modules proved the suitability of the ZnO films for use as DSSC photo-anodes. Under a low light intensity of about 0.007 sun these modules achieved decent performance parameters with conversion efficiencies of up to 2.58%. With rising light intensity the performance parameters deteriorated, leading to conversion efficiencies below 1% at light intensities above 0.5 sun. The poor performance of the modules under high light intensities can be attributed to their high series resistances. PMID:29393910

Simple Carotid-Sparing Intensity-Modulated Radiotherapy Technique and Preliminary Experience for T1-2 Glottic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, David I., E-mail: dirosenthal@mdanderson.or; Fuller, Clifton D.; Barker, Jerry L.

2010-06-01

Purpose: To investigate the dosimetry and feasibility of carotid-sparing intensity-modulated radiotherapy (IMRT) for early glottic cancer and to report preliminary clinical experience. Methods and Materials: Digital Imaging and Communications in Medicine radiotherapy (DICOM-RT) datasets from 6 T1-2 conventionally treated glottic cancer patients were used to create both conventional IMRT plans. We developed a simplified IMRT planning algorithm with three fields and limited segments. Conventional and IMRT plans were compared using generalized equivalent uniform dose and dose-volume parameters for in-field carotid arteries, target volumes, and organs at risk. We have treated 11 patients with this simplified IMRT technique. Results: Intensity-modulated radiotherapymore » consistently reduced radiation dose to the carotid arteries (p < 0.05) while maintaining the clinical target volume coverage. With conventional planning, median carotid V35, V50, and V63 were 100%, 100%, and 69.0%, respectively. With IMRT planning these decreased to 2%, 0%, and 0%, respectively (p < 0.01). Radiation planning and treatment times were similar for conventional radiotherapy and IMRT. Treatment results have been excellent thus far. Conclusions: Intensity-modulated radiotherapy significantly reduced unnecessary radiation dose to the carotid arteries compared with conventional lateral fields while maintaining clinical target volume coverage. Further experience and longer follow-up will be required to demonstrate outcomes for cancer control and carotid artery effects.« less

Loud and angry: sound intensity modulates amygdala activation to angry voices in social anxiety disorder

PubMed Central

Simon, Doerte; Becker, Michael; Mothes-Lasch, Martin; Miltner, Wolfgang H.R.

2017-01-01

Abstract Angry expressions of both voices and faces represent disorder-relevant stimuli in social anxiety disorder (SAD). Although individuals with SAD show greater amygdala activation to angry faces, previous work has failed to find comparable effects for angry voices. Here, we investigated whether voice sound-intensity, a modulator of a voice’s threat-relevance, affects brain responses to angry prosody in SAD. We used event-related functional magnetic resonance imaging to explore brain responses to voices varying in sound intensity and emotional prosody in SAD patients and healthy controls (HCs). Angry and neutral voices were presented either with normal or high sound amplitude, while participants had to decide upon the speaker’s gender. Loud vs normal voices induced greater insula activation, and angry vs neutral prosody greater orbitofrontal cortex activation in SAD as compared with HC subjects. Importantly, an interaction of sound intensity, prosody and group was found in the insula and the amygdala. In particular, the amygdala showed greater activation to loud angry voices in SAD as compared with HC subjects. This finding demonstrates a modulating role of voice sound-intensity on amygdalar hyperresponsivity to angry prosody in SAD and suggests that abnormal processing of interpersonal threat signals in amygdala extends beyond facial expressions in SAD. PMID:27651541

Symptom Induction and De-escalation in the Treatment of Panic Attacks.

ERIC Educational Resources Information Center

Dattilio, Frank M.

1990-01-01

Describes technique known as symptom induction and de-escalation for panic attacks in which goal is to reproduce the type of situation that may precipitate an attack and then to show the client how the attacks can be "turned on" as well as "turned off." (ABL)

Indicators, Predictors, and Determinants of Conflict Escalation and De-escalation. A Review of the Psychological Literature

DTIC Science & Technology

2009-05-01

des outils habituels de la psychologie parce que ces gens ne sont pratiquement jamais disponibles pour les chercheurs. Pour compenser, des méthodes...Ballard, E. J. (1983). Canadian prime ministers: Complexity in political crises. Canadian Psychology/ Psychologie Canadienne, 24, 125-129. Beasley

Bloc Concentration and Dispute Escalation among the Major Powers, 1830-1965.

ERIC Educational Resources Information Center

Stoll, Richard J.

1984-01-01

In the 1830-1914 era, when the major powers had a high level of political-military interdependence and alliance flexibility, changes in bloc concentration were a good predictor of dispute escalation. But bloc concentration had little predictive ability when this interdependence and alliance flexibility declined (1919-1965). (RM)

18 CFR Table 1 to Part 301 - Functionalization and Escalation Codes

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Functionalization and Escalation Codes 1 Table 1 to Part 301 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS FOR FEDERAL POWER MARKETING ADMINISTRATIONS AVERAGE SYSTEM COST...

18 CFR Table 1 to Part 301 - Functionalization and Escalation Codes

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Functionalization and Escalation Codes 1 Table 1 to Part 301 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS FOR FEDERAL POWER MARKETING ADMINISTRATIONS AVERAGE SYSTEM COST...

18 CFR Table 1 to Part 301 - Functionalization and Escalation Codes

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Functionalization and Escalation Codes 1 Table 1 to Part 301 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS FOR FEDERAL POWER MARKETING ADMINISTRATIONS AVERAGE SYSTEM COST...

18 CFR Table 1 to Part 301 - Functionalization and Escalation Codes

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Functionalization and Escalation Codes 1 Table 1 to Part 301 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS FOR FEDERAL POWER MARKETING ADMINISTRATIONS AVERAGE SYSTEM COST...

18 CFR Table 1 to Part 301 - Functionalization and Escalation Codes

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Functionalization and Escalation Codes 1 Table 1 to Part 301 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS FOR FEDERAL POWER MARKETING ADMINISTRATIONS AVERAGE SYSTEM COST...

Inherent smoothness of intensity patterns for intensity modulated radiation therapy generated by simultaneous projection algorithms

NASA Astrophysics Data System (ADS)

Xiao, Ying; Michalski, Darek; Censor, Yair; Galvin, James M.

2004-07-01

The efficient delivery of intensity modulated radiation therapy (IMRT) depends on finding optimized beam intensity patterns that produce dose distributions, which meet given constraints for the tumour as well as any critical organs to be spared. Many optimization algorithms that are used for beamlet-based inverse planning are susceptible to large variations of neighbouring intensities. Accurately delivering an intensity pattern with a large number of extrema can prove impossible given the mechanical limitations of standard multileaf collimator (MLC) delivery systems. In this study, we apply Cimmino's simultaneous projection algorithm to the beamlet-based inverse planning problem, modelled mathematically as a system of linear inequalities. We show that using this method allows us to arrive at a smoother intensity pattern. Including nonlinear terms in the simultaneous projection algorithm to deal with dose-volume histogram (DVH) constraints does not compromise this property from our experimental observation. The smoothness properties are compared with those from other optimization algorithms which include simulated annealing and the gradient descent method. The simultaneous property of these algorithms is ideally suited to parallel computing technologies.

Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.

PubMed

El-Khoueiry, Anthony B; Sangro, Bruno; Yau, Thomas; Crocenzi, Todd S; Kudo, Masatoshi; Hsu, Chiun; Kim, Tae-You; Choo, Su-Pin; Trojan, Jörg; Welling, Theodore H; Meyer, Tim; Kang, Yoon-Koo; Yeo, Winnie; Chopra, Akhil; Anderson, Jeffrey; Dela Cruz, Christine; Lang, Lixin; Neely, Jaclyn; Tang, Hao; Dastani, Homa B; Melero, Ignacio

2017-06-24

For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection. Previous sorafenib treatment was allowed. A dose-escalation phase was conducted at seven hospitals or academic centres in four countries or territories (USA, Spain, Hong Kong, and Singapore) and a dose-expansion phase was conducted at an additional 39 sites in 11 countries (Canada, UK, Germany, Italy, Japan, South Korea, Taiwan). At screening, eligible patients had Child-Pugh scores of 7 or less (Child-Pugh A or B7) for the dose-escalation phase and 6 or less (Child-Pugh A) for the dose-expansion phase, and an Eastern Cooperative Oncology Group performance status of 1 or less. Patients with HBV infection had to be receiving effective antiviral therapy (viral load <100 IU/mL); antiviral therapy was not required for patients with HCV infection. We excluded patients previously treated with an agent targeting T-cell costimulation or checkpoint pathways. Patients received intravenous nivolumab 0·1-10 mg/kg every 2 weeks in the dose-escalation phase (3+3 design). Nivolumab 3 mg/kg was given every 2 weeks in the dose-expansion phase to patients in four cohorts: sorafenib untreated or intolerant without viral hepatitis, sorafenib progressor without viral hepatitis, HCV infected, and HBV infected. Primary endpoints were safety and tolerability for the escalation phase and objective response rate (Response Evaluation Criteria In Solid Tumors version 1.1) for the expansion phase. This study is registered with ClinicalTrials.gov, number NCT01658878. Between Nov 26, 2012, and Aug 8, 2016, 262 eligible patients were treated (48 patients in the dose-escalation phase and 214 in the dose-expansion phase). 202 (77%) of 262 patients have completed treatment and follow-up is ongoing. During dose escalation, nivolumab showed a manageable safety profile, including acceptable tolerability. In this phase, 46 (96%) of 48 patients discontinued treatment, 42 (88%) due to disease progression. Incidence of treatment-related adverse events did not seem to be associated with dose and no maximum tolerated dose was reached. 12 (25%) of 48 patients had grade 3/4 treatment-related adverse events. Three (6%) patients had treatment-related serious adverse events (pemphigoid, adrenal insufficiency, liver disorder). 30 (63%) of 48 patients in the dose-escalation phase died (not determined to be related to nivolumab therapy). Nivolumab 3 mg/kg was chosen for dose expansion. The objective response rate was 20% (95% CI 15-26) in patients treated with nivolumab 3 mg/kg in the dose-expansion phase and 15% (95% CI 6-28) in the dose-escalation phase. Nivolumab had a manageable safety profile and no new signals were observed in patients with advanced hepatocellular carcinoma. Durable objective responses show the potential of nivolumab for treatment of advanced hepatocellular carcinoma. Bristol-Myers Squibb. Copyright © 2017 Elsevier Ltd. All rights reserved.

Magnified Neural Envelope Coding Predicts Deficits in Speech Perception in Noise.

PubMed

Millman, Rebecca E; Mattys, Sven L; Gouws, André D; Prendergast, Garreth

2017-08-09

Verbal communication in noisy backgrounds is challenging. Understanding speech in background noise that fluctuates in intensity over time is particularly difficult for hearing-impaired listeners with a sensorineural hearing loss (SNHL). The reduction in fast-acting cochlear compression associated with SNHL exaggerates the perceived fluctuations in intensity in amplitude-modulated sounds. SNHL-induced changes in the coding of amplitude-modulated sounds may have a detrimental effect on the ability of SNHL listeners to understand speech in the presence of modulated background noise. To date, direct evidence for a link between magnified envelope coding and deficits in speech identification in modulated noise has been absent. Here, magnetoencephalography was used to quantify the effects of SNHL on phase locking to the temporal envelope of modulated noise (envelope coding) in human auditory cortex. Our results show that SNHL enhances the amplitude of envelope coding in posteromedial auditory cortex, whereas it enhances the fidelity of envelope coding in posteromedial and posterolateral auditory cortex. This dissociation was more evident in the right hemisphere, demonstrating functional lateralization in enhanced envelope coding in SNHL listeners. However, enhanced envelope coding was not perceptually beneficial. Our results also show that both hearing thresholds and, to a lesser extent, magnified cortical envelope coding in left posteromedial auditory cortex predict speech identification in modulated background noise. We propose a framework in which magnified envelope coding in posteromedial auditory cortex disrupts the segregation of speech from background noise, leading to deficits in speech perception in modulated background noise. SIGNIFICANCE STATEMENT People with hearing loss struggle to follow conversations in noisy environments. Background noise that fluctuates in intensity over time poses a particular challenge. Using magnetoencephalography, we demonstrate anatomically distinct cortical representations of modulated noise in normal-hearing and hearing-impaired listeners. This work provides the first link among hearing thresholds, the amplitude of cortical representations of modulated sounds, and the ability to understand speech in modulated background noise. In light of previous work, we propose that magnified cortical representations of modulated sounds disrupt the separation of speech from modulated background noise in auditory cortex. Copyright © 2017 Millman et al.

Miniaturized High-Speed Modulated X-Ray Source

NASA Technical Reports Server (NTRS)

Gendreau, Keith C. (Inventor); Arzoumanian, Zaven (Inventor); Kenyon, Steven J. (Inventor); Spartana, Nick Salvatore (Inventor)

2015-01-01

A miniaturized high-speed modulated X-ray source (MXS) device and a method for rapidly and arbitrarily varying with time the output X-ray photon intensities and energies. The MXS device includes an ultraviolet emitter that emits ultraviolet light, a photocathode operably coupled to the ultraviolet light-emitting diode that emits electrons, an electron multiplier operably coupled to the photocathode that multiplies incident electrons, and an anode operably coupled to the electron multiplier that is configured to produce X-rays. The method for modulating MXS includes modulating an intensity of an ultraviolet emitter to emit ultraviolet light, generating electrons in response to the ultraviolet light, multiplying the electrons to become more electrons, and producing X-rays by an anode that includes a target material configured to produce X-rays in response to impact of the more electrons.

Are 50-khz calls used as play signals in the playful interactions of rats? III. The effects of devocalization on play with unfamiliar partners as juveniles and as adults.

PubMed

Kisko, Theresa M; Euston, David R; Pellis, Sergio M

2015-04-01

When playing, rats emit 50-kHz calls which may function as play signals. A previous study using devocalized rats provides support for the hypothesis that 50-kHz function to promote and maintain playful interactions (Kisko et al., 2015). However, in that study, all pairs were cage mates and familiar with each other's playful tendencies that could have attenuated the role of play signals. The present study uses unfamiliar pairs to eliminate any chance for such attenuation. Four hypotheses about how 50-kHz calls could act as play signals were tested, that (1) they maintain the playful mood of the partner, (2) they are used to locate partners, (3) they attract play partners and (4) they reduce the risk of playful encounters from escalating to serious fights. Predictions arising from the first three hypotheses, tested in juveniles, were not supported, suggesting that, for juveniles, 50-kHz calls are not facilitating playful interactions as play signals. The fourth hypothesis, however, was supported in adults, but not in juveniles, in that unfamiliar adult males were more likely to escalate playful encounters into serious fights when one partner was devocalized. These findings suggest that vocalizations at most have a minor role in juvenile play but serve a more central role in modulating adult interactions between strangers, allowing for the tactical mitigation of the risk of aggression. Copyright © 2015 Elsevier B.V. All rights reserved.

Photosynthesis under artificial light: the shift in primary and secondary metabolism

PubMed Central

Darko, Eva; Heydarizadeh, Parisa; Schoefs, Benoît; Sabzalian, Mohammad R.

2014-01-01

Providing an adequate quantity and quality of food for the escalating human population under changing climatic conditions is currently a great challenge. In outdoor cultures, sunlight provides energy (through photosynthesis) for photosynthetic organisms. They also use light quality to sense and respond to their environment. To increase the production capacity, controlled growing systems using artificial lighting have been taken into consideration. Recent development of light-emitting diode (LED) technologies presents an enormous potential for improving plant growth and making systems more sustainable. This review uses selected examples to show how LED can mimic natural light to ensure the growth and development of photosynthetic organisms, and how changes in intensity and wavelength can manipulate the plant metabolism with the aim to produce functionalized foods. PMID:24591723

An Effectiveness Trial of Contingency Management in a Felony Preadjudication Drug Court

PubMed Central

Marlowe, Douglas B; Festinger, David S; Dugosh, Karen L; Arabia, Patricia L; Kirby, Kimberly C

2008-01-01

This study evaluated a contingency management (CM) program in a drug court. Gift certificates for compliance were delivered at 4- to 6-week intervals (total value  =  $390.00). Participants in one condition earned gift certificates that escalated by $5.00 increments. Participants in a second condition began earning higher magnitude gift certificates, and the density of reinforcement was gradually decreased. No main effects of CM were detected, which appears to be attributable to a ceiling effect from the intensive contingencies already delivered in the drug court and the low density of reinforcement. Preplanned interaction analyses suggested that participants with more serious criminal backgrounds might have performed better in the CM conditions. This suggests that CM programs may be best suited for more incorrigible drug offenders. PMID:19192860

Parent Engagement in Youth Drug Prevention in Chinese Families: Advancement in Program Development and Evaluation

PubMed Central

Tsang, Sandra K. M.

2011-01-01

The escalating youth drug abuse problem in Hong Kong has attracted intense attention from the government, schools, and youth service professionals. Most preventive efforts have focused directly on positive youth development, very often through school programs delivered to secondary school students. There have been limited efforts to engage parents even though it is obvious that the family is actually the primary context of children and youth development. This paper will assert the importance of parental engagement in youth drug-prevention work, discuss some barriers in such parental involvement, present some promising local attempts and their strengths and limitations, and propose that sustained efforts are needed to build up theory-driven and evidence-based resources for Chinese communities on the subject. PMID:22194665

Mechanisms underlying intensity-dependent changes in cortical selectivity for frequency-modulated sweeps.

PubMed

Razak, K A

2012-04-01

Frequency-modulated (FM) sweeps are common components of species-specific vocalizations. The intensity of FM sweeps can cover a wide range in the natural environment, but whether intensity affects neural selectivity for FM sweeps is unclear. Bats, such as the pallid bat, which use FM sweeps for echolocation, are suited to address this issue, because the intensity of echoes will vary with target distance. In this study, FM sweep rate selectivity of pallid bat auditory cortex neurons was measured using downward sweeps at different intensities. Neurons became more selective for FM sweep rates present in the bat's echolocation calls as intensity increased. Increased selectivity resulted from stronger inhibition of responses to slower sweep rates. The timing and bandwidth of inhibition generated by frequencies on the high side of the excitatory tuning curve [sideband high-frequency inhibition (HFI)] shape rate selectivity in cortical neurons in the pallid bat. To determine whether intensity-dependent changes in FM rate selectivity were due to altered inhibition, the timing and bandwidth of HFI were quantified at multiple intensities using the two-tone inhibition paradigm. HFI arrived faster relative to excitation as sound intensity increased. The bandwidth of HFI also increased with intensity. The changes in HFI predicted intensity-dependent changes in FM rate selectivity. These data suggest that neural selectivity for a sweep parameter is not static but shifts with intensity due to changes in properties of sideband inhibition.